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Rational use of drug

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https://www.readbyqxmd.com/read/28226334/prescription-opioid-abuse-in-chronic-pain-an-updated-review-of-opioid-abuse-predictors-and-strategies-to-curb-opioid-abuse-part-2
#1
Alan D Kaye, Mark R Jones, Adam M Kaye, Juan G Ripoll, Donald E Jones, Vincent Galan, Burton D Beakley, Frank Calixto, Jamie L Bolden, Richard D Urman, Laxmaiah Manchikanti
Chronic pain and prescription opioid abuse are extremely prevalent in the United States and worldwide. The consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. The risk for misuse of prescribed opioids is much higher in patients with chronic pain, especially those with concurrent substance use and /or mental health disorders. Several reasons can account for the occurrence of opioid abuse and misuse, including self-medication, use for reward, compulsive use related to addiction, and diversion for profit...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28226333/prescription-opioid-abuse-in-chronic-pain-an-updated-review-of-opioid-abuse-predictors-and-strategies-to-curb-opioid-abuse-part-1
#2
Alan D Kaye, Mark R Jones, Adam M Kaye, Juan G Ripoll, Vincent Galan, Burton D Beakley, Frank Calixto, Jamie L Bolden, Richard D Urman, Laxmaiah Manchikanti
Chronic pain and prescription opioid abuse are extremely prevalent both in this country and worldwide. Consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. Individuals with chronic pain and co-occurring substance use disorders and/or mental health disorders, are at a higher risk for misuse of prescribed opioids. Opioid abuse and misuse occurs for a variety of reasons, including self-medication, use for reward, compulsive use because of addiction, and diversion for profit...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28225601/rational-optimization-of-diphenyl-ether-binding-kinetics-to-the-enoyl-acp-reductase-fabi1-from-burkholderia-pseudomallei
#3
Carla Maya Neckles, Sandra Eltschkner, Jason Ellsworth Cummings, Maria Hirschbeck, Fereidoon Daryaee, Gopal R Bommineni, Zhuo Zhang, Lauren A Spagnuolo, Weixuan Yu, Shabnam Davoodi, Richard A Slayden, Caroline Kisker, Peter J Tonge
There is growing awareness of the link between drug-target residence time and in vivo drug activity, and there are increasing efforts to determine the molecular factors that control the lifetime of a drug-target complex. Rational alterations in drug-target residence time require knowledge of both the ground and transition states on the inhibition reaction coordinate, and we have determined the structure-kinetic relationship for 22 ethyl or hexyl substituted diphenyl ethers that are slow-binding inhibitors of bpFabI1, the enoyl-ACP reductase FabI1 from Burkholderia pseudomallei...
February 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28225177/an-irreversible-inhibitor-of-hsp72-that-unexpectedly-targets-lysine-56
#4
Jonathan Pettinger, Yann-Vaï Le Bihan, Marcella Widya, Rob L M van Montfort, Keith Jones, Matthew D Cheeseman
The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells is difficult owing to competition with the high affinity and abundance of its endogenous nucleotide substrates. We hypothesized this could be overcome using a cysteine-targeted irreversible inhibitor. Using rational design, we adapted a validated 8-N-benzyladenosine ligand for covalent bond formation and confirmed targeted irreversible inhibition...
February 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28224422/satisfaction-of-village-doctors-with-the-township-and-village-health-services-integration-policy-in-the-western-minority-inhabited-areas-of-china
#5
Da Feng, Liang Zhang, Yuan-Xi Xiang, Dong-Lan Zhang, Ruo-Xi Wang, Shang-Feng Tang, Hang Fu, Bo-Yang Li
Township and Village Health Services Integration Management (TVHSIM) is an essential form of China's two-tiered health service integration plan at the township and village level. Its main purpose, also one of the target goals in China's new healthcare reform, is to gradually integrate rural health services and appropriately allocate rural health resources. This study aims to assess the village doctors' satisfaction with the TVHSIM and provide scientific base to further improve TVHSIM. A cross-sectional study was carried out in which 162 village doctors from Qinghai, Inner Mongolia and Xinjiang in western China were interviewed...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28223846/prospect-of-the-use-of-checkpoint-inhibitors-in-hepatocellular-cancer-treatments
#6
REVIEW
Ali Raufi, Maria Tria Tirona
Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%-3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28223781/factors-influencing-the-exit-knowledge-of-patients-for-dispensed-drugs-at-outpatient-pharmacy-of-hiwot-fana-specialized-university-hospital-eastern-ethiopia
#7
Nigatu Hirko, Dumessa Edessa
BACKGROUND: A satisfactory counseling process between the patient and pharmacist is critical for rational use of dispensed drug(s) and is highly influenced by many factors including the experience of pharmacist in dispensing process. To improve patients' knowledge of dispensed drugs, it is necessary to understand the factors that optimize a pharmacist interaction with a patient in each activity of the dispensing process. Therefore, the aim of this study was to identify the pharmacist and patient factors that influence knowledge of dispensed drugs by ambulatory patients at Hiwot Fana Specialized University Hospital, Harar, Ethiopia...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28220863/engineering-botulinum-neurotoxin-c1-as-a-molecular-vehicle-for-intra-neuronal-drug-delivery
#8
Edwin J Vazquez-Cintron, Phillip H Beske, Luis Tenezaca, Bao Q Tran, Jonathan M Oyler, Elliot J Glotfelty, Christopher A Angeles, Aurelia Syngkon, Jean Mukherjee, Suzanne R Kalb, Philip A Band, Patrick M McNutt, Charles B Shoemaker, Konstantin Ichtchenko
Botulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219852/linear-correlation-between-rheological-mechanical-and-mucoadhesive-properties-of-polycarbophil-polymer-blends-for-biomedical-applications
#9
Sabrina Barbosa De Souza Ferreira, Jéssica Bassi Da Silva, Fernanda Belincanta Borghi-Pangoni, Mariana Volpato Junqueira, Marcos Luciano Bruschi
Polycarbophil is widely used in a variety of pharmaceutical formulations, mainly for their strong ability to adhere to the epithelial and mucous barriers (bio/mucoadhesion). On the other hand, its association with the thermoresponsive polymer (poloxamer 407) has been poorly explored. This work investigates the rheological, mechanical and mucoadhesive properties of polymer blends containing polycarbophil and poloxamer 407, in order to select the best formulations for biomedical and pharmaceutical applications...
February 14, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28217544/assessment-of-knowledge-attitude-and-practices-on-fixed-dose-combinations-among-postgraduate-dental-students
#10
Narayana R Vinnakota, V Krishna, V Viswanath, Zaheer Ahmed, Kamal S Shaik, Naveen K Boppana
AIM: To assess the knowledge, attitude, and practices of fixed dose combination drugs among postgraduate dental students. MATERIALS AND METHODS: A cross-sectional study was carried out among postgraduate dental students of dental colleges in coastal Andhra Pradesh. Three colleges were randomly selected and students of all the three years were included. Data was collected from the specialities of oral medicine and radiology, oral surgery, endodontics, pedodontics, periodontics, and public health dentistry...
December 2016: Journal of International Society of Preventive & Community Dentistry
https://www.readbyqxmd.com/read/28217527/vascular-legacy-hope-advances-to-empa-reg-and-leader-a-surprising-similarity
#11
Sanjay Kalra, Rakesh Sahay
Recently reported cardiovascular outcome studies on empagliflozin (EMPA-REG) and liraglutide (LEADER) have spurred interest in this field of diabetology. This commentary compares and contrasts these studies with two equally important outcome trials conducted using blood pressure lowering agents. A comparison with MICROHOPE (using ramipril) and ADVANCE (using perindopril + indapamide) blood pressure arms throws up interesting facts. The degree of blood pressure lowering, dissociation between cardiovascular and cerebrovascular benefits, and discordance between renal and retinal outcomes are surprisingly similar in these trials, conducted using disparate molecules...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#12
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/28213817/breakthrough-cancer-pain-and-rational-drug-use
#13
Juan Manuel Núñez Olarte
Recent data indicate that there are large disparities in the use of opioid analgesics to control breakthrough cancer pain (BTcP) in Europe and worldwide. While it is clear that affordability is a key factor, it is certainly not the only one, and other factors, such as cultural differences and overall awareness, are undoubtedly responsible. More work remains to be done to overcome barriers in the use of these medications when warranted. When prescribing a medication for BTcP, it must be considered that its time profile is different from chronic persistent pain...
February 18, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care 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
#14
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/28210763/artemisinin-and-its-derivatives-in-cancer-therapy-status-of-progress-mechanism-of-action-and-future-perspectives
#15
REVIEW
Archana Bhaw-Luximon, Dhanjay Jhurry
Since the late 1990s, there has been rapid multiplication of data on the anti-cancer properties of artemisinins. This article reviews the status of progress of artemisinin and its derivatives as anti-cancer agents in clinical trials, case reports, and in vitro/in vivo studies. Particular attention is laid on the combinations of artemisinins and synthetic chemodrugs to enhance the latter's efficacy. An attempt is here made to rationalize the synergistic effects of a few common anti-cancer drugs of the anthracycline, taxane, anti-metabolite, and platinum-based drug families...
February 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28208215/nanoparticle-delivery-systems-general-approaches-and-their-implementation-in-multiple-myeloma
#16
REVIEW
Pilar de la Puente, Abdel Kareem Azab
Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates greater than 90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects. Traditional chemotherapy has shown several disadvantages such as lack of targeting capabilities, systemic toxicity and side effects; low therapeutic index, as well as, most anticancer drugs have poor water solubility...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28206763/rational-design-of-a-polymer-with-robust-efficacy-for-intracellular-protein-and-peptide-delivery
#17
Hong Chang, Jia Lv, Xin Gao, Xing Wang, Hui Wang, Hui Chen, Xu He, Lei Li, Yiyun Cheng
The efficient delivery of biopharmaceutical drugs such as proteins and peptides into the cytosol of target cells poses substantial challenges owing to their large size and susceptibility to degradation. Current protein delivery vehicles have limitations such as the need for protein modification, insufficient delivery of large-size proteins or small peptides, and loss of protein function after the delivery. Here, we adopted a rational approach to design a polymer with robust efficacy for intracellular protein and peptide delivery...
February 20, 2017: Nano Letters
https://www.readbyqxmd.com/read/28202514/mcl-1-degradation-is-required-for-targeted-therapeutics-to-eradicate-colon-cancer-cells
#18
Jingshan Tong, Peng Wang, Shuai Tan, Dongshi Chen, Zaneta Nikolovska-Coleska, Fangdong Zou, Jian Yu, Lin Zhang
The Bcl-2 family protein Mcl-1 is often degraded in cancer cells subjected to effective therapeutic treatment, and defective Mcl-1 degradation has been associated with intrinsic and acquired drug resistance. However, a causal relationship between Mcl-1 degradation and anticancer drug responses has not been directly established, especially in solid tumor cells where Mcl-1 inhibition alone is insufficient to trigger cell death. In this study, we present evidence that Mcl-1 participates directly in determining effective therapeutic responses in colon cancer cells...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28195463/target-elucidation-by-co-crystal-structures-of-nadh-ubiquinone-oxidoreductase-of-plasmodium-falciparum-pfndh2-with-small-molecule-to-eliminate-drug-resistant-malaria
#19
Yiqing Yang, You Yu, Xiaolu Li, Jing Li, Yue Wu, Jie Yu, Jingpeng Ge, Zhenghui Huang, Lubin Jiang, Yu Rao, Maojun Yang
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new anti-malarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for anti-malarial drug development. However, the absence of structural information of PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH- and RYL-552 (a new inhibitor)-bound states...
February 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28193899/structure-of-a-lipid-a-phosphoethanolamine-transferase-suggests-how-conformational-changes-govern-substrate-binding
#20
Anandhi Anandan, Genevieve L Evans, Karmen Condic-Jurkic, Megan L O'Mara, Constance M John, Nancy J Phillips, Gary A Jarvis, Siobhan S Wills, Keith A Stubbs, Isabel Moraes, Charlene M Kahler, Alice Vrielink
Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4' headgroup positions by phosphoethanolamine transferases...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
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