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Aims The COVID-19 pandemic triggered a national lockdown to be imposed in the UK in March 2020. Social restrictions resulted in children being isolated within their homes with little to no contact with teachers, social workers, or health services. These measures decreased the opportunity to detect children suffering from abuse.1 Nationally, social restrictions contributed to 8,500 fewer referrals to children's services during COVID-19.2 Increased financial strain3 alongside domestic violence4 is suggested to have potentiated an increase in child abuse during the COVID-19 pandemic. This study therefore aimed to assess how COVID-19 affected child protection referrals in Leeds and evaluate the concern that the COVID-19 pandemic resulted in more child abuse yet fewer child abuse referrals. 2,5-7 Methods Referrals to Leeds Community Paediatric Department between 1st March and 30th September 2019 and 2020 were collated using electronic patient records and in total 426 referrals were evaluated. The source, reason and outcome of referrals was recorded as well as the age, sex, ethnicity, number of siblings, and socioeconomic status of each child. The presence of domestic violence in the household as well as any prior interactions with children's services was recorded. Results There were 22.5% fewer referrals in 2020 during the pandemic when compared to 2019, with a reduction in referrals from every source. The percentage of children with domestic violence in their household rose significantly from 44.58% in 2019 to 58.60% in 2020. The age of children referred differed significantly between 2019 and 2020. The modal age of children referred in 2019 was four years whereas in 2020 it was one year. Conclusion The number of referrals for suspected child abuse decreased in Leeds during COVID-19. It is therefore likely that child abuse became less visible rather than less prevalent during this pandemic.
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The COVID-19 pandemic has affected college students' basic needs, financial security, academic success, caregiving responsibilities, mental health, and more, according to the Fall 2020 Student Financial Wellness Survey (SFWS) conducted by Trellis Company. Researchers surveyed 37,936 students at 62 two-and four-year colleges and universities from October to November 2020 and found 53 percent (n=20,095) indicated one or more forms of basic needs insecurity (BNI). This brief examines data from students with BNI with a special lens on their mental health, familial responsibilities and finances, employment, and financial security. These results highlight the disparate impacts of the pandemic among basic needs insecure students.
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The ICH E9(R1) addendum on Estimands and Sensitivity Analyses in Clinical Trials has introduced a new estimand framework for the design, conduct, analysis, and interpretation of clinical trials. We share Pharmaceutical Industry experiences of implementing the estimand framework in the first two years since the final guidance became available with key lessons learned and highlight what else needs to be done to continue the journey in embedding the estimand framework in clinical trials. Emerging best practices and points to consider on strategies for implementing a new estimand thinking process are provided. Whilst much of the focus of implementing ICH E9(R1) to date has been on defining estimands, we highlight some of the important aspects relating to the choice of statistical analysis methods and sensitivity analyses to ensure estimands can be estimated robustly with minimal bias. In particular, we discuss the implications if complete follow-up is not possible when the treatment policy strategy is being used to handle intercurrent events. ICH E9(R1) was introduced just before the start of the COVID-19 pandemic, but a positive outcome from the pandemic has been an acceleration in the adoption of the estimand framework, including differentiating intercurrent events related or not related to the pandemic. In summary, much has been learned on the estimand journey and continued sharing of case studies will help to further advance the understanding and increase awareness across all clinical researchers of the estimand framework.
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COVID-19 Drug Treatment , Medicine , Data Interpretation, Statistical , Humans , Pandemics , Research DesignABSTRACT
Background. There are few real-world data on the use of remdesivir (RDV) looking at timing of initiation in relation to symptom onset and severity of presenting disease. Methods. We conducted multi-country retrospective study of clinical practice and use of RDV in COVID-19 patients. De-identified medical records data were entered into an e-CRF. Primary endpoints were all-cause mortality at day 28 and hospitalization duration. We assessed time from symptom onset to RDV start and re-admission. We included adults with PCR-confirmed symptomatic COVID-19 who were hospitalized after Aug 31, 2020 and received at least 1 dose of RDV. Descriptive analyses were conducted. Kaplan-Meier methods were used to calculate the mortality rate, LogRank test to compare groups defined by severity of disease. Competing risk regression with discharge and death as competing events was used to estimate duration of hospitalization, and Gray's test to compare the groups. Results. 448 patients in 5 countries (12 sites) were included. Demographics are summarized (table) by 3 disease severity groups at baseline: no supplemental oxygen (NSO), low flow oxygen ≤6 L/min (LFO), and high-flow oxygen > 6L/min (HFO). No demographic differences were found between groups except for the higher percentage of cancer/chemotherapy patients in NSO group. Corticosteroids use was HFO 73.6%, LFO 62.7%, NSO 58.0%. Mortality rate was significantly lower in NSO, and LFO groups compared with HFO (6.2%, 10.2%, 23.6%, respectively;Fig1). Median duration of hospitalization was 9 (95%CI 8-10), 9 (8-9), 13 (10-15) days, respectively (Fig2). Median time from first symptom to RDV start was 7 days in all 3 groups. Patients started RDV on day 1 of hospitalization in HFO and LFO and day 2 on NSO groups. And received a 5 day course (median). Readmission within 28-days of discharge was < 5% and similar across all 3 groups. Conclusion. In this real-world cohort of COVID-19 positive hospitalized patients, RDV use was consistent across countries. RDV was started within a median of 7 days from symptom within 2 days of admission and given for a median of 5 days. Higher mortality rate and duration of hospitalization was seen in the HFO group and similar rates seen in the LFO and NSO groups. Readmission was consistently low across all 3 groups.
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Background. SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods. ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results. Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion. BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease.
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Keywords: Simulation;Respiratory;Education Purpose: On-call physiotherapy can be a daunting and stressful experience. The aim of the high fidelity simulation suite in clinical education is to practice true to life on-call scenarios in a safe, supported and non-judgemental environment. The objectives included: increasing confidence in assessing and treating acutely unwell deteriorating patients;improving communication between physiotherapy colleagues and the MDT and escalating care appropriately. Methods: Six case studies were designed to replicate a true to life situation to challenge clinical reasoning and help improve confidence in an on-call situation. A simulation co-ordinator was present during the simulation to act as the nurse on duty. The participants were encouraged to communicate with each other and work together. They could ask the nurse questions and the control room could feedback the information. The facilitators in the control room observed the simulation, changed clinical observations in response to treatments and responded as the patient through a microphone. The simulation was fluid and whilst it was designed to target specific clinical skills, if clinically reasoned the participants could use any treatments that they felt were appropriate. Colleagues watched the simulation from a viewing room and made notes to feedback to their peers. After the simulation, a de-brief was carried out to enable participants to reflect on the scenario in the form of facilitated discussion to share learning from each other. Results: We have successfully completed 6 scenarios with 20 physiotherapists. Reflections were completed via a group de-brief and participants were given the opportunity to complete a structured reflection for continuing professional development. Participants’ feedback in response to the simulation was very positive, reporting to be “just right” in terms of skill level and beneficial to their clinical and professional development. It has increased participants confidence in assessing and treating acutely unwell patients as well as highlighting the importance of escalating care to the appropriate members of the multi-disciplinary team, identifying strategies for effective communication. Conclusion(s): The experiences created an open learning environment in which mistakes were not judged but lead to a greater potential for continuing professional development via self-reflection and peer reviews. Whilst some found the experience daunting and uncomfortable it has the potential to increase skills, knowledge and confidence, similar to the findings by Mansell, Harvey and Thomas, 2019. High fidelity simulation could increase skills of non-on-call physiotherapy staff quickly to help meet workforce requirements demanded by surges to service demand such as the COVID-19 pandemic. This has highlighted the need to transform clinical education to improve service provision and delivery of on-call physiotherapy service and enhance patient experience. Further investigation is warranted to identify how high fidelity simulation could also enhance collaborative working within the multi-disciplinary team in acutely unwell patients. Impact: The project can be used as evidence for the use of high fidelity simulation I on-call physiotherapy training for: increasing respiratory competence of newly qualified physiotherapists and students;upskilling non-on-call physiotherapists according to workforce requirements and improving multi-disciplinary team working. Funding acknowledgements: Not funded.
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Scientists, governments, and pharmaceutical companies face significant obstacles to global adoption of COVID-19 vaccines. Chief among these challenges are public fear of vaccine-related injury and manufacturers' fears of liability arising from those injuries. Through the lens of the COVID-19 pandemic, we explore the history and current landscape of liability related to vaccines, and we propose potential solutions to the challenges of ensuring widespread adoption of vaccines. Part II provides background on vaccine development, discussing the challenges of achieving herd immunity a situation in which sufficient numbers of a community are vaccinated and thus immune, leading to containment or eradication of an infectious disease and the history of and obstacles to implementing mandatory vaccination policies in the United States and around the world. Against this historical backdrop, Part III summarizes and critiques the steps taken in the United States and globally to address liability related to the development and release of vaccines, including for COVID-19. It describes how vaccine-related liability has discouraged pharmaceutical companies from developing vaccines and how various countries have mitigated this risk and spurred innovation by establishing vaccine injury compensation programs. Part III discusses the Vaccine Injury Compensation Program (VICP) in the United States, which compensates people injured by vaccines, and no-fault vaccine compensation regimes that other countries around the world have implemented. And it discusses the invocation of the Public Health Emergency Preparedness Act (PREP Act) and the issuance of Declarations by the Secretary of Health and Human Services in response to the COVID-19 pandemic as a way to provide immunity to vaccine manufacturers. Although PREP provides expansive immunity, it does not prevent litigants from bringing suit, and those invoking PREP will have to litigate their entitlement to its protections. Finally, Part III discusses vaccine liability in the context of three previous pandemics: H1N1, Ebola, and Dengue fever in the Philippines. Part IV provides an overview of the skepticism about the effectiveness and safety of vaccines, exploring historical examples of vaccine controversy. In particular, it discusses public perceptions of vaccines and the impact of the decision by the Centers for Disease Control and Prevention (CDC) to withdraw its recommendation for the RotaShield vaccine. Finally, Part V offers recommendations aimed at establishing a more effective injury compensation regime designed to encourage innovation and swift adoption of vaccines and other pandemic responses. In this section, we discuss the importance of global coordination in limiting liability. We propose three strategies for establishing a global vaccine-injury compensation scheme: a global treaty, a third-party intermediary declaration modeled after the PREP Act, and letters of agreement modeled after the response to H1N1. In addition, in the United States, we recommend reforms to the VICP so that this system can accommodate claims related to COVID-19 vaccines. To ensure the prompt adoption of effective vaccines so as to achieve herd immunity, we recommend developing enforceable and near-mandatory vaccination requirements. And we propose strategies for addressing two related hurdles that have previously stymied vaccine development and pandemic preparedness: global amnesia, which describes the collective forgetting of key details of a public health crisis once a situation has resolved, and hindsight bias, which describes the tendency to misjudge, after-the -fact, the challenges and uncertainties experienced during a crisis.