A Randomized, Controlled Trial of Trifarotene Plus Doxycycline for Severe Acne Vulgaris

OBJECTIVE: We evaluated the efficacy and safety of trifarotene plus oral doxycycline in acne. METHOD(S): This was a randomized (2:1 ratio) 12-week, double-blind study of once-daily trifarotene cream 50microg/g plus enteric-coated doxycycline 120mg (T+D) versus trifarotene vehicle and doxycycline placebo (V+P). Patients were aged 12 years or older with severe facial acne (>=20 inflammatory lesions, 30 to 120 non-inflammatory lesions, and <=4 nodules). Efficacy outcomes included change from baseline in lesion counts and success (score of 0/1 with >=2 grade improvement) on investigator global assessment (IGA). Safety was assessed by adverse events and local tolerability. RESULT(S): The study enrolled 133 subjects in the T+D group and 69 subjects in the V+P group. The population was balanced, with an approximately even ratio of adolescent (12-17 years) and adult (>=18 years) subjects. The absolute change in lesion counts from baseline were: -69.1 T+D versus -48.1 V+P for total lesions, -29.4 T+D versus -19.5 V+P for inflammatory lesions, and -39.5 T+D versus -28.2 for non-inflammatory lesions (P<0.0001 for all). Success was achieved by 31.7 percent of subjects in the T+D group versus 15.8 percent in the V+P group (P=0.0107). The safety and tolerability profiles were comparable between the T+D and V+P arms. CONCLUSION(S): T+D was demonstrated to be safe and efficacious as a treatment option for patients with severe acne.Copyright © 2022 Matrix Medical Communications. All rights reserved.

Brexit, COVID-19 and climate change: mapping the impact of the 'triple challenge' on health and well-being in wales

Brexit, COVID-19 and climate change pose challenges of national and global importance. They continue to have impacts across the economy, society, health, and the environment, all of which are determinants of health and well-being. Between 2018 and 2021, Public Health Wales undertook three Health Impact Assessments (HIA) in relation to the impact of the challenges in Wales. Based on these, work has been carried out to map the synergies across the 'Triple Challenge'. This paper highlights the commonalities in the impact of the three challenges for Wales, discusses the process carried out, learns from it and proposes actions that can be taken to mitigate harm. Results indicate the three components of the Triple Challenge must not be viewed as separate silos as they have cumulative multi-faceted impacts. This affects some population groups more negatively than others and present a 'Triple Challenge' to nation states in the UK and Europe. A HIA approach can enable a range of stakeholders to critically view similar challenges not just as single issues but as a holistic whole to mobilise action.

International Horizon Scanning the impact of Covid-19 on increasing the health gap and vulnerability : Liz Green

The COVID-19 pandemic has caused unprecedented challenges for populations, health systems and governments worldwide, which have resulted in lasting economic, social and health impacts. The results of such have been felt disproportionately throughout society and existing vulnerabilities have been highlighted and heightened. A clear understanding of the extent of these vulnerabilities is needed in order to fully address the problem. The World Health Organization Collaborating Centre on Investment for Health and Well-being (WHOCC), Public Health Wales has developed a summary report focusing on the existing and emerging inequalities resulting from the pandemic, as identified through international evidence and learning from the International Horizon Scanning Reports. These reports, undertaken between May 2020 - August 2021, are based upon rapid evidence synthesis reviews of international literature. The summary report focuses on global learning and best practices in order to better understand and address the unequal impacts of the pandemic. The information has been categorised according to the five essential conditions required to enable a healthy life as presented within the WHO health equity conditions framework. The report provides evidence on groups most vulnerable to both direct and indirect impacts of the pandemic as well as promising practice to address the resulting inequity. Inequalities and related factors explored within the report include but are not limited to, level of deprivation and education. Taking a global perspective, this report summarises international evidence to support inclusive, sustainable, and equitable solutions, such as protecting economic well-being and taking an intergenerational lens in both response and recovery. To address and mitigate the impact of the pandemic upon vulnerable groups, collating and sharing international evidence and best practice has proven to support equitable long-term socio-economic and environmental recovery. Key messages • International learning provides vital insights to support recovery in Wales and beyond. • Responses to the pandemic should address the needs of the vulnerable to reduce existing health gaps.

The health impact of the Triple Challenge of Brexit, COVID-19 and Climate Change in Wales : Liz Green

The COVID-19 pandemic has revealed the complex relationships between health, well-being, economy and society. The United Kingdom’s (UK) withdrawal from the European Union (Brexit) and climate change are having a cumulative, magnifying impact. UK nations have to tackle the multifaceted nature of Brexit, COVID-19 and climate change (‘Triple Challenge’ or TC) not only in isolation, but as a cumulative whole.This study provides a strategic overview of the interactions of the TC on determinants of health and equity in Wales and proposes opportunities to take forward. Using findings from existing Welsh Health Impact Assessments (HIAs) undertaken on the single challenges, rapid searches of the academic and grey literature were undertaken to identify evidence which focused on the TC and its impacts.From this, key determinants impacted and spotlight examples were identified and analysed. Evidence indicates the TC will have a wide range of compounding impacts across multiple determinants and inequalities. These will need to be viewed in synergy, not singularly. Determinants affected include i.e mental well-being, food insecurity, employment.Population groups potentially affected include rural communities, fishers/farmers, young people. Policy responses need to be constructed in an integrated way with cross sector involvement as actions intended to have positive impacts for one challenge could also have negative unintended impacts for others. This innovative work has highlighted the significant interconnectedness of the challenges. Developing an overarching policy approach could support lasting change.Having the TC as the underpinning focus point for new policies and strategies will help to maximise impact when addressing concerns in relation to post Brexit policy/actions, COVID recovery and climate change adaptation/mitigation.This work can be utilized by other nations as an example for challenges they may face in their context and nations in the UK/Europe affected by the TC. Key messages • Brexit, COVID-19 and climate change have cumulative health impacts which must be considered together. • Health impact assessment can provide a core framework through which to explore inequalities and health impact of multiple policy and practical issues.

Health impact Assessment practice in Wales: factors conditioning its success : Liz Green

Historically, Public Health Institutes (PHIs) were formed to address emergency public health and environmental health related challenges for example, infectious disease outbreaks and sanitary conditions which will affect health. The COVID-19 pandemic has demonstrated the importance and value of PHIs and the specific knowledge and expertise sat within them in the 21st century in relation to critical health issues. However, PHIs have also the potential expertise to look at the wider determinants of health and how they might affect population health and inequalities. In doing so, they play a critical role to advocate for Health in All Policies (HiAP) and Health Impact Assessment (HIA) by engaging with decision makers from health and non-health sectors and providing evidence and health intelligence. Public Health Wales (PHW) has conducted very complex studies as the HIA of the impact of Brexit on the population of Wales, which was praised as very useful by the Welsh Government and local decision makers at a time when, otherwise, little robust evidence-based information was available. Other positive HIA experiences are the recently published HIA about impacts of climate change or COVID-19 pandemic. Those achievements were possible thanks to the establishment of a specific unit dedicated to HIA within PHW, and to the political support and resources. This has built awareness raising and trust in HIA as a tool to support decision making from all sectors in Wales, enabled also by much training and stakeholder participation.

SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY B-CELL NON-HODGKIN'S LYMPHOMA (B-NHL), AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) / SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Background: We have previously described AUTO1, a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR T-cell immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL (Ghorashian S et al., Nat Med 2019;Roddie C et al., JCO 2021). This data confirms the intended function of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Aims: We have initiated testing of AUTO1 in the setting of B-NHL and CLL/SLL (NCT02935257). Methods: Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised patient leukapheresate. Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m x3) and cyclophosphamide (60mg/kg x1) prior to AUTO1 infusion, with the exception of the DLBCL cohort who additionally received a single dose of pembrolizumab (200mg) on day -1 to potentiate CAR-T expansion. AUTO1 dose varies based on the indication. Split dosing of 230 x106 CD19 CAR T-cells at day 0 and day 9 is employed in the CLL cohort. A single dose of 200 x106 CD19 CAR T-cells is delivered to patients with B-NHL. Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months. Results: As of 8th February 2022, we enrolled 23 patients: 11 low grade NHL (LG-NHL:7 with FL and 3 with MCL), 7 DLBCL and 5 CLL. Apheresis was successful in all 23 patients and product manufacture was successful in 22 (pending in the last). 19 patients were infused: 10 with LG-NHL, 6 with DLBCL and 3 with CLL. 1 CLL patient was pending infusion at time of data cut-off and 2 patients died pre-infusion: 1 MCL patient, from COVID-19 and 1 CLL patient, from intracerebral haemorrhage. Patients treated with AUTO1 had a median age of 60 years (range 39-79), had received a median of 3 prior lines of treatment (range 2-8). Grade 1 CRS was reported in 6/19 and Grade 2 CRS in 3/19. No ICANS was observed in the B-NHL and CLL cohorts. CAR engraftment was observed in 13/13 patients evaluated by qPCR with ongoing persistence in 12/13 patients at last follow-up. In the LG-NHL and DLBCL cohorts 10/10 and 4/5 evaluable patients respectively were in CMR by 18FDG PET-CT post-treatment. Responses were ongoing in 9/10 LG-NHL at 12 months and in 4/4 DLBCL at months 1, 3, 3 and 6. In the CLL cohort, 2/3 evaluable patients achieved MRD negative remission in the bone marrow with residual small volume lymph nodes by CT at 6 and 3 months of follow-up respectively. 1 CLL patient did not engraft and had SD at month 1. Summary/Conclusion: AUTO1 has a tolerable safety profile in patients with r/r B-NHL and CLL despite high disease burden. Early data shows excellent complete remission rates and excellent CAR engraftment/expansion. Additional patients, updated data and longer follow up will be presented.

Room of Knowledge (RoK): An initiative to encourage ad-hoc multi-disciplinary practical teaching

Objective: Clinical skill development is an essential part of speciality training in Obstetrics and Gynaecology. The COVID-19 pandemic has profoundly affected this with the move to remote learning, social distancing rules, increased workload, staff shortages and re-deployment. In order to improve access to clinical skills training it is imperative that we utilise the time spent in clinical settings such as labour ward and theatres to maximise training opportunities and skill development. Design: Qualitative study. Method: A pre-implementation online survey was carried out to analyse clinical skill training opportunities available to obstetric trainees and midwives on labour ward. In accordance with survey results, a trolley was assembled with the required equipment and easy to follow guides for carrying out several practical procedures and management of key emergency scenarios. The initial procedures and scenarios covered included;management of labour and delivery, post-partum haemorrhage, suturing and intrauterine device insertion. A log of the trolley's usage is being maintained and a follow up survey will be carried out in 3 months. Results: As per the initial survey, 90% of the respondents said that they were involved in ad hoc teaching only once a month or less. More than 80% trainees reported that they found impromptu teaching using models and aids on labour ward very useful and more than 95% said that they would attend such training if available. The most common procedures and/or skills identified as areas that should be covered included suturing, fetal scalp electrode attachment, breech vaginal birth and instrumental delivery. This project has significantly boosted the clinical teaching in our unit. The initial response from the log records revealed regular use on daily basis by trainee doctors as well as midwives. Operative vaginal delivery is the most utilised procedure to date. The first follow up survey will be conducted in April to assess the impact and analyse the scope for further expansion to include other aspects such as CTG training. Conclusion: The presence of the trolley along with materials and aids has helped create a learning environment on the labour ward with more frequent impromptu training even during busy shifts. It has instilled great enthusiasm amongst the trainees as well as trainers as evident from the verbal feedback and log records. A follow up survey and its statistical analysis will be carried out to substantiate our conclusion.

Effectiveness of Anti-IL4R Therapy Following Suboptimal Response to Anti-IL5/5R Therapy in Severe Eosinophilic Asthma

Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.

Prevalence of Postpartum Depression Following the COVID-19 Pandemic at an Urban Academic Institution

INTRODUCTION: Postpartum depression (PPD) is a complication of pregnancy commonly occurring within the first month of delivery. Numerous risk factors are associated with PPD, including financial stressors, inadequate emotional support, and perceived social isolation. This study evaluated the impact of the implemented social restrictions to mitigate the spread of the COVID-19 virus on the overall prevalence of PPD at an urban academic center. METHODS: Following institutional review board approval, a retrospective cohort study was performed of 1,097 subjects between 1 and 8 weeks postpartum. Group 1, the control group, included 420 women with routine PPD screening prior to the COVID-19 pandemic (April 1-December 31, 2019). Group 2, our case group, included 677 women with routine PPD screening during the pandemic (April 1-December 31, 2020). Both groups completed the Edinburgh Postnatal Depression Scale (EPDS), and the prevalence of PPD (defined as having an EPDS score greater than 11) was determined. Postpartum patients following fetal demise were excluded. RESULTS: The prevalence of PPD was higher in postpartum women before the COVID-19 pandemic (13.10%) when compared to postpartum women screened during the pandemic (10.78%). This increased prevalence, however, was not found to be statistically significant (P=.2474). CONCLUSION: Our study revealed no statistically significant difference in the prevalence of PPD before or during the COVID-19 pandemic. Nevertheless, the downward trend of PPD during the pandemic may be due to quarantine recommendations allowing families/spouses to work from home. The association of PPD and specific social support systems should be evaluated further.

'Into the Fire': A Focus Group Study of Redeployed Staff During the COVID-19 Pandemic

Background/aims: During the COVID-19 pandemic, redeployed staff whose services were temporarily suspended were offered a range of opportunities for work to support efforts to manage the impact of the pandemic. A new team known as the 'Cygnets' was established within an existing team to provide non-specialist end-of-life and bereavement care during the COVID-19 pandemic. 72 redeployed staff opted into this team. It is important to evaluate new services and one important component of this is understanding the perceptions of those staff who took on the new role. Objectives: To evaluate the service from the perspectives of staff Methods: Design: Focus group study Setting: One large, combined acute NHS Trust in Northern UK incorporating 4 hospitals Participants: A purposive sample of fourteen NHS staff who had worked as Cygnets during the COVID-19 pandemic Methods: Three focus groups. Transcribed and anonymised. Data analysed using Braun's approach to thematic data analysis. Results: Participants opted in to the role from a wide variety of clinical and non-clinical backgrounds, with great diversity in terms of prior experience of end of life care. Reasons for volunteering were both professional (for example, career development) and personal (for example, pre-existing anxiety around death and dying). Participants considered that overall, they had benefited on personal and professional levels from taking on the Cygnet role, and that this had been a learning experience in terms of knowledge, skills and attitudes. Challenges identified included those related to the broader emotional climate resulting from the rapidly intensified demand for end of life and bereavement support against a backdrop of restricted family visiting. Conclusions: This was a rapid response to a need for increased provision of compassionate end of life care and was a beneficial experience for staff. More research is required into the broader value of the non-specialist end of life care companion role within the hospital infrastructure.

Variability in test interval is linked to glycated haemoglobin (HbA1c) trajectory over time in people with diabetes

Introduction: Frequency of HbA1c testing links to outcome in terms of HbA1c control in diabetes. The influence of the variability of test-retest interval on HbA1c change needs to be determined. Methods: HbA1c results were collected from laboratory records on 3,872 people: HbA1c results at baseline and 5 years( ± 3 months) later with at least 6-tests during this period. We calculated the standard deviation (SD) of test interval for each individual. We then examined the link between deciles of SD of test interval/HbA1c level, stratified by baseline HbA1c. Results: In general, less variability in testing frequency = more consistent monitoring associated with better diabetes control over a 5-year period. This was most evident with moderately raised baseline HbA1c levels(54-75mmol/ mol[7.0-9.0%]). For example, in those with a starting HbA1c of 54-58mmol/ mol[7.0-7.5%], the lowest SDdecile associated with little change in HbA1c over 5 years, while for the highest SDdecile, HbA1c rose by 4-6mmol/ mol[0.4-0.6%], (p < 0.0001, standard beta 0.09-0.10). Multivariate analysis showed that the association was independent of age/sex/hospital site. Stratification by age suggested that the effect was most pronounced in those aged <65 years with baseline HbA1c 54-58mmol/ mol[7.0- 7.5%] (p < 0.0001, standard beta = 0.12). We also observed a 6.7-fold variation in the proportion of people in the top three SDdeciles across general practices. Conclusion/Interpretation: These findings indicate that consistency of testing interval, not just numbers of tests/year, is important in maintaining diabetes control, especially in those with moderately raised HbA1c. This suggests the need for developing systems to improve the regularity of HbA1c testing, especially given the recent impact of covid-19 on diabetes monitoring.

Family feedback in relation to adapting the parent and toddler cardiomyopathy coffee mornings to a virtual platform in response to COVID-19

Introduction: The Inherited Cardiac Conditions (ICC) clinical nurse specialist (CNS) team host coffee mornings for parents and their children who are affected by cardiomyopathy. These were held in response to parents' requests to meet other families affected by the condition. Support groups for families of children with heart disease can identify positive coping strategies and the need for psychological support (Jackson et al., 2018). Since the COVID-19 outbreak in the UK, incoming calls to the nurse specialists from families were greatly increased, due to heightened anxieties surrounding COVID-19 and its potential effects on children with cardiomyopathy. Therefore, the CNS team responded by adapting the coffee morning forum to a virtual platform with questions and answers surrounding COVID-19 and cardiomyopathy. Methods: The first virtual cardiomyopathy coffee morning was held on the 23rd June 2020 via Microsoft teams, a secure and accessible platform. Parents of children with cardiomyopathy under the age of 5 years were invited. Parents were asked to submit anonymous questions prior to the morning if they wished. It aimed to be more accessible for families, rebuild a support network and help ease anxieties surrounding COVID-19 in the presence of the consultant and the clinical nurse specialists. Results: 6 families attended. Feedback from parents was collated in relation to their experience of the first virtual coffee morning via email and feedback forms. This assisted in identifying the benefits of the event and how this can be adapted for future practice i.e. more regular sessions with guest speakers. Results identified that all parents found it very reassuring, informative and it eased their anxiety in relation to COVID-19 and cardiomyopathy. Conclusions: Overall, the adaptation of the coffee morning to a virtual platform was deemed valuable as evidenced by feedback from staff and families that attended. Although the coffee morning was focused around COVID-19 for the event that took place during the pandemic, the team envisage that the focus can change in accordance with participants wishes. The virtual coffee morning is an initiative that will be incorporated into the future practice of the CNS team to further support families with children affected by cardiomyopathy.

IMPROVING COMMUNICATION IN THE TIME OF COVID-19 - USING A DEDICATED COMMUNICATION SHEET

Background: A dedicated Communication Sheet was introduced on an Acute Frailty ward at the Royal Surrey County Hospital (by a Nurse-in-Charge and foundation doctors under the supervision of a Consultant Geriatrician) to improve communication between the Multidisciplinary team(MDT) and patients' NoK/families. Introduction: Communication with patients' NoK is an essential part of providing holistic care & has become important given the COVID-19 visiting restrictions. Multidisciplinary Team (MDT) members were facing difficulties in knowing the following while updating NoK: 1. The correct contact details of the Next of Kin and other significant persons involved in care. 2. When the last NoK update was done and what was discussed. 3. If the patient has consented to NoK updates. This led to dissatisfaction and complaints from families regarding the frequency and consistency of updates. To make this easier for staff, a communication sheet was introduced. Methods: A Plan-Do-Study-Act Method: was used. Following discussion at a ward governance meet, a survey was conducted to assess the difficulty faced by MDT members in NoK updates. A Communication Sheet designed by a Nurse-in-Charge and Foundation Doctors was trialled for 1 month. The sheet was updated following feedback. A repeat Survey was conducted to assess if NoK updates were easier after the intervention. Results: After the Introduction: of the Communication Sheets, the number of staff facing 'significant difficulty' in the above-mentioned parameters reduced and those facing 'no difficulty' increased. Feedback from MDT members suggested that they found the intervention useful. Conclusion: Dedicated communication sheets made updating families/NoK easier. This ensures consistent updates especially when visiting is restricted. This fosters a better patientclinician relationship. Given its success, we plan to share this with other frailty wards to scale up this intervention.

The Caribbean cruise industry and COVID-19: what planned strategic options exist for recovery for small island countries? (Special issue: What are the prospects for the post-pandemic Caribbean cruise industry?.)

Purpose: The aim of the paper is to examine the impacts of the coronavirus disease-2019 (COVID-19) pandemic on the Caribbean cruise industry and assess the post-pandemic prospects for recovery. Design/methodology/approach: The study used a qualitative approach applied through personal interviews as well as data from secondary sources. Findings: The prospects for the post-pandemic cruise industry reveal the need for long-term plans and strategies from Caribbean countries if the countries are to remain viable. Research limitations/implications: The research was limited to Jamaica, St. Lucia and Antigua and Barbuda. The scope could have been broadened to include other Caribbean islands such as Barbados. Practical implications: The study is practical and useful to tourism practitioners and governments seeking to create a balance between reaping the benefits of cruise tourism and safeguarding its citizens. Social implications: The pandemic has caused a re-examination of how people interact. Originality/value: The study adds to the body of literature on the post-pandemic survival of the Caribbean cruise industry and provides a useful briefing for practitioners.

Safety and Efficacy of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)

INTRODUCTION We have previously described AUTO1, a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR-T immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL. Cumulatively, this data confirms the intended function of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR-T therapy has been explored in indolent lymphomas such as follicular (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity including Grade 3-4 ICANS has been reported. We have initiated testing of AUTO1 in the setting of indolent and high-grade B-NHL and CLL (NCT02935257). METHODS Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised leukapheresate. Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m 2 x3) and cyclophosphamide (60mg/kg x1) prior to AUTO1 infusion, with the exception of the DLBCL cohort who additionally received a single dose of pembrolizumab (200mg) on day -1 to potentiate CAR-T expansion. AUTO1 dose varies based on the indication. Split dosing of 230 x10

Maximising Social Value and Health Impact – what is the role of PHIs?

Issue Public health Institutes (PHIs) need to build on traditional approaches to capture and measure their value and impact. As we transfer into the COVID-19 recovery phase, it is important to maximise the value of the health impact but also the social, economic and environmental impact of PHIs. Exploration is required to understand how the social value and impact of PHIs is, or can be, captured and measured. Existing research has illustrated the potential link between Health Impact Assessment (HIA) which assesses health and well-being through the lens of the determinants of health, and economic methods such as Social Return on Investment (SROI). This research aims to understand the current role which PHIs have, in order to strengthen advocacy for investment in public health and prevention in order to protect and improve population health. Description of the problem A scoping survey was designed and distributed digitally to national and regional PHIs via international networks. Semi-structured interviews were also used to add a qualitative value to the research to allow for triangulation of results. The survey data was analysed descriptively and interview data analysed thematically and coded. Results The results of the research present an understanding of the meaning of investment, social value and health impact within PHIs including how it is measured using SROI and HIA. It also highlights whether PHIs have considered how capturing social value and health impact can contribute to the recovery from COVID-19, and whether they believe that SROI and HIA have a role in achieving this. Lessons This innovative work aims to develop a picture of how PHIs are capturing and measuring the wider social, economic and environmental value of their programmes and services. Survey results will be used to help develop a framework for capturing the wider impact and value of public health at an international level, with an aim to achieving sustainable investment in future public health. Key messages Making the case for investing in public health by illustrating its social, economic and environmental value is vital. Understanding how to capture and measure the wider value of public health is imperative to aid the recovery from COVID-19.

The Health and wellbeing impacts of Home and agile working in Wales: A HIA Approach

The SARS-COV-02 pandemic has globally resulted in a number of policies and interventions to address and reduce the transmission of the disease throughout the population. Mitigation measures have ranged from ‘Staying at Home' or ‘Lockdowns' to social distancing policies and requirements to work from home when you can. Whilst there are a number of papers which discuss the effects of home or remote working on employees and their families the large scale shift, accelerated pace and wider impacts of such a shift has not been well explored in the literature or has been focussed on specific topics, for example, productivity. HIA is promoted as a beneficial tool to identify the wider impacts of a policy, plan or intervention across a population and as such is well placed to examine and articulate who in a population may be affected and how, and the inequalities that may be created by an intervention such as home working. Using the lens of social determinants and equity focussed-HIA, this work examines the wider impact of home working in Wales during the COVID-19 pandemic. It provides a coherent overview of the major impacts on health and the particular populations affected. It articulates the process followed, the key evidence based findings, discusses the gaps in the evidence base that require further exploration and the impact and influence it has had to date. Finally, it shares the transferable learning, which will be of use to researchers, policy and decision makers, organisations and public health agencies.

Does asthma control change when patients transition to home administration of mepolizumab?

Introduction: Mepolizumab is a biologic agent targeting interleukin (IL)-5 which is currently licensed as add-on therapy for severe eosinophilic asthmatic (SEA). It is usually administered in a hospital setting but with the option of homecare being introduced in 2019, the 4-weekly subcutaneous injections can be self-administered at home. We investigated whether there was a change in asthma control following the transition to home administration and whether a differential response to treatment exists following transition to homecare before and after the onset of the COVID-19 pandemic. Methods: Patients receiving mepolizumab via home care were stratified according to those who had a planned transition to homecare prior to 1st Feb 2020 versus those who had an unplanned transition after this date necessitated by the COVID-19 pandemic. The last Asthma Control Questionnaire-6 (ACQ6) measured in clinic ('baseline') was compared with that collected by telephone consultation 6-8 weeks after transition ('homecare'). Patients were excluded if both values were not available. Results: Of 87 mepolizumab patients included in the analysis, 46 were planned transitions. There was no significant (Figure presented) difference in the pre-biologic ACQ6 (p=0.07) between groups. Immediately prior to transition to homecare (baseline), the planned group had a lower mean ACQ6 than those in the unplanned group (1.19 vs 1.90, P=0.004). The ACQ6 on homecare decreased significantly in both groups (-0.47 in the planned group vs -0.56 in the unplanned group, both P<0.001). The ACQ6 for the planned cohort during homecare was significantly lower than that for the unplanned group (0.72 vs 1.34, P=0.012) (figure 1). (Table presented) Conclusions: We found a significant improvement in ACQ6 for all SEA patients established on Mepolizumab who transitioned to home mepolizumab administration. This improvement occurred irrespective of whether the transition was 'planned' or 'unplanned'. Further research is required to understand the potential influence of shielding during lockdown and the method of ACQ assessment (telephone vs face-to-face ACQ reporting in clinic) on this improvement.