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Definition of therapeutic effect

Marc Evans, Roopa Mehta, Jens Gundgaard, Barrie Chubb
BACKGROUND: Understanding which therapeutic innovations in diabetes represent the best value requires rigorous economic evaluation. Data from randomised controlled trials and observational studies indicate that insulin degludec has a hypoglycemia advantage versus insulin glargine 100 units/mL (glargine U100), the most widely prescribed basal insulin analogue in the UK. This analysis was done to more rigorously assess cost-effectiveness in a UK setting. METHODS: Data from two double-blinded, randomised, two-period crossover trials in type 1 (SWITCH 1) and type 2 (SWITCH 2) diabetes mellitus were used to assess the cost-effectiveness of degludec vs...
August 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Pamela Kaiser, Daniel P Kohen, Melanie L Brown, Rebecca L Kajander, Andrew J Barnes
While pediatric integrative medicine (PIM) emphasizes an "evidence-based practice using multiple therapeutic modalities"; paradoxically, literature reviews examining the prevalence and/or efficacy of such mind⁻body approaches often address PIM modalities separately. Such contributions are relevant, yet documentation of how to deliver combined complementary approaches in children and youth are scarce. Nevertheless, integrative practitioners in clinical practice routinely mix approaches to meet the individual needs of each patient...
August 7, 2018: Children
Masaki Tokutome, Tetsuya Matoba, Yasuhiro Nakano, Arihide Okahara, Masaki Fujiwara, Jun-Ichiro Koga, Kaku Nakano, Hiroyuki Tsutsui, Kensuke Egashira
Aims: Monocyte-mediated inflammation is a major mechanism underlying myocardial ischemia-reperfusion (IR) injury and the healing process after acute myocardial infarction (AMI). However, no definitive anti-inflammatory therapies have been developed for clinical use. Pioglitazone, a peroxisome proliferator-activated receptor (PPAR)γ agonist, has unique anti-inflammatory effects on monocytes/macrophages. Here, we tested the hypothesis that nanoparticle-mediated targeting of pioglitazone to monocytes/macrophages ameliorates IR injury and cardiac remodeling in preclinical animal models...
August 3, 2018: Cardiovascular Research
Takeshi Hatanaka, Hirotaka Arai, Satoru Kakizaki
Transcatheter arterial chemoembolization (TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma (HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) guidelines. Recently, balloon-occluded TACE (B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion (LE) accumulation in HCC nodules...
July 27, 2018: World Journal of Hepatology
Anja Seckinger, Jens Hillengass, Martina Emde, Susanne Beck, Christoph Kimmich, Tobias Dittrich, Michael Hundemer, Anna Jauch, Ute Hegenbart, Marc-Steffen Raab, Anthony D Ho, Stefan Schönland, Dirk Hose
Monoclonal antibodies against the cell surface antigen CD38, e.g., isatuximab, daratumumab, or Mor202, have entered the therapeutic armamentarium in multiple myeloma due to single agent overall response rates of 29 vs. 36 vs. 31%, effectivity in combination regimen, e.g., with lenalidomide or bortezomib plus dexamethasone, and tolerable side effects. Despite clinical use, many questions remain. In this manuscript, we address three of these: first, upfront CD38 target-expression in AL-amyloidosis, monoclonal gammopathy of unknown significance (MGUS), asymptomatic, symptomatic, and relapsed multiple myeloma...
2018: Frontiers in Immunology
Anne Baudry, Benoit Schneider, Jean-Marie Launay, Odile Kellermann
Genetic and pharmacological studies provided evidence that serotonin (5-HT) is an important signaling molecule for the development and the maintenance of mineralized tissues. However, how 5-HT takes part to the homeostasis of teeth and bone remains elusive. In the dental field, a major breakthrough comes from the identification of 5-HT but also dopamine (DA) as "damage" signals necessary for stem cell-based tooth repair. Pulpal stem cells express the overall functions of 5-HT and DA neurons including a definite set of functional 5-HT/DA receptors that render cells responsive for circulating bioamines...
August 2, 2018: Biochimie
Christian Iorio-Morin, Charles Touchette, Mathieu Lévesque, Khaled Effendi, David Fortin, David Mathieu
Chronic subdural hematoma (cSDH) is a frequent yet poorly studied entity. Patients with cSDH are increasingly using antithrombotic medication, are now older, and present with a variety of clinical symptoms, including incidental discoveries. Despite this increasing complexity, management has remained roughly unchanged since the late 1990s. We review here the state of cSDH research under way at Université de Sherbrooke and around the world with a focus on studies addressing specific gaps in the current evidence base...
August 15, 2018: Journal of Neurotrauma
V Schächinger, H M Hoffmeister, M A Weber, C Stellbrink
Increasing complexity and new highly differentiated therapeutic procedures in cardiology result in a need for additional training beyond cardiology board certification. The German Cardiac Society therefore developed a variety of certifications of educational curricula and definition of specialized centers. Standardization and structuring in education and patient treatment, as defined by certifications may be helpful; however, introduction of certification can have serious consequences for hospital structure, the side effects of which may impair quality of treatment for individual patients...
August 2, 2018: Herz
Emmanuel Maheu, Raveendhara R Bannuru, Gabriel Herrero-Beaumont, Fadoua Allali, Hervé Bard, Alberto Migliore
OBJECTIVES: There is a discrepancy between evidence in support of the widespread use of intra-articular hyaluronic acid (IAHA) to treat knee osteoarthritis (OA) in clinical practice, and the often discordant recommendations from multiple international guideline committees, which requires further investigation. METHODS: We conducted a literature review to determine the strength of evidence in support of the efficacy and safety of IAHA, from randomized controlled trials and meta-analyses...
June 19, 2018: Seminars in Arthritis and Rheumatism
Alexandra M Dainis, Euan A Ashley
Precision medicine strives to delineate disease using multiple data sources-from genomics to digital health metrics-in order to be more precise and accurate in our diagnoses, definitions, and treatments of disease subtypes. By defining disease at a deeper level, we can treat patients based on an understanding of the molecular underpinnings of their presentations, rather than grouping patients into broad categories with one-size-fits-all treatments. In this review, the authors examine how precision medicine, specifically that surrounding genetic testing and genetic therapeutics, has begun to make strides in both common and rare cardiovascular diseases in the clinic and the laboratory, and how these advances are beginning to enable us to more effectively define risk, diagnose disease, and deliver therapeutics for each individual patient...
April 2018: JACC. Basic to Translational Science
Ragy R Girgis, Anthony W Zoghbi, Daniel C Javitt, Jeffrey A Lieberman
Since the discovery of chlorpromazine in the 1950's, antipsychotic drugs have been the cornerstone of treatment of schizophrenia, and all attenuate dopamine transmission at the dopamine-2 receptor. Drug development for schizophrenia since that time has led to improvements in side effects and tolerability, and limited improvements in efficacy, with the exception of clozapine. However, the reasons for clozapine's greater efficacy remain unclear, despite the great efforts and resources invested therewith. We performed a comprehensive review of the literature to determine the fate of previously tested, non-dopamine-2 receptor experimental treatments...
July 21, 2018: Journal of Psychiatric Research
Byoung Wook Bang, Don Haeng Lee, Hyung Kil Kim, Kye Sook Kwon, Yong Woon Shin, Su Jin Hong, Jong Ho Moon
BACKGROUND: Endoscopically applicable hemostatic agents have been demonstrated to have high initial hemostasis rates in cases of upper gastrointestinal bleeding (UGIB). AIMS: The authors developed a new hemostatic powder (CEGP-003) and evaluated its hemostatic and ulcer healing effects in UGIB. METHODS: Patients with peptic ulcer or post-endoscopic resection bleeding were randomly assigned to be treated by epinephrine injection or CEGP-003 spray...
July 27, 2018: Digestive Diseases and Sciences
Gunan Li, Kangwen Cheng, Zhenguo Zhao, Jian Wang, Weiming Zhu, Jieshou Li
OBJECTIVE: To summarize the application of staged ileostomy and closure operation combined with nutritional support therapy in the treatment of chronic radiation intestinal injury(CRII). METHODS: Clinical data of patients with definite radiation history and pathological diagnosis of CRII receiving treatment at Department of General Surgery, Jinling Hospital from January 2012 to December 2016 were retrospectively analyzed. Patients who were diagnosed with tumor recurrence during operation or by postoperative pathology were excluded...
July 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Petra I Lorenzo, Nadia Cobo-Vuilleumier, Benoit R Gauthier
The high prevalence of diabetes mellitus (DM) in our society, together with the fact that current treatments are only palliative and do not prevent the development of life threatening side effects, highlights the urgent need for novel therapies targeting the root cause of the disease. Independent of the etiology of DM, the definitive therapeutic approach will imply the restitution of an adequate functional β-cell mass capable of compensating for the insulin demand of the organism. The recent demonstration of heterogeneity within the islets as well as their innate plasticity has encouraged the development of studies aiming at potentiation of the regenerative capacity of islets...
July 23, 2018: Current Opinion in Pharmacology
Xiaolan Feng, Yin Shi, Lifen Xie, Kun Zhang, Xiaobing Wang, Quanhong Liu, Pan Wang
A photosensitizer with high phototoxicity, low dark toxicity, and good water solubility is crucial for effective photodynamic therapy (PDT). In this study, a novel class of porphyrin-based water-soluble derivative and its isomer, named photohexer-1 (P-1) and photohexer-2 (P-2), were synthesized and investigated for anticancer activity. Both the isomers, P-1 and P-2 could be utilized as potential sensitizers for PDT not only owing to their definite constituents but predominantly due to their good absorption in the phototherapeutic window and high generation of intracellular ROS...
July 26, 2018: Journal of Medicinal Chemistry
Francesca Monteleone, Simona Taverna, Riccardo Alessandro, Simona Fontana
BACKGROUND: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, resulting from the t(9;22) chromosomal translocation. Imatinib (gleevec, STI-571) is a selective inhibitor of BCR-ABL activity highly effective in the treatment of CML. However, even though almost all CML patients respond to treatment with imatinib or third generation inhibitors, these drugs are not curative and need to be taken indefinitely or until patients become resistant...
July 25, 2018: Journal of Experimental & Clinical Cancer Research: CR
Sunwen Chou, Ronald J Ercolani, Katayoun Derakhchan
The human cytomegalovirus (CMV) UL97 kinase inhibitor maribavir is in Phase III clinical trials as antiviral therapy, including use for infections refractory or resistant to standard therapy. To assess its activity in combination with approved and experimental CMV antivirals, and with the mTor inhibitor rapamycin (sirolimus), drug effects were tested by in vitro checkerboard assays and the data were analyzed using a three dimensional model based on an independent effects definition of additive interactions...
September 2018: Antiviral Research
Louise Clare Brown, Hashim U Ahmed, Rita Faria, Ahmed El-Shater Bosaily, Rhian Gabe, Richard S Kaplan, Mahesh Parmar, Yolanda Collaco-Moraes, Katie Ward, Richard Graham Hindley, Alex Freeman, Alexander Kirkham, Robert Oldroyd, Chris Parker, Simon Bott, Nick Burns-Cox, Tim Dudderidge, Maneesh Ghei, Alastair Henderson, Rajendra Persad, Derek J Rosario, Iqbal Shergill, Mathias Winkler, Marta Soares, Eldon Spackman, Mark Sculpher, Mark Emberton
BACKGROUND: Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy. OBJECTIVES: To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway...
July 2018: Health Technology Assessment: HTA
Yuichi Kubota, Hidetoshi Nakamoto, Satoshi Egawa, Takakazu Kawamata
Background: Continuous electroencephalogram (CEEG) monitoring is increasingly being used for brain monitoring in neurocritical care setting. This is because of the proven effectiveness of CEEG in diagnosing nonconvulsive status epilepticus (NCSE) as a cause of unexplained consciousness disorder. CEEG has been demonstrated to be effective in determining the response to, and outcome of, NCSE treatment. Main body: In this review article, the authors described the indication and methods of CEEG and diagnosis based on EEG pattern...
2018: Journal of Intensive Care
Frank T Stümpel, Juliane Stein, Kirsten Himmler, Beatrix Scholz, Matthias D Seidl, Boris V Skryabin, Frank U Müller
Background: Atrial fibrillation (AF) is a significant cause of morbidity and mortality with foreseeably increasing prevalence. While large animal models of the disease are well established but resource intensive, transgenic AF mouse models are not yet widely used to develop or validate novel therapeutics for AF. Hemizygous mice with a cardiomyocyte-specific overexpression of the human cAMP response element modulator (CREM) isoform IbΔC-X spontaneously develop AF on grounds of an arrhythmogenic substrate consisting of alterations in structure, conduction, and calcium handling...
2018: Frontiers in Pharmacology
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