scholarly journals Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1092
Author(s):  
Rami A. Al-Horani ◽  
Srabani Kar
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Clinical Investigation ◽  
Early Stage ◽  
Health Care Systems ◽  
Viral Life Cycle ◽  
Chemical Structures ◽  
Care Systems ◽  
Post Entry ◽  
Potential Therapeutics

The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.

scholarly journals Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials

2020 ◽  
Vol 21 (15) ◽  
pp. 5224 ◽  
Author(s):  
Rami A. Al-Horani ◽  
Srabani Kar ◽  
Kholoud F. Aliter
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Early Stage ◽  
Health Care Systems ◽  
Viral Life Cycle ◽  
Sulfated Polysaccharides ◽  
Angiotensin Converting Enzyme 2 ◽  
Care Systems ◽  
Cycle Structures ◽  
Potential Therapeutics

The ongoing pandemic of coronavirus disease-2019 (COVID-19) is being caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease continues to present significant challenges to the health care systems around the world. This is primarily because of the lack of vaccines to protect against the infection and the lack of highly effective therapeutics to prevent and/or treat the illness. Nevertheless, researchers have swiftly responded to the pandemic by advancing old and new potential therapeutics into clinical trials. In this review, we summarize potential anti-COVID-19 therapeutics that block the early stage of the viral life cycle. The review presents the structures, mechanisms, and reported results of clinical trials of potential therapeutics that have been listed in clinicaltrials.gov. Given the fact that some of these therapeutics are multi-acting molecules, other relevant mechanisms will also be described. The reviewed therapeutics include small molecules and macromolecules of sulfated polysaccharides, polypeptides, and monoclonal antibodies. The potential therapeutics target viral and/or host proteins or processes that facilitate the early stage of the viral infection. Frequent targets are the viral spike protein, the host angiotensin converting enzyme 2, the host transmembrane protease serine 2, and clathrin-mediated endocytosis process. Overall, the review aims at presenting update-to-date details, so as to enhance awareness of potential therapeutics, and thus, to catalyze their appropriate use in combating the pandemic.

scholarly journals Testing the Mig-HealthCare Algorithm in Greece

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
E Riza ◽  
P Karnaki ◽  
D Zota ◽  
A Linos
Keyword(s):  
Health Care ◽  
Early Stage ◽  
Health Care Systems ◽  
Health Conditions ◽  
Health Issues ◽  
Host Countries ◽  
Local Hospital ◽  
Raising Awareness ◽  
Significant Burden ◽  
Care Systems

Abstract The Mig-HealthCare Algorithm is a tool, comprising a set of questions developed with the aim to (a) guide the user on how to access all the categories and tools that are available through the Roadmap & Toolbox (b) help the user identify the health issues of importance when providing care to a specific migrant/refugee. At the end of a series of questions, a brief report summarizing the main outcomes is generated. The algorithm was tested in Greece in two mainland reception centres and a local hospital in an area serving migrants/refugees. Results discuss the usefulness of the algorithm for improving the delivery of appropriate health services to migrants/refugees and its importance in raising awareness about the health conditions which are crucial for migrants/refugees and are expected to pose a significant burden on the health care systems of host countries unless dealt with adequately at an early stage.

scholarly journals Computer-Aided Pharmacoepidemiology in Drug Use and Safety: Examining the Intersection between Data Science and Medicines Research

2021 ◽  
Author(s):  
Ibrahim Chikowe ◽  
Elias Peter Mwakilama
Keyword(s):  
Health Care ◽  
Clinical Trials ◽  
Research Agenda ◽  
Data Science ◽  
Health Care Systems ◽  
Computer Aided ◽  
Care Systems ◽  
Research Narrative ◽  
Randomised Controlled ◽  
Improving Health Care

Pharmacoepidemiology is a relatively new area of study that focuses on research aimed at producing data about drugs’ usage and safety in well-defined populations. Its significant impact on patient safety has translated into improving health care systems worldwide, where it has been widely adopted. This field has developed to an extent that policy and guidelines makers have started using its evidence alongside that produced from randomised controlled clinical trials. Although this significant improvement has been partly attributed to the adoption of statistics and computer-aided models into the way pharmacoepidemiology studies are designed and conducted, certain gaps still exist. This chapter reports some of the significant developments made, along with the gaps observed so far, in the adoption of statistics and computing into pharmacoepidemiology research. The goal is to highlight efforts that have led to the new pharmacoepidemiology developments, while examining the intersection between data science and pharmacology through research narrative reviews of computer-aided pharmacology. The chapter shows the significant number of initiatives that have been applied/adopted to improve pharmacoepidemiology research. Nonetheless, further developments in integrating pharmacoepidemiology with computers and statistics are needed in order to enhance the research agenda.

Use of imaging for staging of early breast cancer in two integrated health care systems.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 184-184
Author(s):  
Erin Elizabeth Hahn ◽  
Tania Tang ◽  
Janet S. Lee ◽  
Corrine Munoz-Plaza ◽  
Joyce O Adesina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Cancer Patients ◽  
Early Stage ◽  
Health Care Systems ◽  
Integrated Health Care ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Chart Abstraction ◽  
Care Systems

184 Background: The initial ASCO “Top 5” list, created as part of the Choosing Wisely campaign, recommends against use of imaging for staging of early stage breast cancer in asymptomatic women at low risk for metastasis. The objective of this study was to measure and compare use of imaging for staging in two large integrated health care systems, Kaiser Permanente (KP) and Intermountain Healthcare (IH). We also sought to distinguish whether imaging was used for routine staging or for diagnostic purposes. Methods: We identified stage 0-IIB breast cancer patients diagnosed between January 1, 2010 and December 31, 2012 with first primary malignancy from tumor registries in three KP regions (Southern California, Northwest, and Mid-Atlantic) and IH. Using the KP and IH electronic health records, we identified use of imaging tests (PET, CT, bone scan) during the staging window (30 days prior to diagnosis up to initial surgery). We performed chart abstraction on a random sample of patients who received an imaging test to identify indication. Results: For the total sample of 10,014, mean age at diagnosis was 60 (range 22-99); with 21% stage 0, 47% stage I, 32% stage II. Overall, 8% of patients (792 patients) received at least one imaging test during the staging window, including 8% at KP and 6% at IH (p=0.0005). Chart abstraction (N=129) revealed that overall, almost half of all imaging tests (48%) were performed to evaluate a symptom, sign or prior imaging finding, including 55% at KP and 32% at IH. Conclusions: Use of imaging for staging of low-risk breast cancer was very low in both health care systems, with clinically trivial differences between them. Approximately half of imaging services were in response to a sign or symptom. Strategies to reduce use of imaging at staging for early stage breast cancer patients within these health care systems are unlikely to yield meaningful improvement. [Table: see text]

scholarly journals Use of Imaging for Staging of Early-Stage Breast Cancer in Two Integrated Health Care Systems: Adherence With a Choosing Wisely Recommendation

2015 ◽  
Vol 11 (3) ◽  
pp. e320-e328 ◽  
Author(s):  
Erin E. Hahn ◽  
Tania Tang ◽  
Janet S. Lee ◽  
Corrine Munoz-Plaza ◽  
Joyce O. Adesina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Early Stage ◽  
Health Care Systems ◽  
Integrated Health Care ◽  
Low Risk ◽  
Choosing Wisely ◽  
Early Stage Breast Cancer ◽  
Care Systems ◽  
Risk Breast Cancer

Use of imaging for staging of low-risk breast cancer was similar in both systems, and slightly lower than has been reported in the literature.

scholarly journals Neuromodulation for Pain: A Comprehensive Survey and Systematic Review of Clinical Trials and Connectomic Analysis of Brain Targets

2021 ◽  
pp. 1-12
Author(s):  
Kazuaki Yamamoto ◽  
Gavin J.B. Elias ◽  
Michelle E. Beyn ◽  
Ajmal Zemmar ◽  
Aaron Loh ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Pain Relief ◽  
Brain Stimulation ◽  
Health Care Systems ◽  
Network Connectivity ◽  
Mapping Analysis ◽  
Care Systems ◽  
Comprehensive Survey ◽  
Clinical Trials Registry

<b><i>Background:</i></b> Chronic pain is a debilitating condition that imposes a tremendous burden on health-care systems around the world. While frontline treatments for chronic pain involve pharmacological and psychological approaches, neuromodulation can be considered for treatment-resistant cases. Neuromodulatory approaches for pain are diverse in both modality and target and their mechanism of action is incompletely understood. <b><i>Objectives:</i></b> The objectives of this study were to (i) understand the current landscape of pain neuromodulation research through a comprehensive survey of past and current registered clinical trials (ii) investigate the network underpinnings of these neuromodulatory treatments by performing a connectomic mapping analysis of cortical and subcortical brain targets that have been stimulated for pain relief. <b><i>Methods:</i></b> A search for clinical trials involving pain neuromodulation was conducted using 2 major trial databases (ClinicalTrials.gov and the International Clinical Trials Registry Platform). Trials were categorized by variables and analyzed to gain an overview of the contemporary research landscape. Additionally, a connectomic mapping analysis was performed to investigate the network connectivity patterns of analgesic brain stimulation targets using a normative connectome based on a functional magnetic resonance imaging dataset. <b><i>Results:</i></b> In total, 487 relevant clinical trials were identified. Noninvasive cortical stimulation and spinal cord stimulation trials represented 49.3 and 43.7% of this count, respectively, while deep brain stimulation trials accounted for &#x3c;3%. The mapping analysis revealed that superficial target connectomics overlapped with deep target connectomics, suggesting a common pain network across the targets. <b><i>Conclusions:</i></b> Research for pain neuromodulation is a rapidly growing field. Our connectomic network analysis reinforced existing knowledge of the pain matrix, identifying both well-described hubs and more obscure structures. Further studies are needed to decode the circuits underlying pain relief and determine the most effective targets for neuromodulatory treatment.

scholarly journals Valorization of clinical trials from the Italian National Health Service perspective: definition and first application of a model to estimate avoided costs

2020 ◽  
Vol 7 (1) ◽  
pp. 26-32
Author(s):  
Americo Cicchetti ◽  
Domenico Addesso ◽  
Filippo Elvino Leone ◽  
Antonino Amato ◽  
Luca Angerame ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Health Care Systems ◽  
Economic Value ◽  
Public Health Care ◽  
Management Tool ◽  
Healthcare Organizations ◽  
Experimental Site ◽  
Italian National Health Service ◽  
Care Systems

Introduction: From the perspective of healthcare organizations and public health care systems, the value of a clinical trial can be assessed from a clinical and economical perspective. However, to date, there is no standardized model for systematically capturing the economic value of clinical trials at organizational and system levels. The aim of this study was to develop and test a methodology for estimating the avoided costs deriving from the management of patients as part of a clinical trial. Methods: Our methodology is based on the assumption that the economic value of a clinical trial derives from 1) the funding received by the experimental site from a trial’s sponsor, and from 2) the cost avoided by the experimental site with the treatment of patients within a study and not according to standard care by the experimental site.  Results: By applying the methodology to onco-hematological clinical trials conducted in two academic hospitals from 2011 to 2016, we demonstrate that savings between 2 million and 4 million euros were achieved over a five-year period. Thus, for every 1,000 euros invested by the pharmaceutical company into the clinical studies conducted at these hospitals, the hospitals saved on average 2,200 euros due to costs not incurred as a result of the trials. Conclusions: The study has proposed and tested a methodology for estimating the economic value of clinical trials by taking into account avoided costs deriving from the treatment of patients enrolled in sponsored trials. The study has proposed a management tool for healthcare institutions to govern clinical trials.

scholarly journals SURROGATE ENDPOINT: ALTERNATIVE FOR EARLY ASSESSMENT OF A POTENTIAL TREATMENT EFFECT

2019 ◽  
Vol 9 (4-s) ◽  
pp. 819-821
Author(s):  
Rada Santosh Kumar ◽  
Ganesh Sai Myneni
Keyword(s):  
Health Care ◽  
Clinical Trials ◽  
Clinical Benefit ◽  
Health Care Policy ◽  
Health Care Systems ◽  
Surrogate Endpoint ◽  
Surrogate Endpoints ◽  
Early Assessment ◽  
Health Technologies ◽  
Care Systems

The efficacy of health technologies, medicines and medical devices should be demonstrated in trails that evaluate final patient-relevant outcomes such as survival or morbidity. We provide a summary of the present use of surrogate end points in health care policy, discussing the case for and against their reviewing and adoption validation methods. Although the use of surrogates can be problematic, they can be validated and selected properly, offers important chances for more efficient clinical trials and faster access to new health technologies that benefit health care systems and patients. In early drug development studies, tumor response is often the true primary endpoint. Usually clinical trials are needed to show that it can be dependent upon to predict, or correlate with, clinical benefit in a context of use. Surrogate endpoints that have undergone this ample testing are called validated surrogate endpoints and these are accepted by the Food and Drug Administration as evidence of benefit. Choosing the right surrogate endpoint and proving that it can predict the intended clinical benefit, however, is not always straightforward. When a disease has been sufficiently studied, surrogate endpoints can measure the underlying cause of a disease (such as low thyroxine levels and hypothyroidism) or an effect that predicts the ultimate outcome (such as measuring diuresis, which is expected to improve symptoms of heart failure). 

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