Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

Disparities in self-reported healthcare access for airways disease in British Columbia, Canada, during the COVID-19 pandemic. Insights from a survey co-developed with people living with asthma and chronic obstructive pulmonary disease.

Patients' perspectives on the impact of the COVID-19 pandemic on their access to asthma and COPD healthcare could inform better, more equitable care delivery. We demonstrate this topic using British Columbia (BC), Canada, where the impact of the pandemic has not been described. We co-designed a cross-sectional survey with patient partners and administered it to a convenience sample of people living with asthma and COPD in BC between September 2020 and March 2021. We aimed to understand how access to healthcare for these conditions was affected during the pandemic. The survey asked respondents to report their characteristics, access to healthcare for asthma and COPD, types of services they found disrupted and telehealth (telephone or video appointment) use during the pandemic. We analysed 433 responses and found that access to healthcare for asthma and COPD was lower during the pandemic than pre-pandemic (p < 0.001). Specialty care services were most frequently reported as disrupted, while primary care, home care and diagnostics were least disrupted. Multivariable logistic regression revealed that access during the pandemic was positively associated with self-assessed financial ability (OR = 22.0, 95% CI: 7.0 - 84.0, p < 0.001, reference is disagreeing with having financial ability) and living in medium-sized urban areas (OR = 2.3, 95% CI: 1.0 - 5.2, p = 0.04, reference is rural areas). These disparities in access should be validated post-pandemic to confirm whether they still persist. They also indicate the continued relevance of exploring approaches for more equitable healthcare.

COVID-19 and the Latinx Community: "Promotoras Represent a Community in Pain".

COVID-19 has disproportionately affected the Latinx community, leading to heightened economic instability and increased mortality/morbidity. Frontline community health workers (promotoras) have played an integral role in serving low-income Latinx immigrant communities, disseminating health information to this vulnerable community while also facing heightened risks to their own health and wellbeing. This study explores the impact of the pandemic on Latinx communities and the promotoras that serve them, examining how the stresses and inequities the pandemic wrought might be mitigated. Promotoras (N = 15, all female) were recruited from a local health agency in Santa Ana, CA and completed a semi-structured interview about their experiences during COVID-19. Qualitative analyses demonstrated that the pandemic substantially affected the daily lives both of community members, via economic challenges, limited access to reliable pandemic-related information, and psychological and social stress, and of promotoras, via changes to the nature of their work and psychological and social stress. Promotoras perceived that these harms might be mitigated by providing for economic and material needs in the community, and that promotoras can be fortified to continue serving the community through self-care and psychosocial healing practices. According to promotoras, the Latinx community needs economic and material resources to overcome COVID-19 related stressors. Additionally, promotoras may benefit from programming to preserve mental and physical health in the wake of new stressors. Lending greater support to promotoras within the agencies in which they are nested may enable them to be more successful in fulfilling their mission and sustaining their own health.

Developing a sampling methodology for timely reporting of population-based COVID-19-associated hospitalization surveillance in the United States, COVID-NET 2020-2021.

BACKGROUND: The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) required a sampling methodology that allowed for production of timely population-based clinical estimates to inform the ongoing US COVID-19 pandemic response. METHODS: We developed a flexible sampling approach that considered reporting delays, differential hospitalized case burden across surveillance sites, and changing geographic and demographic trends over time. We incorporated weighting methods to adjust for the probability of selection and non-response, and to calibrate the sampled case distribution to the population distribution on demographics. We additionally developed procedures for variance estimation. RESULTS: Between March 2020 and June 2021, 19,293 (10.4%) of all adult hospitalized cases were sampled for chart abstraction. Variance estimates for select variables of interest were within desired ranges. CONCLUSIONS: COVID-NET's sampling methodology allowed for reporting of robust and timely, population-based data on the clinical epidemiology of COVID-19-associated hospitalizations and evolving trends over time, while attempting to reduce data collection burden on surveillance sites. Such methods may provide a general framework for other surveillance systems needing to quickly and efficiently collect and disseminate data for public health action.

Multicenter Diagnostic Evaluation of a Novel Coronavirus Antigen Lateral Flow Test among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 103 PFU/mL (Alpha), 2.5 × 102 PFU/mL (Delta), 2.5 × 103 PFU/mL (Gamma), and 1.0 × 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 104 copies/mL, 9.0 × 105 copies/mL, 1.7 × 106 copies/mL, and 1.8 × 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods. IMPORTANCE Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.

Overview of the Extrapolation of Pediatric Efficacy, or Children May Not Be Little Adults But They Are Not Space Aliens

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

Psychosocial impact of COVID-19 on female youth cheerleaders

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.

Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity had no antiviral effects but moderately reduced lung inflammation.

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.

Strategies to implement SARS-CoV-2 point-of-care testing into primary care settings: a qualitative secondary analysis guided by the Behaviour Change Wheel.

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.

Emergency urology procedures during CIVID-19 pandemic: A 2 monthly prospective study

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.

Point of care testing using rapid automated antigen testing for SARS-COV-2 in care homes – an exploratory safety, usability and diagnostic agreement evaluation

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.

The impact of COVID-19 on people ageing with an intellectual disability in Ireland: Protocol for a follow-up survey

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.

Resident Physician Perspectives on the Impact Of COVID-19 on Professional Interpersonal Relationships and Workplace Social Capital: A Qualitative Study

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]

The impact of physical distancing on the health and well-being of kuia and koroheke

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.

Maternal exposure to hydroxychloroquine and birth defects.

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.