scholarly journals Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses

mBio ◽  
2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Judith M. White ◽  
Joshua T. Schiffer ◽  
Rachel A. Bender Ignacio ◽  
Shuang Xu ◽  
Denis Kainov ◽  
...  
Keyword(s):  
Drug Combinations ◽  
Emerging Viruses ◽  
First Line ◽  
Viral Pathogens ◽  
The World ◽  
Highly Effective

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens.

Individuality and Beyond

2019 ◽  
Author(s):  
Benedetta Zavatta
Keyword(s):  
Moral Autonomy ◽  
First Line ◽  
Philosophical Interpretation ◽  
Individual Personality ◽  
The World ◽  
Regulative Ideal ◽  
Personal Library ◽  
The Many ◽  
The Individual ◽  
The Impact

Based on an analysis of the marginal markings and annotations Nietzsche made to the works of Emerson in his personal library, the book offers a philosophical interpretation of the impact on Nietzsche’s thought of his reading of these works, a reading that began when he was a schoolboy and extended to the final years of his conscious life. The many ideas and sources of inspiration that Nietzsche drew from Emerson can be organized in terms of two main lines of thought. The first line leads in the direction of the development of the individual personality, that is, the achievement of critical thinking, moral autonomy, and original self-expression. The second line of thought is the overcoming of individuality: that is to say, the need to transcend one’s own individual—and thus by definition limited—view of the world by continually confronting and engaging with visions different from one’s own and by putting into question and debating one’s own values and certainties. The image of the strong personality that Nietzsche forms thanks to his reading of Emerson ultimately takes on the appearance of a nomadic subject who is continually passing out of themselves—that is to say, abandoning their own positions and convictions—so as to undergo a constant process of evolution. In other words, the formation of the individual personality takes on the form of a regulative ideal: a goal that can never be said to have been definitively and once and for all attained.

Pharmacogenetics of Metformin

2021 ◽  
Vol 1 (6) ◽  
pp. 123-129
Author(s):  
Alrahman Joneri
Keyword(s):  
American Diabetes Association ◽  
Glucose Utilization ◽  
Medical Condition ◽  
World Health ◽  
First Line ◽  
Glucose Levels ◽  
Normal Limits ◽  
The World ◽  
Health Organization ◽  
The Individual

Hyperglycemia is a medical condition in which an increase in glucose levels in the blood exceeds normal limits. Hyperglycemia is one of the typical signs of diabetes mellitus (DM). The World Health Organization (WHO) predicts an increase in the number of people with DM which is a global health threat. Diabetes is the leading cause of kidney failure, and the leading cause of heart disease and stroke, in adults. Metformin, which is a biguanide group, is recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes as the first-line oral therapy for DM and is the most widely used oral medication worldwide. Metformin can also increase peripheral glucose utilization and ultimately decrease the production of fatty acids and triglycerides. Some of the individual differences that underlie the variation in response to metformin.

scholarly journals 417 Phase 3 study of pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib versus pembrolizumab + lenvatinib as first-line treatment for advanced renal cell carcinoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A447-A447
Author(s):  
Toni Choueiri ◽  
Elizabeth Plimack ◽  
Thomas Powles ◽  
Martin Voss ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Antitumor Activity ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
End Points ◽  
Once Daily ◽  
Link Type ◽  
The World ◽  
First Line Treatment

BackgroundPembrolizumab + vascular endothelial growth factor (VEGF) inhibitor lenvatinib demonstrated antitumor activity as first-line treatment for advanced clear cell renal cell carcinoma (ccRCC) in phase 3 trial KEYNOTE-581/CLEAR (NCT02811861). Hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan (MK-6482) showed antitumor activity in ccRCC, and a coformulation of pembrolizumab and CTLA-4 inhibitor quavonlimab (MK-1308A) showed antitumor activity in non–small cell lung cancer. HIF-2α or CTLA-4 inhibition with PD-1 and VEGF inhibition backbone combination may provide additional benefit as first-line treatment in ccRCC. This open-label, randomized, phase 3 study (NCT04736706) will be conducted to compare novel combination therapies pembrolizumab + belzutifan + lenvatinib (arm A) and MK-1308A + lenvatinib (arm B) with pembrolizumab + lenvatinib (arm C).MethodsApproximately 1431 adults with metastatic ccRCC, measurable disease per RECIST v1.1, and Karnofsky Performance Status Scale score ≥70% who had not previously undergone systemic therapy for advanced ccRCC will be enrolled. Patients will be randomly assigned 1:1:1 to arm A (belzutifan 120 mg + lenvatinib 20 mg oral once daily + pembrolizumab 400 mg IV every 6 weeks), arm B (MK-1308A [quavonlimab 25 mg + pembrolizumab 400 mg] IV every 6 weeks and lenvatinib 20 mg oral once daily), or arm C (pembrolizumab 400 mg IV every 6 weeks + lenvatinib 20 mg oral once daily). Treatment will continue until documented disease progression, withdrawal of consent, or other discontinuation event; patients will receive pembrolizumab and MK-1308A for up to 18 cycles (approximately 2 years). Patients will be stratified by International mRCC Database Consortium (IMDC) score (favorable vs intermediate vs poor), region of the world (North America vs Western Europe vs rest of the world), and sarcomatoid features (yes vs no). Response will be assessed by CT or MRI per RECIST v1.1 by blinded independent central review (BICR) at week 12 from randomization, every 6 weeks through week 78, and every 12 weeks thereafter. Adverse events and serious adverse events will be monitored throughout the study and for 90 days after treatment. Dual primary end points are progression-free survival per RECIST v1.1 by BICR and overall survival. Primary end points will be assessed in arm A compared with arm C and in arm B compared with arm C for patients with IMDC intermediate/poor status and in all patients regardless of IMDC status. Secondary end points are objective response rate and duration of response per RECIST v1.1 by BICR, patient-reported outcomes, and safety.AcknowledgementsMedical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA,Eisai Inc., Woodcliff Lake, NJ, USA.Trial RegistrationClinicaltrials.gov, NCT04736706Ethics ApprovalThe study and the protocol were approved by the Institutional Review Board or ethics committee at each site.

When are drug combinations justified?

1980 ◽  
Vol 18 (10) ◽  
pp. 37-40
Keyword(s):  
Metabolic Disease ◽  
World Wide ◽  
Fixed Ratio ◽  
Drug Combinations ◽  
World Health ◽  
Active Ingredients ◽  
Dose Ratio ◽  
Drug Products ◽  
Branded Drug ◽  
The World

Drug combinations contain two or more active ingredients in fixed doses in a single preparation; the dose-ratio is determined by the manufacturer. Among over 240 preparations on the World Health Organisation’s model list of ‘essential’ drugs, there are only 7 drug combinations - less than 3%.1 By contrast, of more than 2, 2000 branded drug products listed in MIMS,2 nearly half are fixed-ratio combinations, although the proportion varies widely between therapeutic groups - 10% for metabolic disease, 70% for respiratory and gastro-intestinal conditions.3 More than one-third of all new drug products introduced world-wide in 1978 were combinations.4

scholarly journals nCovid-19 in 2020: From Despair to Hope

Coronaviruses ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 9-12
Author(s):  
Ravi Varala ◽  
Haribabu Bollikolla
Keyword(s):  
Side Effects ◽  
Medical Diagnosis ◽  
Drug Combinations ◽  
The World ◽  
Safe Vaccine

Outbreak mentioned in China in December 2019 has spread rapidly across 220 countries infecting more than 6.8 million people and killing nearly about 0.4 million people across the world and is declared as ‘pandemic’ by WHO. In this perspective, authors have presented a brief overview of Covid- 19 from its origin to transmission and the measures to be taken to restrict the outbreak of this evil virus. Medical diagnosis offers some promising drug combinations for treating the infected patients effectively, although with some side effects. Research is currently in progress, giving us the hope of getting a viable and safe vaccine.

Who fears to speak of politics? John Kells Ingram and hypothetical nationalism

1998 ◽  
Vol 31 (122) ◽  
pp. 202-221 ◽  
Author(s):  
G.K. Peatling
Keyword(s):  
Trinity College ◽  
Academic Career ◽  
Presidential Address ◽  
First Line ◽  
Nationalist Movement ◽  
Trinity College Dublin ◽  
The World ◽  
History Of ◽  
History Of Political Economy ◽  
One Act

John Kells Ingram was born in County Donegal in 1823. His ancestry was Scottish Presbyterian, but his grandparents had converted to Anglicanism. He was educated at Trinity College, Dublin, the most prestigious academic institution in nineteenth-century Ireland. In a brilliant academic career spanning over fifty years he proceeded to occupy a succession of chairs at the college. His published work included an important History of political economy (1888), and he delivered a significant presidential address to the economics and statistics section of the British Association for the Advancement of Science (1878). Ingram influenced, and was respected by, many contemporary social and economic thinkers in the British Isles and elsewhere. In an obituary one of Ingram’s friends exaggerated only slightly in describing him as ‘probably the best educated man in the world’. Yet contemporary perspectives on Ingram’s career were warped by one act of his youth which was to create a curious disjunction in his life. In 1843, when only nineteen years old, Ingram was a sympathiser with the nationalist Young Ireland movement. One night, stirred by the lack of regard shown for the Irish rebels of 1798 by the contemporary O’Connellite nationalist movement, he wrote a poem entitled ‘The memory of the dead’, eulogising these ‘patriots’. Apparently without much thought, Ingram submitted the poem anonymously to the Nation newspaper. It appeared in print on 1 April 1843 and, better known by its first line, ‘Who fears to speak of ’Ninety-Eight?’, became a popular Irish nationalist anthem.

scholarly journals Comparative In Vitro Activities of Torezolid (DA-7157) against Clinical Isolates of Aerobic and Anaerobic Bacteria in South Korea

2010 ◽  
Vol 54 (12) ◽  
pp. 5381-5386 ◽  
Author(s):  
Jong Hwa Yum ◽  
Sung Hak Choi ◽  
Dongeun Yong ◽  
Yunsop Chong ◽  
Weon Bin Im ◽  
...  
Keyword(s):  
South Korea ◽  
Antimicrobial Agents ◽  
Anaerobic Bacteria ◽  
Clinical Isolates ◽  
Bacterial Isolates ◽  
First Line ◽  
Gram Positive ◽  
The World ◽  
Aerobic And Anaerobic

ABSTRACT Resistance of Gram-positive pathogens to first-line antimicrobial agents has been increasing in many parts of the world. We compared the in vitro activities of torezolid with those of other antimicrobial agents, including linezolid, against clinical isolates of major aerobic and anaerobic bacteria. Torezolid had an MIC90 of ≤0.5 μg/ml for the Gram-positive bacterial isolates tested and was more potent than either linezolid or vancomycin.

scholarly journals Nonprescription drugs recommended in guidelines for common pain conditions

2020 ◽  
Vol 10 (2) ◽  
pp. 117-129 ◽  
Author(s):  
Martina Hagen ◽  
John Alchin
Keyword(s):  
Evidence Based ◽  
Nonprescription Drugs ◽  
First Line ◽  
The World ◽  
Adults And Children ◽  
Inflammatory Drugs ◽  
Health Institutions ◽  
Effective Pain Relief ◽  
The Uk ◽  
Topical Nsaids

Evidence-based pain guidelines allow recommendation of nonprescription analgesics to patients, facilitating self-care. We researched clinical practice guidelines for common conditions on websites of pain associations, societies, health institutions and organizations, PubMed, ProQuest, Embase, Google Scholar until April 2019. We wanted to determine whether there is a consensus between guidelines. From 114 identified guidelines, migraine (27) and osteoarthritis (26) have been published most around the world, while dysmenorrhea (14) is mainly discussed in developing countries. Specific recommendations to pregnant women, children and older people predominantly come from the UK and USA. We found that acetaminophen and oral nonsteroidal anti-inflammatory drugs (NSAIDs) represent first-line management across all pain conditions in adults and children. In osteoarthritis, topical NSAIDs should be considered before oral NSAIDs. This knowledge might persuade patients that using these drugs first could enable fast and effective pain relief.

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