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1.
Journal of the American Academy of Child and Adolescent Psychiatry ; 61(10 Supplement):S294, 2022.
Article in English | EMBASE | ID: covidwho-2076268

ABSTRACT

Objectives: The objectives are to describe the history and science behind extrapolation of pediatric efficacy, and to provide examples of the successful and unsuccessful application of extrapolation of efficacy in different therapeutic areas outside of psychiatry. Method(s): A review will be conducted of FDA, European, and international regulatory documents and articles from the medical literature discussing extrapolation of pediatric efficacy. Examples of medications with pediatric labeling that is based on extrapolation of pediatric efficacy will be identified with the help of the FDA pediatric labeling database. Result(s): The concept of extrapolation of pediatric efficacy was first introduced with the pediatric rule in 1994. Whether or not extrapolation of pediatric efficacy is appropriate depends on our understanding of a disease's clinical characteristics, developmental time course, prognosis, and pathophysiology, as well as the developmental pharmacokinetics and pharmacology of the drug or biologic. Examples from several therapeutic areas outside of psychiatry will be discussed, including monoclonal antibodies and vaccines against SARS-CoV-2. Conclusion(s): Extrapolation of pediatric efficacy is an important tool in pediatric drug development. Not only does it potentially reduce the number of pediatric patients who must be subjected to clinical trials, and potentially to placebo, but it also is one of the fastest approaches to providing pediatric data to inform clinicians. PPC, R, SZ Copyright © 2022

2.
The Sport Journal ; 25(10), 2022.
Article in English | CAB Abstracts | ID: covidwho-1957922

ABSTRACT

Purpose: As a result of the COVID-19 pandemic, national restrictions were implemented limiting social gatherings and disrupting many facets of everyday life including sports. To gain a better understanding of how the COVID-19 pandemic has affected the social and emotional well-being of children and adolescents in sports, the present study examined parental perspectives of female youth competitive cheerleaders during the national pandemic.

3.
Microscopy and Microanalysis ; 28(S1):3220-3222, 2022.
Article in English | ProQuest Central | ID: covidwho-1947162
4.
PLoS Pathog ; 18(4): e1009925, 2022 04.
Article in English | MEDLINE | ID: covidwho-1808578

ABSTRACT

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable but low levels of antiviral antibodies after infusion. In comparison to the control animals, CCP-treated animals had similar levels of viral RNA in upper and lower respiratory tract secretions, similar detection of viral RNA in lung tissues by in situ hybridization, but lower amounts of infectious virus in the lungs. CCP-treated animals had a moderate, but statistically significant reduction in interstitial pneumonia, as measured by comprehensive lung histology. Thus overall, therapeutic benefits of CCP were marginal and inferior to results obtained earlier with monoclonal antibodies in this animal model. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antiviral Agents , COVID-19/therapy , Humans , Immunization, Passive , Macaca mulatta , RNA, Viral
5.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333856

ABSTRACT

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT 50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable levels of antiviral antibodies after infusion. In comparison to the control animals, they had similar levels of virus replication in the upper and lower respiratory tract, but had significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses. AUTHOR SUMMARY: The results of treating SARS-CoV-2 infected hospitalized patients with COVID-19 convalescent plasma (CCP), collected from survivors of natural infection, have been disappointing. The available data from various studies indicate at best moderate clinical benefits only when CCP with high titer of neutralizing antibodies was infused early in infection. The macaque model of SARS-CoV-2 infection can be useful to gain further insights in the value of CCP therapy. In this study, animals were infected with SARS-CoV-2 and the next day, were infused with pooled human convalescent plasma, selected to have a very high titer of neutralizing antibodies. While administration of CCP did not result in a detectable reduction in virus replication in the respiratory tract, it significantly reduced lung inflammation. These data, combined with the results of monoclonal antibody studies, emphasize the need to use products with high titers of neutralizing antibodies, and guide the future development of CCP-based therapies.

6.
Arthritis & Rheumatology ; 73:4157-4158, 2021.
Article in English | Web of Science | ID: covidwho-1727997
7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312350

ABSTRACT

Objectives: The second wave of the coronavirus pandemic is now established, occurring at a time of winter pressure on acute care in the NHS. This is likely to be more challenging then the first wave for the diagnosis of COVID-19 because of the similar symptomology with other respiratory conditions highly prevalent in winter. This study sought to understand the care pathways in place in UK NHS hospitals during the first wave (March-July 2020) for identification of patients with COVID-19 and to learn lessons to inform optimal testing strategies within the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR). Design: , setting & participants Sixteen hospital-based clinicians from 12 UK NHS Trusts covering 10 different specialties were interviewed following a semi-structured topic guide. Data were coded soon after the interviews and analysed thematically. Results: We developed a diagrammatic, high-level visualisation of the care pathway describing the main clinical decisions associated with the diagnosis and management of patients with suspected COVID-19. COVID-19 testing influenced infection control considerations more so than treatment decisions. Two main features of service provision influenced the patient management significantly: access to rapid laboratory testing and the number of single occupancy rooms. If time to return of result was greater than 24 hours, patients with a presumptive diagnosis would often be cohorted based on clinical suspicion alone. Undetected COVID-19 during this time could therefore lead to an increased risk of viral transmission. Conclusions: During the winter months, priority for provision of rapid testing at admission should be given to hospitals with limited access to laboratory services and single room availability. Access to rapid testing is essential for urgent decisions related to emergency surgery, maternity services and organ transplant. The pathway and prioritization of need will inform the economic modelling, clinical evaluations, and implementation of new clinical tests in UK.

8.
Implement Sci Commun ; 2(1): 139, 2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1581964

ABSTRACT

BACKGROUND: The purpose of this study is to develop a theory-driven understanding of the barriers and facilitators underpinning physicians' attitudes and capabilities to implementing SARS-CoV-2 point-of-care (POC) testing into primary care practices. METHODS: We used a secondary qualitative analysis approach to re-analyse data from a qualitative, interview study of 22 primary care physicians from 21 primary care practices across three regions in England. We followed the three-step method based on the Behaviour Change Wheel to identify the barriers to implementing SARS-CoV-2 POC testing and identified strategies to address these challenges. RESULTS: Several factors underpinned primary care physicians' attitudes and capabilities to implement SARS-CoV-2 POC testing into practice. First, limited knowledge of the SARS-CoV-2 POC testing landscape and a demanding workload affected physicians' willingness to use the tests. Second, there was scepticism about the insufficient evidence pertaining to the clinical efficacy and utility of POC tests, which affected physicians' confidence in the accuracy of tests. Third, physicians would adopt POC tests if they were prescribed and recommended by authorities. Fourth, physicians required professional education and training to increase their confidence in using POC tests but also suggested that healthcare assistants should administer the tests. Fifth, physicians expressed concerns about their limited workload capacity and that extra resources are needed to accommodate any anticipated changes. Sixth, information sharing across practices shaped perceptions of POC tests and the quality of information influenced physician perceptions. Seventh, financial incentives could motivate physicians and were also needed to cover the associated costs of testing. Eighth, physicians were worried that society will view primary care as an alternative to community testing centres, which would change perceptions around their professional identity. Ninth, physicians' perception of assurance/risk influenced their willingness to use POC testing if it could help identify infectious individuals, but they were also concerned about the risk of occupational exposure and potentially losing staff members who would need to self-isolate. CONCLUSIONS: Improving primary care physicians' knowledgebase of SARS-CoV-2 POC tests, introducing policies to embed testing into practice, and providing resources to meet the anticipated demands of testing are critical to implementing testing into practice.

9.
British Journal of Surgery ; 108(SUPPL 6):vi286, 2021.
Article in English | EMBASE | ID: covidwho-1569666

ABSTRACT

Introduction: COVID-19 resulted in Regional tiered restrictions being introduced across the UK with subsequent implications for planned and emergency care. Specific to Merseyside Tier 4 and Tier 2 restrictions were introduced in late 2020. At the onset of the pandemic in the Spring, elective work ceased, and emergency admissions were minimal. The purpose of this study was to examine the volume and nature of all emergency admissions to a Urology unit in Merseyside in the 2nd wave of the pandemic during two different tiers of national restrictions. Method: A prospective audit examining all emergency urological activity was conducted in Whiston Hospital from October 2020 when the Tier 4 restrictions were introduced to Tier 2 was introduced. Data was obtained by identifying patients using the electronic theatre listing system. Results: A total of 52 emergency cases were performed (24 in November Tier 4, 28 in December Tier 2). A total of 12 different procedures were performed. The commonest procedure performed was stent insertion (26), followed by scrotal exploration (7). One patient required transfer to a different hospital. In total 4 calls were made by general surgery and 2 by gynaecology for urological assistance in theatre. Two urology patients returned to theatre. Direct Consultant involvement occurred in 19 cases (37%). Conclusions: Unlike the Spring lockdown acute urology operations presented despite regional restrictions. A total of 52 cases were performed with more occurring in Tier 2. Stent insertion was the commonest procedure with the majority of the cases performed by registrars.

11.
Journal of Patient Safety and Risk Management ; : 25160435211054207, 2021.
Article in English | Sage | ID: covidwho-1523271

ABSTRACT

IntroductionSuccessful adoption of POCTs (Point-of-Care tests) for COVID-19 in care homes requires the identification of ideal use cases and a full understanding of the contextual and usability factors that affect test results and minimise biosafety risks. This paper presents a scoping-usability and test performance study of a microfluidic immunofluorescence assay for COVID-19 in care homes.MethodsA mixed-methods evaluation was conducted in four UK care homes to scope usability and to assess the agreement with qRT-PCR. A dry run with luminescent dye was conducted to explore biosafety issues.ResultsThe agreement analysis was conducted on 227 asymptomatic participants (159 staff and 68 residents) and 14 symptomatic participants (5 staff and 9 residents). Asymptomatic specimens showed 50% (95% CI:1.3%?98.7%) positive agreement and 96% (95% CI: 92.5%?98.1%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.911 (95% CI: 0.857?0.965). Symptomatic specimens showed 83.3% (95% CI: 35.9%?99.6%) positive agreement and 100% (95% CI: 63.1%?100%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.857 (95% CI: 0.549?1). The dry run highlighted four main sources of contamination that led to the modification of the standard operating procedures. Simulation post-modification showed no further evidence of contamination.ConclusionCareful consideration of biosafety issues and contextual factors associated with care home are mandatory for safe use the POCT. Whilst POCT may have some utility for ruling out COVID-19, further diagnostic accuracy evaluations are needed to promote effective adoption.

12.
HRB Open Res ; 4:95, 2021.
Article in English | PubMed | ID: covidwho-1464041

ABSTRACT

Background:  The COVID-19 pandemic and associated lockdowns have had a dramatic impact on many people, but individuals with an intellectual disability, given the prevalence of congregate living and high levels of co-morbid conditions, may be particularly vulnerable at this time. A prior initial survey of participants of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) found that, despite a majority of participants being tested, only a small proportion had tested positive for COVID-19. Furthermore, despite some reporting positive aspects to the lockdown, a similar proportion were experiencing stress or anxiety during the pandemic. The pandemic and lockdowns have continued, and it is possible that experiences and consequences have changed over time. Aim: To explore over time and in greater depth the impact of COVID-19 and associated lockdowns and to further establish rates of infection, rates of vaccination and participants' experiences. Methods: A structured questionnaire for people with intellectual disability participating in the IDS-TILDA longitudinal study, to be administered by telephone/video in summer 2021. Where participants are unable to respond independently, a proxy respondent will be invited to either assist the participant or answer questions on their behalf. This questionnaire will include questions from the first COVID-19 questionnaire, with extra questions assessing "long COVID" (i.e. COVID-19 lasting for 12 weeks or longer), infection control behaviours, changes in mental health, social contacts and loneliness, frailty, healthcare, and incidence of vaccination. Impact: The results of this survey will be used to inform healthcare provision for people with intellectual disability during the latter stages of the lockdown and into the future.

13.
Annals of Emergency Medicine ; 78(2):S4-S5, 2021.
Article in English | EMBASE | ID: covidwho-1351448

ABSTRACT

Study Objectives: Interpersonal relationships between emergency medicine resident physicians and their colleagues is key for resident wellness and for optimizing patient care. Studies have shown that the COVID-19 pandemic has reduced social connectedness and negatively impacted workplace social capital in many non-medical professions, yet studies are limited in the medical field, particularly with physicians. This project sought to uncover resident physician perspectives on the impact of COVID-19 on professional relationships and to gain ideas on how to optimize workplace social capital despite and beyond the current limitations of the pandemic. Methods: This study was conducted at a single academic hospital in the United States between March-April 2021. Data was collected from emergency medicine residents via open-ended response online surveys and a semi-structured focus group discussion. A team of three investigators independently analyzed data from open-ended survey responses and the focus group transcription, using a grounded-theory approach and consensus of the independent analyses was subsequently generated to identify final themes and subthemes. Results: Three main themes regarding resident perspective on professional interpersonal relationships and social capital were identified: team, trust, and support. We also report the 6 core factors discussed by residents that have changed secondary to the COVID-19 pandemic. EM resident physicians feel that the COVID-19 pandemic has impacted environment, socialization, staff turnover, teaching/debriefing, capacity limits and approach to education, which have demonstrated an overall negative impact on interpersonal relationships and social capital. It has also, however, positively impacted a sense of unity within the emergency department team that residents feel has enhanced relationships and social capital. Conclusions: The COVID-19 pandemic will have lasting impacts on the way our hospitals and residencies function. The findings of this study may help to ignite discussion on how we can build on the positive, while limit the negative impacting features that have been shaped from the COVID-19 pandemic. [Formula presented] [Formula presented] [Formula presented]

14.
JAMA Intern Med ; 181(10): 1322-1323, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1347378

Subject(s)
COVID-19 , Humans , SARS-CoV-2
15.
MAI Journal ; 10(1):41-45, 2021.
Article in English | Scopus | ID: covidwho-1342070

ABSTRACT

The effects of the COVID-19 lockdown and physical distancing were broad, impacting multiple sectors, particularly health, for Mäori and Indigenous peoples. This article considers health and well-being using Te Whare Tapa Whä, and looks at the experiences and voices of kuia and koroheke—considered to be at high risk of contracting coronavirus—to better understand their health and well-being impacts from physical distancing. This article then reflects on these experiences to identify how help groups can best support communities in future lockdown situations. The recommendations for future support efforts are threefold and centre on increasing coordination amongst the efforts of the different help groups, using a holistic approach such as Te Whare Tapa Whä to address the various pillars of health, and considering individual health and well-being needs. © 2021, Nga Pae o te Maramatanga. All rights reserved.

16.
Birth Defects Res ; 113(17): 1245-1256, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1321678

ABSTRACT

BACKGROUND: Hydroxychloroquine is a treatment for rheumatic disease and considered safe during pregnancy. Interest in hydroxychloroquine has increased as it is being examined as a potential treatment and prophylaxis for coronavirus disease 2019. Data on the risks of specific birth defects associated with hydroxychloroquine use are sparse. METHODS: Using data from two case-control studies (National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study), we described women who reported hydroxychloroquine use in pregnancy and the presence of specific major birth defects in their offspring. Cases had at least one major birth defect and controls were live-born healthy infants. Women self-reported medication use information in the few months before pregnancy through delivery. RESULTS: In total, 0.06% (19/31,468) of case and 0.04% (5/11,614) of control mothers in National Birth Defects Prevention Study, and 0.04% (11/29,838) of case and 0.05% (7/12,868) of control mothers in Birth Defects Study reported hydroxychloroquine use. Hydroxychloroquine users had complicated medical histories and frequent medication use for a variety of conditions. The observed birth defects among women taking hydroxychloroquine were varied and included nine oral cleft cases; the elevated observed:expected ratios for specific oral cleft phenotypes and for oral clefts overall had 95% confidence intervals that included 1.0. CONCLUSION: While teratogens typically produce a specific pattern of birth defects, the observed birth defects among the hydroxychloroquine-exposed women did not present a clear pattern, suggesting no meaningful evidence for the risk of specific birth defects. The number of exposed cases is small; results should be interpreted cautiously.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/drug therapy , Female , Humans , Hydroxychloroquine/adverse effects , Maternal Exposure/adverse effects , Pregnancy , SARS-CoV-2
17.
Journal of Applied Research in Intellectual Disabilities ; 34(5):1311-1312, 2021.
Article in English | Web of Science | ID: covidwho-1306140
18.
PLoS Pathog ; 17(7): e1009688, 2021 07.
Article in English | MEDLINE | ID: covidwho-1298083

ABSTRACT

There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , Lung/pathology , SARS-CoV-2/immunology , Virus Replication , Animals , Antibodies, Monoclonal/blood , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/pathology , COVID-19/virology , Disease Models, Animal , Female , Lung/diagnostic imaging , Macaca mulatta , Male , Multivariate Analysis , Radiography , Respiratory System/virology , SARS-CoV-2/physiology , Time Factors , Treatment Outcome , Virus Replication/immunology
19.
BMC Health Serv Res ; 21(1): 532, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1249555

ABSTRACT

OBJECTIVES: The second wave of the coronavirus pandemic is now established, occurring at a time of winter pressure on acute care in the NHS. This is likely to be more challenging then the first wave for the diagnosis of COVID-19 because of the similar symptomology with other respiratory conditions highly prevalent in winter. This study sought to understand the care pathways in place in UK NHS hospitals during the first wave (March-July 2020) for identification of patients with COVID-19 and to learn lessons to inform optimal testing strategies within the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR). DESIGN, SETTING & PARTICIPANTS: Sixteen hospital-based clinicians from 12 UK NHS Trusts covering 10 different specialties were interviewed following a semi-structured topic guide. Data were coded soon after the interviews and analysed thematically. RESULTS: We developed a diagrammatic, high-level visualisation of the care pathway describing the main clinical decisions associated with the diagnosis and management of patients with suspected COVID-19. COVID-19 testing influenced infection control considerations more so than treatment decisions. Two main features of service provision influenced the patient management significantly: access to rapid laboratory testing and the number of single occupancy rooms. If time to return of result was greater than 24 h, patients with a presumptive diagnosis would often be cohorted based on clinical suspicion alone. Undetected COVID-19 during this time could therefore lead to an increased risk of viral transmission. CONCLUSIONS: During the winter months, priority for provision of rapid testing at admission should be given to hospitals with limited access to laboratory services and single room availability. Access to rapid testing is essential for urgent decisions related to emergency surgery, maternity services and organ transplant. The pathway and prioritization of need will inform the economic modelling, clinical evaluations, and implementation of new clinical tests in UK.


Subject(s)
COVID-19 Testing , COVID-19 , Female , Hospitals , Humans , Pregnancy , SARS-CoV-2 , United Kingdom/epidemiology
20.
Age Ageing ; 50(5): 1442-1444, 2021 09 11.
Article in English | MEDLINE | ID: covidwho-1226520

ABSTRACT

COVID-19 has devastated care homes. Point-of-care tests (POCTs), mainly using lateral flow devices (LFDs), have been deployed hurriedly without much consideration of their usability or impact on care workflow. Even after the pandemic, POCTs, particularly multiplex tests, may be an important control against spread of SARS-CoV-2 and other respiratory infections in care homes by enabling identification of cases. They should not, however, replace other infection control measures such as barrier methods and quarantine. Adherence to LFDs as implemented among care home staff is suboptimal. Other tests-such as point-of-care polymerase chain reaction and automated antigen tests-would also need to be accommodated into care home workflows to improve adherence. The up-front costs of POCTs are straightforward but additional costs, including staffing preparation and reporting processes and the impacts of false positive and negative tests on absence rates and infection days, are more complex and as yet unquantified. A detailed appraisal is needed as the future of testing in care homes is considered.


Subject(s)
COVID-19 , Humans , Pandemics , Point-of-Care Testing , Policy , SARS-CoV-2
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