Developing and evaluating the Digitally Enhanced Liberation from VEntilation (DELVE) system: A study of feasibility and user acceptance

Introduction: In common with many aspects of critical illness recovery, there is no universally accepted formula for "weaning," the term used to describe the process of liberating patients from mechanical ventilation.1-3 Understanding a patient's progress during a prolonged wean can be difficult and requires integration of various datasets. Therefore, it is good practice to ensure that weaning prescriptions are clear, easy to follow and adhered to and that weaning-associated data and meta data are recorded accurately and are easy to interpret. The prototype Digitally Enhanced Liberation from VEntilation (DELVE) system has been designed to be used in combination with the Puritan Bennett(TM) 980 (PB980) ventilator (Covidien, USA). DELVE is an open-loop system which provides an interactive weaning chart, combining the weaning prescription entered by the clinical staff, with actual settings recorded from the ventilator in order to display compliance with the prescription (Figure 1). DELVE also collects measured data from the ventilator which could be used to display respiratory performance, both real-time and historical. Figure 1. DELVE set up with the PB980 ventilator (in the simulation suite). Objective(s): This feasibility study was designed to inform development of the first DELVE prototype and a future clinical trial to determine clinical effectiveness and usefulness. The study objectives were to determine whether DELVE could: 1. Present a digital weaning chart that staff could use effectively and would be superior to the current paper version. 2. Record and display the patients' ventilatory performance, both real time and historical, during liberation from mechanical ventilation. Method(s): This was a mixed-methods, prospective feasibility study of a complex intervention.4 Ventilated patients with a tracheostomy, commencing the weaning process, were recruited from an adult intensive care unit. DELVE was used alongside the current paper-based system for weaning planning and data collection. Patients remained in the study until they no longer required the support of the PB980 ventilator. Result(s): Twenty patients were enrolled for between 25 and 270 hours each. There were no safety incidents or data breaches. DELVE was successfully operated by staff, who were able to connect DELVE to the ventilator, prescribe weaning plans and analyse adherence. The digital weaning chart user interface was intuitive and easy to navigate. It was clearer, more complete and easier to interpret when compared to the paper weaning charts (Figure 2). DELVE reliably collected data every ten seconds and safely stored over six million items of measured data and 25000 events, such as alarm triggers and setting changes, in a form that could allow analysis and pictorial or graphical presentation. Conclusion(s): This study supported the feasibility of this and future versions of DELVE to present both a digital weaning chart and to facilitate visual and numerical data presentation. Future iterations of the system could include a user-friendly dashboard representing patient progress during the weaning process. Assimilation of large volumes of data could be used to enhance understanding and inform decision making around the prolonged wean.

Exploring the impact of comorbidities in individuals after a Covid hospital admission or community infection in those referred to a rehabilitation programme

Introduction: Following a SARS-CoV-2(COVID)infection,individuals often present with complex needs and multiple comorbidities. However, it is currently unknown if comorbidities differ between those who were hospitalised or remained in the community during their covid infection. Aim(s): To explore the baseline characteristics and impact of comorbidities in individuals who were hospitalised or managed their covid infection at home and referred into a Covid Rehabilitation programme (CoR). Method(s): An observational cohort analysis of individuals who attended a CoR assessment between July 2020 and November 2021. Routine characteristics including age, gender, BMI, ethnicity and significant comorbidities were collected. Result(s): 466 individuals (age: 54 +/- 14 yrs;BMI:7.4 +/-30kg/m ;Female: 271[58%],White British: 296[64%], South Asian:111[26%],Other Ethnic groups:36[9.1%])were assessed. Those who were hospitalised had more comorbidities than those in the community;Median IQR1(1-2) vs 2 (1-4);p<0.05. The top 5 comorbidities were different in each group;Hospital: Total 544;Respiratory (n=101;18.6%), Metabolic (100;18.4%), Vascular (79;14.5%), MSK (72;13.2%), Psychiatric (71;19%) and Community: Total: 391;Psychiatric (97;25%), MSK (72;19.5%), Respiratory (74;19%), Metabolic (38;9.7%), Gastroenterology (38;9.7%). Conclusion(s): Patients who were hospitalised had more comorbidities than the community referrals. It will be important to consider these comorbidities when assessing for and delivering CoR.

Mapping UK rehabilitation provision for adults after hospital admission with COVID-19

Introduction: NICE guidance (2020) for Long Covid calls for a comprehensive assessment and, where appropriate, referral to rehabilitation. Our aim was to explore characteristics of rehabilitation programmes (RP) for patients in the UK. Method(s): Rehabilitation specific information was extracted from a survey of sites taking part in the PHOSP-COVID study (https://www.phosp.org/), Feb 2020-Mar 2021. Data included professions and services involved, content, outcome measures and model used. Data was recorded on JISC and exported to Excel. Result(s): 32/45 sites had access to RP, half was covid specific RP. 22 provided content information. Most RP were delivered by the same organisation providing post-hospitalisation review, 19/22 used more than one model of delivery. Models included face to face, virtual, digital platforms and home-based models. Decisions on how to deliver RP depended on available staff, service pressures, safety and patient preference. RPs delivered most often by Allied Health Professionals and existing Pulmonary Rehabilitation services (16 services), 3 single profession. Not all RPs matched outcome measures to components delivered, Figure1. Conclusion(s): 2/3rds of sites were able to access either covid or non-covid specific MDT rehabilitation. There is heterogeneity in the assessment and content of rehabilitation delivered, as well as the model of delivery.

Efficacy of a Polyclonal Ovine Fab (PR020) Against SARS-CoV-2 Infection

Background. Passive immune therapies may be useful in mitigating severe COVID-19. The hamster model has been successfully used to study efficacy of COVID-19 treatments. Our objective with this research is to demonstrate initial efficacy of a new polyclonal ovine Fab raised against the SARS-CoV-2 spike protein (PR020) as a treatment for COVID-19. Methods. Hamsters were treated with PR020 via intraperitoneal route at a dose of 120 mg/kg or a vehicle control once every 24 hours for 8 days, starting 1 day prior to viral challenge with Victoria/1/2020 SARS-CoV-2. Sampling to detect viral RNA and clinical observations were taken throughout the challenge phase. Necropsy occurred 1 day following the last dose of PR020, and tissues were assessed for histopathology and viral RNA. Results. Hamsters receiving vehicle alone lost weight more rapidly than the PR020 group (Figure 1, p< 0.05 day 4 onward). Clinical illness scores for the PR020 group were lower compared to control animals (Figure 2, p< 0.05 day 3 onward). While viral shedding assessed by throat swab did not differ between groups, viral RNA levels in lung tissue was significantly lower in PR020-treated animals (Figure 3, p< 0.05). PR020-treated animals also showed significantly less pathological changes in the lung compared to controls (Figure 4, p=0.0022). (Figure Presented) Conclusion. Treatment with PR020 resulted in a positive clinical outcome (e.g. less weight loss and lower clinical signs). While treatment appeared to have little effect in the nasopharynx, there was a positive effect in the lower respiratory tract, with substantially less viral RNA in the lungs of the group given PR020 and a decrease in the lung histopathology, including consolidation.

Advice and Guidance: An effective communication tool between primary and secondary care in the COVID era?

Introduction: Advice and Guidance is a digital communication tool that allows primary care physicians to seek advice from secondary care clinicians prior or instead of direct referrals. Aim(s): Our audit aims to analyse The number of Advice and Guidance e-referrals made to General Surgery consultants at The Queen Elizabeth Hospital Birmingham and measure The outcomes of those conversations in order to determine The usefulness and value of The given platform as well as analyse The timescale of The replies. Method(s): We have retrospectively analysed The outcomes of all The referrals to General Surgery made via Advice and Guidance platform between July 2020 and September 2021. The responses were categorised into 7 different outcomes, main ones being "outpatient clinic referral", "further investigation required", "advice from a different specialty is needed" and "advice on management only". Time taken to reply to The referrals was also analysed. Result(s): At total of 2244 referrals were included in this audit. 61% of The referrals were deferred to outpatient clinic for further review, 18% required further investigations, in 10% advice only was given and 8% were referred to a different specialty. Time taken to reply to a referral was 5 days on average. Conclusion(s): Advice and Guidance is an appropriate tool that allows direct communication between Gps and General Surgical consultants and is set to reduce The number of unnecessary outpatient clinic referrals made. This in turn reduces pressure on The already stretched secondary care system, especially in The ongoing COVID-19 pandemic.

A role for Von Willebrand Factor-ADAMTS13 axis imbalance and abnormal angiogenesis in long COVID syndrome

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.

Endothelial cell activation, Weibel-Palade body secretion and enhanced angiogenesis in severe COVID-19

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.

Impact of COVID-19 on newborn screening in South Texas

Introduction: Newborn screening programs endeavor to rapidly screen and promptly diagnose and treat various conditions, including many inborn errors of metabolism, in order to avoid or minimize morbidity and mortality. All infants in Texas are required to have a first newborn screen at 24–48 hours of life and a second at 10–14 days of age. In Texas, there is a single state laboratory that performs all testing;confirmatory testing is left to primary care providers to do alone or in consultation with the metabolic center of their choice. In 2019, Texas screened over 380,000 babies, including over 737,000 specimens, and identified 850 affected infants. The arrival of the novel coronavirus, known as SARS-CoV-2 (COVID-19), in 2020 had an immense impact on medical care, resulting in clinic closures, telemedicine expansion, and limited staffing. These changes, as well as delays in other areas of healthcare, raised concerns that the timeliness of newborn screening could also be affected, whether by delays in the state laboratory, slower sample delivery, difficulty scheduling patient evaluations, or parental hesitation to seek care due to exposure risk. We hypothesized that diagnosis of metabolic disease by newborn screening was slowed by the pandemic. Methods: We analyzed all cases referred to our metabolic service at Texas Children’s Hospital for abnormal screening prior to disruption of normal hospital activity by the pandemic (January 1, 2020–March 15, 2020) and those referred after disruption of normal hospital activity (March 16, 2020–May 6, 2020). We excluded patients whose testing was incomplete at the time of the analysis and those that followed up at a different institution. We calculated the time to reporting of the first newborn screen (NBS1) and second newborn screen (NBS2), the number of days from the abnormal NBS to all confirmatory labs drawn (LD), the number of days from LD to the return of all results (RR), and the number of days from the abnormal NBS to diagnosis or clearance (DX) for each patient. We averaged and compared these values for the pre-pandemic group (N = 84) and pandemic group (N = 42) using Microsoft Excel, running an F-test two sample for variance and t-test two sample assuming unequal variance for each category as well as calculating the standard deviation. Results: We found no statistical difference in any category for the patients born prior to the COVID-19 pandemic impacting our clinic activities and those referred afterward (Figure 1). The age at reporting NBS1 was 6.7 ± 2.2 days pre-pandemic, versus 7.2 ± 1.4 in the pandemic group (p = 0.12). For NBS2, the age was 26.9 ± 28.6 days in the pre-pandemic group and 24.5 ± 16.5 in the pandemic group (p = 0.58). The LD was longer in the pandemic group (5.8 ± 8.8 days pre-pandemic vs 10.9 ± 30.1 days during pandemic), but this difference was not statistically significant (p = 0.29). In contrast, the RR was shorter during the pandemic with averages of 9.2 ± 5.1 days pre-pandemic versus 7.5 ± 4.2 during pandemic. This difference was close to but did not meet statistical significance (p = 0.055). Finally, the DX, perhaps the most important parameter we assessed, also did not demonstrate a significant difference with averages of 29.8 ± 23.2 days in the pre-pandemic group and 34.5 ± 35.9 days in the pandemic group (p = 0.47). Conclusions: No significant difference in any measured parameter was noted between newborns born before clinic activities were affected by the COVID-19 pandemic compared to those born afterward. This is reassuring that the newborn screening program in South Texas remained robust, despite no formal or financial relationship between the state laboratory and regional metabolic centers. We acknowledge the limitations of this study, including its conduction at a single center early in the period of clinical activities being impacted. However, we would expect that the most significant difference would have occurred at the beginning of the pandemic, during the limitation of in person visits and prior to the deve opment of alternative strategies and re-opening of clinics and labs. The extended course of newborn screening and confirmatory testing resulted in the exclusion of more patients in the pandemic group as their testing was still pending at the time of data collection, limiting the power in analysis of this group. Significant variability in both groups (as evidenced by the high standard deviations) could mean that significant outliers are skewing the data and that statistically significant differences could exist. Overall, though, it seems that the pandemic did not adversely affect various metrics regarding newborn screening at our center.(Figure Presented)

The impact of post COVID-19 rehabilitation on hospital and non-hospitalised participant- is there a difference?

P70 Table 1 All Hospitalised Mean difference (SD) Non-Hospitalised Mean difference (SD) Between group Difference Mean difference (95% CI) ISWT(m) 100.1(95.6)** 95.5(90.0)** 114.4(112.8)** 18.9(70.7,-32.9) ESWT(secs) 332.0(636.9)** 308.0 (686.4)** 417.2(422.2)** 109.1 (470.0, -251.7) QMVC (kg) 5.2(4.8)** 5.6(4.7)** 3.7(5.5) 1.9 (2.2,-6.0) FACIT 3.8(7.8)** 3.4 (7.4)* 5.1(9.2)* 1.8 (-2.6,6.2) CAT 2.6(6.0)** 2.8(5.6)** 0.7(7.2) 2.1 (5.4,-1.1) EQ-5D (thermometer) 7.7(20.1)** 11.0(19.4)** 3.9(19.0) 14.9 (3.2, 26.6)* MoCA 0.8(3.8) 0.8(4.2) 0.7(1.9) 0.08(2.2,-2.4) HAD-A 0.6(3.1) 0.6(3.0) 0.4(3.3) 0.2 (1.5,-2.0) HAD-D 1.1(3.5)* 1.3(3.4)* 0.5(3.8) 0.8(1.2,-2.7) *<0.05 **<0.01ConclusionEarly data suggests that those who have prolonged and significant symptoms post COVID-19 improve after a supervised rehabilitation programme. The response to the intervention is similar in both hospitalised and non-hospitalised groups. This is early cohort data and therefore must be treated with caution, nevertheless is encouraging.

Remote delivery options for self-management programmes for patients with COPD during the COVID-19 pandemic. Uptake, completion and clinical outcomes

P65 Table 1Change in… TP SM SW CAT -2.4 * C -3.1 * C - 7.2 C CRQ- Dyspnoea 0.8 * C 0.5 * C 1.1 * C CRQ- Fatigue 0.4 * 0.8 * C 0.9 C CRQ- Emotion 0.4 * 0.8 * C 1.4 C CRQ- Mastery 0.6 * C 0.5 C 0.8 C *: Statistically significant p<0.05C: clinically relevant (meets MCID for this population)ConclusionMost patients chose bi-weekly telephone support, TP and SM had the highest completion rate. All options were equally effective in terms of clinical outcomes. Despite being clinically effective, more work is needed to promote completion in digitally delivered self-management programmes.