ABSTRACT
Much home learning research explores the benefits from the perspectives of the child or staff. Less is written about how parent’s view home learning. This became more noticeable recently when nurseries closed because of Covid-19 lockdown. Staff had to design digital home learning activities at speed to help parents support their children’s learning and development while maintaining their relationships with parents. However, we realised we did not know enough about what parents would find helpful and decided to seek their views to categorise their perspectives of home learning and therefore provide more relevant home learning. This paper records a small-scale explorative study in a group of 9 London nurseries where using ethnographic interviews, we sought the views of 15 sets of parents. The study presented some early evidence that parent’s views of home learning can be categorised and suggests an emerging typology made from four groups of parents whose views of home learning reflect their levels of confidence and experience but for some, their views appear to be filtered through the current public debate in England about school readiness. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
ABSTRACT
Background: Acute COVID-19 is associated with marked endotheliopathy, VWF-ADAMTS13 axis imbalance and abnormal pulmonary angiogenesis. Persistent endotheliopathy and elevated VWF levels have also been reported in convalescent COVID-19 patients. Aim(s): We investigated the hypothesis that altered pulmonary microvascular architecture may persist in COVID-19 convalescence, resulting in ongoing endothelial cell (EC) activation and VWF-ADAMTS13 axis imbalance, possibly contributing to Long COVID pathogenesis. Method(s): 50 patients (median age 50 years, 60% male, median 68 days post acute COVID-19) were reviewed. Six-minute- walk tests (6MWT) were performed (median 6MWT distance 430m) and plasma samples collected. Plasma VWF:Ag and ADAMTS13 levels were measured by ELISA, and angiogenesis markers assessed by membrane-based antibody array. Result(s): Plasma VWF:Ag levels were significantly elevated in convalescent COVID-19 patients compared to controls (1.1 vs. 0.84 IU/ml;p = 0.004), with 30% (15/50) having VWF:Ag levels above the upper limit of normal. In contrast, plasma ADAMTS13 was significantly reduced in convalescent COVID-19 (median 467 ng/ml vs. 636 ng/ ml p < 0.001). ADAMTS13 levels were significantly lower in those who required hospitalization for acute COVID-19 compared with those managed as outpatients (median 454 ng/ml vs. 513 ng/ml, p = 0.04). Overall, the VWF/ADAMTS13 ratio was significantly elevated in convalescent COVID-19 compared with controls (2.1 vs. 1.1 p = 0.0002) and interestingly was elevated in patients with reduced 6MWT distance (distance >=430 m or <430 m: 1.8 vs. 2.4, p = 0.02). In total, 15 angiogenesis markers were elevated in convalescent COVID-19 compared to controls. An additional 17 angiogenesis (Figure Presented) markers were unique to convalescent COVID-19 and were not found in control plasma (Table 1). Conclusion(s): Collectively, these novel findings demonstrate that endotheliopathy is sustained for months following acute COVID-19 in some patients. As a result, plasma VWF levels are significantly increased;ADAMTS13 levels reduced, and there is ongoing dysregulation of angiogenesis. Further studies will be required to define whether these alterations play a role in Long COVID pathogenesis.
ABSTRACT
Background: Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined. Aim(s): We investigated EC activation in patients with acute COVID-19, and in particular focused on how proteins stored within Weibel-Palade bodies (WPBs) may impact key aspects of disease pathogenesis. Method(s): 39 patients with confirmed COVID-19 were recruited. Weibel-Palade body biomarkers [von Willebrand factor (VWF), angiopoietin-2 (Ang-2) and osteoprotegerin (OPG)] and soluble thrombomodulin (sTM) levels were determined. In addition, EC activation and angiogenesis were assessed in the presence or absence of COVID-19 plasma incubation. Result(s): Markedly elevated plasma VWF:Ag, Ang-2, OPG and sTM levels were observed in acute COVID-19 patients. The increased levels of both sTM and WPB components (VWF, OPG and Ang-2) correlated with COVID-19 severity. Incubation of COVID-19 plasma with ECs triggered enhanced VWF secretion and increased Ang-2 expression (Figure 1). In keeping with the autopsy reports of intussusceptive angiogenesis, treatment with COVID-19 plasma also caused significantly increased EC angiogenesis (Figure 1). Conclusion(s): We propose that as COVID-19 develops, progressive loss of TM and increased sTM, as well as increased Ang-2 expression result in loss of EC quiescence, WPB exocytosis, and a local pro-angiogenic state.
ABSTRACT
Introduction: Prone positioning is commonly used when treating ventilated Covid-19 patients. Whilst there have been some reports of ICU proning-related injuries to the brachial plexus well before the pandemic (Goettler et al. 2002), it is usually a very uncommon complication. Despite guidance from the Faculty of Intensive Care Medicine on the care of the proned patient, cases of peripheral neuropathies following ICU admission have significantly increased during the Covid-19 pandemic at our centre (Miller et al. 2021). Nerve injury is associated with reduced quality of life, impaired activity participation and persistent pain (Bailey et al. 2009). Objectives: The aim of this quality improvement project was to identify the effect that new guideline development and related healthcare professional education had on the number and severity of peripheral neuropathies identified following Covid-19 ICU admission. Methods: Between March 2020 and May 2021, we collected clinical data from patients who sustained peripheral neuropathies during their inpatient stay for Covid-19. Data were collected via face-to-face patient assessments within acute nerve clinics or post-ICU rehabilitation wards. A grading system was used to categorise the peripheral nerve injuries into severe, intermediate and mild (Power et al. 2020). Electronic ICU clinical noting was examined to identify the frequency and duration of each proning episode for each patient who presented with nerve injury. Following the first surge in 2020 updated proning guidelines were developed with ICU team leaders and disseminated. This involved face-to-face education of frontline staff. Results: At our centre 93 patients survived Covid ICU between March -June 2020 (surge 1) and 21 of those sustained nerve injury (22.58%). 309 patients survived Covid ICU between September 2020 -May 2021 (surge 2) and 12 of those sustained nerve injury (3.88%). For patients who sustained nerve injury, the average number of prones changed between surges from 6 to 13. The average duration of each episode of proning changed from 17.8hrs to 18.6hrs. Despite the increase in prone frequency, nerve injury occurrence reduced (proportionate to the number of patients who survived Covid ICU) by 82%. 14/21 (66%) injuries acquired in the first surge were of high grade and 4/ 12 (33%) were of high grade during the second surge. Conclusion: Optimising positioning of the proned ventilated patient may reduce the incidence of nerve injury. However, we must also acknowledge that changes in medical management between surges (i.e. use of dexamethasone, remdesivir) may have contributed to this. Individuals still developed severe injury despite this change in practice. Further research looking into risk factors and further methods of optimising the prone positioning on ICU is warranted to reduce the occurrence of this potentially life-changing injury.
ABSTRACT
Introduction A global trial is currently investigating the impact of high-intensity interval training (HIIT) on survival in advanced prostate cancer (the INTERVAL trial). To ensure greater accessibility, we designed a parallel trial (EXACT), to determine the feasibility of exercise in those contraindicated to HIIT. Methods Men with metastatic castrate-resistant prostate cancer being actively treated with androgen deprivation therapy and a novel hormone therapy (abiraterone acetate or enzalutamide) are eligible to participate in 12- weeks of home-based walking and strengthening. Participants complete physical (e.g. 6-min walk test and timed sit-to-stand) and quality of life (e.g. BPI-SF;EQ-5D-5L;FACIT-fatigue;FACT-P) outcomes at baseline (T1), 12 (T2) and 24 weeks (T3). This trial was adapted to enable remote recruitment and delivery during the COVID-19 pandemic. Results To date, 118 patients have been screened, with 33 approached by their clinician to participate. 25 patients have consented, with 12 completing the trial without any intervention-related adverse events and 6 withdrawn. Recruitment and trial delivery was operational throughout the COVID-19 pandemic. Currently positive trends are evident for physical and quality of life outcomes at T2 and T3. Conclusions Although this trial is ongoing, early trends suggest this intervention is safe and feasible for men with advanced castration resistant prostate cancer and could improve physical capacity and quality of life.
ABSTRACT
Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120;interquartile range [IQR] 60-300) but randomized (75.8%;n=522) and were often conducted in China (51.1%;n=352) or the USA (11%;n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112);78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273;IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%;3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample;27 between 20-50%;and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats.