scholarly journals Proposed multidimensional pain outcome methodology to demonstrate analgesic drug efficacy and facilitate future drug approval for piglet castration

2021 ◽  
pp. 1-14
Author(s):  
Angela Baysinger ◽  
Sherrie R. Webb ◽  
Jennifer Brown ◽  
Johann F. Coetzee ◽  
Sara Crawford ◽  
...  
Keyword(s):  
Drug Efficacy ◽  
Drug Approval ◽  
The United States ◽  
Indirect Measurement ◽  
Mitigation Strategies ◽  
Analgesic Drug ◽  
Biological Responses ◽  
Gait Parameters ◽  
Pain Outcome ◽  
Future Drug

Abstract Castration of male piglets in the United States is conducted without analgesics because no Food and Drug Administration (FDA) approved products are labeled for pain control in swine. The absence of approved products is primarily due to a wide variation in how pain is measured in suckling piglets and the lack of validated pain-specific outcomes individually indistinct from other biological responses, such as general stress or inflammation responses with cortisol. Simply put, to measure pain mitigation, measurement of pain must be specific, quantifiable, and defined. Therefore, given the need for mitigating castration pain, a consortium of researchers, veterinarians, industry, and regulatory agencies was formed to identify potential animal-based outcomes and develop a methodology, based on the known scientific research, to measure pain and the efficacy of mitigation strategies. The outcome-based measures included physiological, neuroendocrine, behavioral, and production parameters. Ultimately, this consortium aims to provide a validated multimodal methodology to demonstrate analgesic drug efficacy for piglet castration. Measurable outcomes were selected based on published studies suggesting their validity, reliability, and sensitivity for the direct or indirect measurement of pain associated with surgical castration in piglets. Outcomes to be considered are observation of pain behaviors (i.e. ethogram defined behaviors and piglet grimace scale), gait parameters measured with a pressure mat, infrared thermography of skin temperature of the cranium and periphery of the eye, and blood biomarkers. Other measures include body weight and mortality rate. This standardized measurement of the outcome variable's primary goal is to facilitate consistency and rigor by developing a research methodology utilizing endpoints that are well-defined and reliably measure pain in piglets. The resulting methodology will facilitate and guide the evaluation of the effectiveness of comprehensive analgesic interventions for 3- to 5-day-old piglets following surgical castration.

New Drugs of 2012: A Concise Overview of the NMEs and Trends for Innovative Brand Market in the United States

2013 ◽  
Vol 6 (2) ◽  
pp. 2009-2013
Author(s):  
D Samba Reddy
Keyword(s):  
Drug Approval ◽  
The United States ◽  
New Drugs ◽  
New Combination ◽  
Drug Status ◽  
Combination Drug ◽  
Human Cord Blood ◽  
Life Saving ◽  
Genomics And Proteomics ◽  
The Face

Thirty-nine (39) new drugs have been approved by the U.S. FDA in 2012, a record highest number of approvals since 1996. The record is a sign that pharma companies are poised to tap recent advances from genomics and proteomics. This list includes novel new drugs, known as new molecular entities (NMEs), biologics and new products. Many life-saving drugs are approved for marketing. The list includes a total of 10 drugs for cancer treatment, and nearly a quarter of those approved in 2012 had orphan drug status.  Among the breakthrough drugs approved in 2012 were ivacaftor (cystic fibrosis), vasmodegib (skin cancer), HPC-C (human cord blood product), ruxolitinib (myelofibrosis) and a new combination drug to treat HIV. In addition,  several unique products were approved for the treatment of macular degeneration, chronic weight management, overactive bladder, actinic keratosis, erectile dysfunction, glaucoma, respiratory distress syndrome, and COPD. The approval of 39 drugs in 2012 underscores a robust success rate and confirms that innovation is once again beginning to pay off. In the existing climate of reduced revenues in the face of generic competitions, the future and survival of big companies rests heavily on their unique niche products. It is apparent that big Pharma and a growing number of emerging Biotechs alike have focused their attention on developing new NMEs for rare diseases. In 2012, the length of the FDA’s review is shorter than agencies in other countries. Innovative models adopted for R&D strategies, communications, and new regulatory changes appear to shorten development timelines. Despite record drug approvals, there is bleak scope for blockbusters because most of these drugs have a limited market. The pipeline for blockbusters appears very low. However, there is unmet medical need for new drugs in autism, Alzheimer’s disease and epilepsy. Overall, the new drug approval list unveils unique and reemerging trends indicating that the pharma companies are poised for big growth from new brands approved for marketing for narrow-spectrum indications.    

scholarly journals 307 A systems approach to understanding biosecurity decision-making

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 43-43
Author(s):  
Scott C Merrill ◽  
Christopher Koliba ◽  
Gabriela Bucini ◽  
Eric Clark ◽  
Luke Trinity ◽  
...  
Keyword(s):  
Decision Making ◽  
Negative Impact ◽  
Risk Mitigation ◽  
African Swine Fever Virus ◽  
The United States ◽  
Mitigation Strategies ◽  
Communication Strategy ◽  
Livestock Industry ◽  
Diarrhea Virus ◽  
Operational Level

Abstract Disease and its consequences result in social and economic impacts to the US animal livestock industry, ranging from losses in human capital to economic costs in excess of a billion dollars annually. Impacts would dramatically escalate if a devastating disease like Foot and Mouth Disease or African Swine Fever virus were to emerge in the United States. Investing in preventative biosecurity can reduce the likelihood of disease incursions and their negative impact on our livestock industry, yet uncertainty persists with regards to developing an effective biosecurity structure and culture. Here we show the implications of human behavior and decision making for biosecurity effectiveness, from the operational level to the owner/managerial level and finally to the systems level. For example, adjustments to risk messaging strategies could double worker compliance with biosecurity practices at the operational level. The improvement of our risk communication strategy may increase willingness to invest in biosecurity. Furthermore, the adaptation of policies could nudge behavior so that we observe a short disease outbreak followed by a quick eradication instead of a pandemic. Our research shows how the emergence of now-endemic diseases, such as Porcine Epidemic Diarrhea virus, cannot be adequately modeled without the use of a human behavioral component. Focusing solely on any one sector or level of the livestock system is not sufficient to predict emergent disease patterns and their social and economic impact on livestock industries. These results provide insight toward developing more effective risk mitigation strategies and ways to nudge behavior toward more disease resilient systems.

scholarly journals COVID-TRACK: world and USA SARS-COV-2 testing and COVID-19 tracking

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ye Emma Zohner ◽  
Jeffrey S. Morris
Keyword(s):  
Web Application ◽  
The United States ◽  
Mitigation Strategies ◽  
Time Lags ◽  
Policy Makers ◽  
Major Health ◽  
Dynamic Representation ◽  
Graphical Displays ◽  
The Usa ◽  
User Friendly

Abstract Background The COVID-19 pandemic has caused major health and socio-economic disruptions worldwide. Accurate investigation of emerging data is crucial to inform policy makers as they construct viral mitigation strategies. Complications such as variable testing rates and time lags in counting cases, hospitalizations and deaths make it challenging to accurately track and identify true infectious surges from available data, and requires a multi-modal approach that simultaneously considers testing, incidence, hospitalizations, and deaths. Although many websites and applications report a subset of these data, none of them provide graphical displays capable of comparing different states or countries on all these measures as well as various useful quantities derived from them. Here we introduce a freely available dynamic representation tool, COVID-TRACK, that allows the user to simultaneously assess time trends in these measures and compare various states or countries, equipping them with a tool to investigate the potential effects of the different mitigation strategies and timelines used by various jurisdictions. Findings COVID-TRACK is a Python based web-application that provides a platform for tracking testing, incidence, hospitalizations, and deaths related to COVID-19 along with various derived quantities. Our application makes the comparison across states in the USA and countries in the world easy to explore, with useful transformation options including per capita, log scale, and/or moving averages. We illustrate its use by assessing various viral trends in the USA and Europe. Conclusion The COVID-TRACK web-application is a user-friendly analytical tool to compare data and trends related to the COVID-19 pandemic across areas in the United States and worldwide. Our tracking tool provides a unique platform where trends can be monitored across geographical areas in the coming months to watch how the pandemic waxes and wanes over time at different locations around the USA and the globe.

Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18501-e18501
Author(s):  
Ryan Huu-Tuan Nguyen ◽  
Yomaira Silva ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Clinical Trials ◽  
Drug Approval ◽  
The United States ◽  
Cancer Clinical Trials ◽  
Cancer Prevalence ◽  
Fda Approval ◽  
The Us ◽  
Enrollment Data

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P< 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P< 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P< 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P< 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

Management of personal protective equipment during the COVID-19 pandemic in England and the state of New York: A comparative case study

2020 ◽  
Vol 18 (7) ◽  
pp. 71-89
Author(s):  
Amy Barber, BSc ◽  
Annaëlle Vinzent, BS ◽  
Imani Williams, BA
Keyword(s):  
New York ◽  
Supply Chain ◽  
Health Systems ◽  
Personal Protective Equipment ◽  
New York State ◽  
The United States ◽  
Mitigation Strategies ◽  
Comparative Case Study ◽  
Protective Equipment

Background: The COVID-19 crisis placed extraordinary demands on the supply of personal protective equipment (PPE) at the beginning of 2020. These were coupled with shocks to the supply chain resulting from the disease. Many typically well-resourced health systems faced subsequent shortages of equipment and had to implement new strategies to manage their stocks. Stockpiles of protective equipment were held in both the United States and United Kingdom intended to prevent shortages. Method: Cross-comparative case study approach by applying Pettigrew and Whipp’s framework for change management. Setting: The health systems of England and New York state from January 2020 to the end of April 2020. Results: Both cases reacted slowly to their outbreaks and faced problems with supplying enough PPE to their health systems. Their stockpiles were not enough to prevent shortages, with many distribution problems resulting from inadequate governance mechanisms. No sustainable responses to supply disruptions were implemented during the study period in either case. Health systems planned interventions along each part of the supply chain from production and importing, to usage guidelines. Conclusion: Global supply chains are vulnerable to disruptions caused by international crises, and existing mitigation strategies have not been wholly successful. The existence of stockpiles is insufficient to preventing shortages of necessary equipment in clinical settings. Both the governance and quality of stockpiles, as well as distribution channels are important for preventing shortages. At the time of writing, it is not possible to judge the strength of strategies adopted in these cases.

Sensitivity Analyses for a PWR SCC Case Using the Probabilistic Loss-of-Coolant-Accident (Pro-LOCA) Software

2016 ◽  
Author(s):  
Bruce A. Young ◽  
Sang-Min Lee ◽  
Paul M. Scott
Keyword(s):  
Nuclear Power ◽  
Power Plants ◽  
The United States ◽  
Design Criterion ◽  
Mitigation Strategies ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Piping System ◽  
Loss Of Coolant Accident ◽  
Piping Systems

As a means of demonstrating compliance with the United States Code of Federal Regulations 10CFR50 Appendix A, General Design Criterion 4 (GDC-4) requirement that primary piping systems for nuclear power plants exhibit an extremely low probability of rupture, probabilistic fracture mechanics (PFM) software has become increasingly popular. One of these PFM codes for nuclear piping is Pro-LOCA which has been under development over the last decade. Currently, Pro-LOCA is being enhanced under an international cooperative program entitled PARTRIDGE-II (Probabilistic Analysis as a Regulatory Tool for Risk-Informed Decision GuidancE - Phase II). This paper focuses on the use of a pre-defined set of base-case inputs along with prescribed variation in some of those inputs to determine a comparative set of sensitivity analyses results. The benchmarking case was a circumferential Primary Water Stress Corrosion Crack (PWSCC) in a typical PWR primary piping system. The effects of normal operating loads, temperature, leak detection, inspection frequency and quality, and mitigation strategies on the rupture probability were studied. The results of this study will be compared to the results of other PFM codes using the same base-case and variations in inputs. This study was conducted using Pro-LOCA version 4.1.9.

scholarly journals Estimating SARS-CoV-2 infections from deaths, confirmed cases, tests, and random surveys

2021 ◽  
Vol 118 (31) ◽  
pp. e2103272118
Author(s):  
Nicholas J. Irons ◽  
Adrian E. Raftery
Keyword(s):  
Herd Immunity ◽  
The United States ◽  
Sir Model ◽  
Mitigation Strategies ◽  
Time Varying ◽  
Fatality Rate ◽  
Multiple Sources ◽  
Population Prevalence ◽  
Sample Testing ◽  
True Infection

There are multiple sources of data giving information about the number of SARS-CoV-2 infections in the population, but all have major drawbacks, including biases and delayed reporting. For example, the number of confirmed cases largely underestimates the number of infections, and deaths lag infections substantially, while test positivity rates tend to greatly overestimate prevalence. Representative random prevalence surveys, the only putatively unbiased source, are sparse in time and space, and the results can come with big delays. Reliable estimates of population prevalence are necessary for understanding the spread of the virus and the effectiveness of mitigation strategies. We develop a simple Bayesian framework to estimate viral prevalence by combining several of the main available data sources. It is based on a discrete-time Susceptible–Infected–Removed (SIR) model with time-varying reproductive parameter. Our model includes likelihood components that incorporate data on deaths due to the virus, confirmed cases, and the number of tests administered on each day. We anchor our inference with data from random-sample testing surveys in Indiana and Ohio. We use the results from these two states to calibrate the model on positive test counts and proceed to estimate the infection fatality rate and the number of new infections on each day in each state in the United States. We estimate the extent to which reported COVID cases have underestimated true infection counts, which was large, especially in the first months of the pandemic. We explore the implications of our results for progress toward herd immunity.

scholarly journals COVID -19 in Geriatric Population

2021 ◽  
pp. 499-504
Author(s):  
Pratiksha S. Thakare ◽  
Samruddhi Gujar ◽  
Shakib Sheikh ◽  
Vrushali Dighikar
Keyword(s):  
Immune System ◽  
Case Fatality ◽  
Clinical Pathology ◽  
The United States ◽  
Severe Form ◽  
Mitigation Strategies ◽  
Geriatric Population ◽  
Control And Prevention ◽  
Coronavirus Infection ◽  
Prevention Center

The causative factors of Coronavirus disease mainly the viruses. Through news we aware that pneumonia cases seen recently in Wuhan city, China. Due to unknown causes. Coronaviruses that cause illness such as a common cold. The Coronavirus infection identified with respiratory symptoms and pneumonia, the severe form of coronavirus infection mainly associated with death and low immune system patients. It is very important for us to more focus on geriatric people because in our countries, geriatric group people facing health problems at this present situation. According to articles Clinical Pathology, Pathogenesis, Immunopathology, and Mitigation Strategies, in that said geriatric people and low immune system patient with symptoms related history are more prone to COVID infection. But according to recent information by WHO all people are at risk of coronavirus but mostly geriatric people facing more risk of developing a severe respiratory infection. Geriatric people easily get coronavirus syndrome due to physical changes that occur as increasing age. There were 95% of these deaths seen in geriatric people above 60 years older. Above 50% of all fatal conditions occurred in geriatric people between 60- 80 years ago. There having disease control and prevention center, which indicate that rates of hospitalizations, intensive care unit admissions and mortality reported among COVID-19 cases in the United States are substantially higher among patients older than 45 years compared with younger patients, with case-fatality rates exceeding 1.4% among patients aged 55 to 64 years and exceeding 2.7% among those aged 65 to 74 years.

METHADONE AND CHILDREN

PEDIATRICS ◽  
1971 ◽  
Vol 48 (2) ◽  
pp. 173-175
Author(s):  
Saul Blatman
Keyword(s):  
United States ◽  
Urban Areas ◽  
Methadone Maintenance ◽  
The United States ◽  
Heroin Addiction ◽  
Analgesic Drug ◽  
Heroin Addicts ◽  
Near Future

The increasing use of methadone maintenance (substitution) programs1-3 in the treatment of adult heroin addiction has created situations for children which require the attention of pediatricians. Methadone is an analgesic drug. In urban areas, thousands of heroin addicts are now receiving high dosage of methadone, usually 80 to 120 mg daily. This approach to heroin addiction has met with greater success than any other form of treatment. It is expected that increasing numbers of heroin addicts will be treated in the near future by this method throughout the United States and Canada.4 Pediatricians should focus on three aspects of the problem as follows:

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