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Rational use of medicine

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https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#1
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28212290/defining-clinical-response-criteria-and-early-response-criteria-for-precision-oncology-current-state-of-the-art-and-future-perspectives
#2
Vivek Subbiah, Hubert H Chuang, Dhiraj Gambhire, Kalevi Kairemo
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016...
February 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/28187802/critical-care-management-of-traumatic-brain-injury
#3
D K Menon, A Ercole
Traumatic brain injury (TBI) is a growing global problem, which is responsible for a substantial burden of disability and death, and which generates substantial healthcare costs. High-quality intensive care can save lives and improve the quality of outcome. TBI is extremely heterogeneous in terms of clinical presentation, pathophysiology, and outcome. Current approaches to the critical care management of TBI are not underpinned by high-quality evidence, and many of the current therapies in use have not shown benefit in randomized control trials...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28185714/choosing-wisely-the-top-5-recommendations-from-the-italian-panel-of-the-national-guidelines-for-the-management-of-acute-pharyngitis-in-children
#4
Elena Chiappini, Barbara Bortone, Giuseppe Di Mauro, Susanna Esposito, Luisa Galli, Massimo Landi, Andrea Novelli, Paola Marchisio, Gian Luigi Marseglia, Nicola Principi, Maurizio de Martino
PURPOSE: With the aim to reduce waste in the health care system and avoid risks associated with unnecessary treatment, the Italian Panel of the National Guidelines for the Management of Acute Pharyngitis in Children joined the Choosing Wisely initiative. METHODS: An ad hoc Choosing Wisely task force was selected to develop a candidate list of items for the top-5 list on pharyngitis medicine. Through a process of literature review and consensus, the final list of 5 items was chosen...
February 6, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28174251/a-process-engineering-approach-to-increase-organoid-yield
#5
Natasha Arora, Jasmin Imran Alsous, Jacob W Guggenheim, Michael Mak, Jorge Munera, James M Wells, Roger D Kamm, H Harry Asada, Stanislav Y Shvartsman, Linda G Griffith
Temporal manipulation of the in vitro environment and growth factors can direct differentiation of human pluripotent stem cells into organoids, aggregates with multiple tissue-specific cell types and three-dimensional structure mimicking native organs. A mechanistic understanding of early organoid formation is essential for improving the robustness of these methods, which is necessary prior to use in drug development and regenerative medicine. We investigated intestinal organoid emergence, focusing on measurable parameters of hindgut spheroids, the intermediate step between definitive endoderm and mature organoids...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28164761/mitogen-activated-protein-kinase-mapk-interacting-kinases-1-and-2-mnk1-and-mnk2-as-targets-for-cancer-therapy-recent-progress-in-the-development-of-mnk-inhibitors
#6
Agnieszka Dreas, Maciej Mikulski, Mariusz Milik, Charles-Henry Fabritius, Krzysztof Brzózka, Tomasz Rzymski
BACKGROUND: MNK1 and MNK2 are MAP kinase-interacting serine/threonine kinases, which are activated by RAS and MAPK signaling pathways and are involved in regulation of protein translation. Both kinases phosphorylate translation initiation factor eIF4E on a conserved serine 209. Overactivated eIF4E can act as an oncogene and contribute to the transformation both in vitro and in vivo and is highly expressed in diverse types of cancer. Interestingly, knockout mice that lack both Mnk1 and Mnk2 do not have any apparent phenotype...
February 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28164359/off-label-drug-use-in-oncology-a-systematic-review-of-literature
#7
REVIEW
M M Saiyed, P S Ong, L Chew
WHAT IS KNOWN AND OBJECTIVE: The off-label use of medicines is widespread in several diseases. This type of prescribing practice is particularly more acute in oncology. However, the suitability of anticancer medications for off-label use remains an issue of controversy, due to uncertainty around the clinical benefits and potential toxicities, limited evidence to support clinical decision-making, increased out-of-pocket costs for patients and ethical concerns around the lack of informed consent...
February 5, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28157293/a-whole-cell-based-assay-to-evaluate-structure-permeation-relationships-for-carbapenem-passage-through-the-pseudomonas-aeruginosa-porin-oprd
#8
Ramkumar Iyer, Mark A Sylvester, Camilo Velez-Vega, Ruben Tommasi, Thomas F Durand-Reville, Alita A Miller
The global emergence of antibiotic resistance, especially in Gram-negative bacteria, is an urgent threat to public health. Discovery of novel classes of antibiotics with activity against these pathogens has been impeded by a fundamental lack of understanding of the molecular drivers underlying small molecule uptake. Although it is well-known that outer membrane porins represent the main route of entry for small, hydrophilic molecules across the Gram-negative cell envelope, the structure-permeation relationship for porin passage has yet to be defined...
February 3, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28156441/strategy-of-using-herbal-extract-preparations-for-stage-iv-cancer-in-palliative-care-an-enhanced-and-maintenance-therapy
#9
Zhang Lingyan, Zhou Xiaoxia, Yin Weihua, Zhang Xiulian, Liu Hong, Duan Xiaopeng, Yu Cui, Luo Xiaolu, Zhong Qingfeng, Zhao Fen, Li Xianyong
: 89 Background: Palliative care is focused and seems as rationally anti-cancer way that have low systemic toxicity and acceptable effectiveness for stage IV cancer, especially herbal extracted medicines, which can regulate tumor microenviroment and body immune system. Our previous lab studies have indicated that TGF-beta, EGF, VEGF, IL-10 cytokines expression and mico-vessel density can be downgraded in tumor microenviroment by herbal extract preparation from Ginseng, Herba Agrimonia, Hairyvein and Arginine etc...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28155846/rationalizing-the-permeation-of-polar-antibiotics-into-gram-negative-bacteria
#10
Mariano Andrea Scorciapino, Silvia Acosta-Gutierrez, Dehbia Benkerrou, Tommaso D'Agostino, Giuliano Malloci, Susruta Samanta, Igor Bodrenko, Matteo Ceccarelli
The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds...
March 22, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28154808/patient-derived-xenograft-models-of-non-small-cell-lung-cancer-and-their-potential-utility-in-personalized-medicine
#11
Katherine M Morgan, Gregory M Riedlinger, Jeffrey Rosenfeld, Shridar Ganesan, Sharon R Pine
Traditional preclinical studies of cancer therapeutics have relied on the use of established human cell lines that have been adapted to grow in the laboratory and, therefore, may deviate from the cancer they were meant to represent. With the emphasis of cancer drug development shifting from non-specific cytotoxic agents to rationally designed molecularly targeted therapies or immunotherapy comes the need for better models with predictive value regarding therapeutic activity and response in clinical trials. Recently, the diversity and accessibility of immunodeficient mouse strains has greatly enhanced the production and utility of patient-derived xenograft (PDX) models for many tumor types, including non-small cell lung cancer (NSCLC)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28153094/a-synthetic-biology-inspired-therapeutic-strategy-for-targeting-and-treating-hepatogenous-diabetes
#12
Shuai Xue, Jianli Yin, Jiawei Shao, Yuanhuan Yu, Linfeng Yang, Yidan Wang, Mingqi Xie, Martin Fussenegger, Haifeng Ye
Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28149832/critical-analysis-of-cardiovascular-and-central-nervous-system-fixed-dose-combinations-available-in-indian-market
#13
Krunal Prajapati, Samidh Shah, Mira Desai
INTRODUCTION: Fixed Dose Combinations (FDCs) are being increasingly used to improve compliance and achieve greater benefits of the two or more active ingredients given together than the corresponding individual drug components given separately. AIM: To analyse the rationality of Cardiovascular (CV) and Central Nervous System (CNS) FDCs available in Indian market. MATERIALS AND METHODS: CVS and CNS FDCs, enlisted in Indian Drug Review, 2014, were analysed by a pretested validated eight point criteria tool...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28137238/a-practical-guide-to-molecular-docking-and-homology-modelling-for-medicinal-chemists
#14
Anna E Lohning, Stephan M Levonis, Billy Williams-Noonan, Stephanie S Schweiker
Elucidating details of the relationship between molecular structure and a particular biological end point is essential for successful rationally-based drug discovery. Molecular docking is a widely accepted tool for lead identification however navigating the intricacies of the software can be daunting. Our objective was therefore to provide a step-by-step guide for those interested in incorporating contemporary basic molecular docking and homology modelling into their design strategy. Three molecular docking programs, AutoDock4, SwissDock and Surflex-Dock, were compared in the context of a case study where a set of steroidal and non-steroidal ligands were docked into the human androgen receptor (hAR) using both rigid and flexible target atoms...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28131572/understanding-veterinarians-prescribing-decisions-on-antibiotic-dry-cow-therapy
#15
H M Higgins, S E Golding, J Mouncey, I Nanjiani, A J C Cook
In the United Kingdom, blanket antibiotic dry cow therapy (BDCT) is commonly prescribed. An alternate strategy is selective dry cow therapy (SDCT) whereby a teat sealant is given instead of an antibiotic to cows with a low probability of infection. Switching from BDCT to SDCT can significantly reduce antibiotic use. The aims of this study were to explore how veterinarians (vets) rationalized their prescribing decisions for mammary treatments at drying off, and the barriers and motivators they perceived to implementing SDCT...
January 25, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28131024/-too-much-medicine-insights-and-explanations-from-economic-theory-and-research
#16
Martin Hensher, John Tisdell, Craig Zimitat
Increasing attention has been paid in recent years to the problem of "too much medicine", whereby patients receive unnecessary investigations and treatments providing them with little or no benefit, but which expose them to risks of harm. Despite this phenomenon potentially constituting an inefficient use of health care resources, it has received limited direct attention from health economists. This paper considers "too much medicine" as a form of overconsumption, drawing on research from health economics, behavioural economics and ecological economics to identify possible explanations for and drivers of overconsumption...
January 18, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28122866/targeting-alk-precision-medicine-takes-on-drug-resistance
#17
REVIEW
Jessica J Lin, Gregory J Riely, Alice T Shaw
: Anaplastic lymphoma kinase (ALK) is a validated molecular target in several ALK-rearranged malignancies, including non-small cell lung cancer. However, the clinical benefit of targeting ALK using tyrosine kinase inhibitors (TKI) is almost universally limited by the emergence of drug resistance. Diverse mechanisms of resistance to ALK TKIs have now been discovered, and these basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic...
February 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28118502/towards-rational-evidence-based-and-clinically-relevant-measures-to-determine-improvement-following-treatment-for-alcohol-use-disorder
#18
Bankole A Johnson
This interesting paper by Witkiewitz and colleagues (Witkiewitz et al. 2017) calls for the need to create a more comprehensive scale to acknowledge and measure the naturally fluctuating levels of drinking among patients. As such, there is a dire need to unify, under a common instrument, a clinically meaningful endpoint measure to determine the efficacy of treatment for alcohol use disorder (AUD) for both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Such a homology would have the advantage that any treatment found efficacious in either of these influential and pioneering domains would be applicable to the other...
January 24, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28115991/the-impact-of-economic-rationalization-prioritization-and-rationing-on-job-satisfaction-motivation-and-team-cohesion-in-hospitals-a-survey-among-retired-physician-executives-in-germany
#19
Joerg Schnoor, Elmar Braehler, Mohamed Ghanem, Christoph E Heyde
BACKGROUND: The growing economization of the health care system and implication of market principles in the medical field have risen new and serious questions on the meaning of the medical profession, the doctor-patient relationship and the orientation of medicine itself. The impact of the dynamic clinical structures on the doctor-doctor and the doctor-patient interaction appear even unpredictable. Therefore, the impact of market-based methods, i.e. rationalization, prioritization and rationing, on job satisfaction, motivation and team cohesion should be quantified...
2017: Patient Safety in Surgery
https://www.readbyqxmd.com/read/28112836/amino-acids-and-peptide-based-supramolecular-hydrogels-for-three-dimensional-cell-culture
#20
REVIEW
Xiao-Qiu Dou, Chuan-Liang Feng
Supramolecular hydrogels assembled from amino acids and peptide-derived hydrogelators have shown great potential as biomimetic three-dimensional (3D) extracellular matrices because of their merits over conventional polymeric hydrogels, such as non-covalent or physical interactions, controllable self-assembly, and biocompatibility. These merits enable hydrogels to be made not only by using external stimuli, but also under physiological conditions by rationally designing gelator structures, as well as in situ encapsulation of cells into hydrogels for 3D culture...
January 23, 2017: Advanced Materials
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