Investigation into workplace ventilation at COVID-19 outbreak sites

Site visits were made to ten (non-healthcare) workplace COVID-19 outbreaks to assess ventilation. Measurements of carbon dioxide (CO2), temperature and humidity were made. Room activity and occupancy was observed, and ventilation management assessed. CO2 readings were used to identify areas of poor air quality, and where possible, airflow measurements were made at ventilation openings and CO2 decay rates were used to estimate ventilation rates. Poorly ventilated, regularly occupied spaces were frequently identified by this work. Measures to reduce transmission risk and improve ventilation included opening windows and reducing room capacities. Attempts at reconfiguration of mechanical ventilation systems were not common. Thermal comfort and heating costs were factors cited that influenced decision making. Overall understanding of ventilation was low and identified a need for simple tools to allow stakeholders to assess their workspaces. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Switching from intravenous to subcutaneous infliximab: Clinical and patient experience outcomes

Background: Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic. Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes. Method(s): The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch. Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8). Result(s): 31 patients consented to switch;F:M = 17:14. The majority of patients (16) had Crohn's disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24. At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score <5 or partial Mayo score <2), 96% had CRP <5 mg/Land 87% had FCP <250mug/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline. Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort. 15 patients submitted CUCQ-8 scores, of these 7 patients' scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline. Conclusion(s): Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.

An Assessment Of A Guided Self-Help and Patient Initiated Review Pathway for Ulcerative Proctitis

Background: The COVID-19 pandemic has placed great strain on standard outpatient services including those with IBD. There has been interest in using guided self-management and patient-initiated review to allow patients to manage their condition, while at the same time reserving outpatient capacity for those needing seen urgently. We developed a pathway for patients with stable ulcerative proctitis, which included a leaflet on symptom managment and when to contact the IBD nurses if ongoing symptoms. Method(s): Patients were identified from clinic lists cancelled during the pandemic who had a diagnosis of ulcerative proctitis. Case notes were reviewed to ensure a correct diagnosis and inclusion criteria met(stable disease, no immunosuppressant treatment). These patients were sent a Guided Self-Management leaflet in the post. A follow on questionnaire was sent 6 months after ensuring patients were happy with the information received. Non-responders were sent a second questionnaire and/or telephone call. Result(s): 37 Patients were identified. We received responses (via post, phone or email) from 28/37 patients (76%). 10/28 (36%) didn't receive or do not recall receiving the leaflet. 18/28 (64%) received the leaflet. Of those who received the leaflet, 16/18 felt it was easy to understand and contained enough information to confidently manage their symptoms. 2 patients had 1 flare and 3 patients had multiple flares after receiving the leaflet. Of those with flares, 2 patients were able to self-manage their proctitis using the guided self help information. 2 patients had to contact the IBD nurses. These patients were called back within 24 hours and received useful advice. One patient had forgotten to use the leaflet. No one required rescue steroids or admission to hospital. Overall, 17/18 (94%) felt the service was good or excellent compared to previous clinic review systems. Conclusion(s): These results suggest patients are receptive to using guided self-management and patient-initiated review. Although we were not expecting to see many flares, given the low risk selected group, the results suggest patients can successfully manage flares and contact our services for support if required. It is a concern a significant proportion of patients did not recall receiving the leaflet. Although this is a small subgroup, the results show clinic time can be saved which remains a pressurised resource as we recover from the pandemic. The principles of guided self management and patient initiated review could be applied to other patient groups(eg stable UC patients not on immunosuppressants). In future it would be important to ensure patients receive and understand the leaflet. A clinic appointment prior to discharge into such pathways should be considered.

The changing role of pre-admission work experience (clinical visits) in Therapeutic Radiography, Diagnostic Radiography and Operating Department Practice: Student perspectives (Part 1).

INTRODUCTION: Clinical visits (work experience opportunities) are a recommended part of admissions processes for many diagnostic and therapeutic radiography courses but not for operating department practice (ODP) where observational visits are challenging for applicants to obtain. The Covid-19 pandemic interrupted access to visits for all prospective students; this study presents a review of the value of clinical visits and alternatives. METHODS: This article reports the initial qualitative phase of a three-phase mixed methods study. Using a critical realist approach, focus groups explored first year student experiences of the 'ideal' pre-admission clinical visit and alternative resources. A structured review of Online Prospectus (OLP) entries was undertaken by two student researchers to ascertain the requirements for clinical visits for the three professions. RESULTS: Four focus groups included 25 first year students interviewed prior to their first clinical placement (14 therapeutic radiography, 5 diagnostic radiography and 6 ODP students). Three themes were constructed, namely: informing career choices, the clinical visit experience, and the value of clinical visits. Clinical visits affirmed rather than inspired career choices. The best timing for a visit was before admission interviews and optimal duration was a full day. Interacting with current students was the most valued aspect. Videos and simulations provided in-depth information about the professional role and allowed replay, but some participants found the videos uninspiring. OLP entries present a confusing picture for applicants who may be researching several Universities and professions. CONCLUSION: Clinical visits were deemed 'vital' to radiography student career choices, yet ODPs who could not access visits were comfortable with videos. Simulated visits are a safe option amidst the pandemic but must capture the dynamic and patient-centred nature of practice to accurately inform career choices.

A REVIEW OF GUIDED SELF MANAGEMENT FOR PATIENTS WITH ULCERATIVE PROCTITIS

Introduction With secondary care services transitioning into virtual and telephone consultations our aim was to minimise face to face routine appointments during the Covid 19 pandemic for patients with stable ulcerative proctitis. We assessed patient satisfaction of the guided self-management leaflet and whether this can be adopted long term for this patient group. Methods From our IBD database we identified all patients with a coded diagnosis of 'proctitis'. Clinical portal notes and previous colonoscopies were reviewed to ensure correct diagnosis. Only patients with stable disease - minimal contact with IBD nurses, no recent admissions, infrequent flares were included. Identified patients were sent a Guided Self-Management leaflet in the post and a follow-on response questionnaire was sent around 6 months later. For non-responders a second questionnaire and/or telephone was arranged. Results 37 Patients were identified. We received responses (via post, phone or email) from 28/37 patients (76%). 10/28 (36%) didn't receive or do not recall receiving the leaflet.18/ 28 received the leaflet (64%). of those who received the leaflet, 16/18 felt it was easy to understand and contained enough information to confidently manage their symptoms. 2 patients had 1 flare and 3 patients had more than 3 flares since receiving the leaflet. of those with flares 2 patients were able to self-manage their proctitis using the leaflet provided. 2 patients had to contact the IBD nurses. These patients were called back within 24 hours and received useful advice. One patient had forgotten to use the leaflet. No one required rescue steroids or admission to hospital. Overall, 17/18 (94%) felt the service was good or excellent compared to previous clinic review systems. Conculsions The above results suggest the Self Guided Management Leaflets in this low symptom burden proctitis group are safe and easy to use. Overall feedback of the leaflet was positive and allowed the vast majority of patients to selfmanage their symptoms without the input of the IBD nurses. The main limitations of this study were leaflet distribution and questionnaire response. Issues included: wrong patient address, the leaflet being thrown away and patients forgetting to use it during a flare. We therefore suggest all patients identified have a Face-to-Face appointment at point of diagnosis or subsequently with an IBD nurse to issue and discuss leaflet. This will ensure each patient receives the leaflet and hopefully improve engagement with self-managing flares. We plan to repeat the survey in 6-12 months with a larger patient group.

COVID-19 HISTORY REPORTED BY MEN WHO HAVE SEX WITH MEN (MSM) IN THE UK IN A LARGE, COMMUNITY SURVEY ('RIISH-COVID')

Introduction As COVID-19 has deepened health inequalities, we examine the COVID-19 experience of MSM as a population disproportionately affected by poor-health. Methods An online cross-sectional survey of MSM recruited via social media and dating applications for 3 weeks in November/December 2021. Questions included those on COVID-19 experience addressing: COVID-19 test history;when (if ever) tested positive;self-perception of ever having had COVID-19 and long-COVID. Logistic regression was used to assess sociodemographic and behavioural characteristics associated with these outcomes. Results Among 1,038 participants (median age: 41;88.1% white ethnicity): most reported ever testing for COVID-19 (95.0%;n=987), while 19.6% (193/987) reported a positive result [8.1% (80/987) testing positive since August 2021]. In those without a prior positive test (n=793) or testing history (n=52), an additional 148 participants reported self-perceived COVID, resulting in 32.8% (341/1038) with a COVID-19 history. In these, one-quarter (25.2%;86/341) reported long- COVID (8.3%;86/1038 of all) and 4.1% (14/341) hospitalisation history for COVID-related symptoms (1.8%;19/1038 of all). COVID-19 history was associated with residence in England (aOR:1.52,95%CI:1.02-2.28), degree-level education (aOR:1.33;95%CI:1.01-1.75), and vaccination status (aOR:2.98,95%CI:1.61-5.53, none/one dose vs. boosted). Long-COVID was associated with hospitalisation history (aOR:3.21;95%CI:1.09-9.45) and degree-level education (aOR:0.56;95%CI:0.36-0.99). Conclusion In this large community sample, one in five MSM reported testing positive for COVID-19, and one-third had a COVID-19 history. There was no evidence of age or ethnicityrelated inequalities, although long-COVID appears to exceed general population estimates. Continued monitoring of long- COVID in MSM is warranted as COVID-19 infections in the UK continue to increase.

DIFFICULTY ACCESSING CONDOMS BECAUSE OF THE COVID-19 PANDEMIC REPORTED BY MEN WHO HAVE SEX WITH MEN (MSM) IN THE UK IN A LARGE, COMMUNITY-BASED CROSS-SECTIONAL SURVEY ('RIISHCOVID')

Introduction COVID-19 restrictions severely impacted in-person sexual health services, an important access point for condoms. We examine whether MSM in the UK had difficulty accessing condoms because of COVID-19 restrictions and associated factors. Methods Data on difficulty accessing condoms since the start of the pandemic (23rd March 2020) were collected as part of a short, online cross-sectional survey of MSM in November/ December 2021, recruited via social media and Grindr. Eligible participants were UK-resident MSM (cis/trans/non-binary person assigned male at birth - AMAB), aged ≥16 years who were sexually active (reported sex with men in the last year). Multivariable logistic regression to adjust for age and numbers of new sex partners was used to examine if and how reporting this outcome varied by key sociodemographic factors. Results Of all participants (N=1039), over 1 in 7 (13.3%;n=138) reported ever having difficulty accessing condoms, of whom, over half (55.8%;n=77) reported difficulty due to the pandemic (7.4% of all participants). Reporting difficulty accessing condoms was significantly higher among: Younger MSM (aged 16-29 years vs. ≥45;12.8% vs. 4.9%;aOR=2.78);trans/non-binary AMAB participants (vs. cisgender males;24.4% vs. 6.6%;aOR=4.86);bisexually-identifying MSM (vs. gay-identifying;11.1% vs. 6.5%;aOR=1.78);and MSM without degree level education (vs. having a degree;9.8% vs. 5.6%;aOR=2.01). Discussion A minority of sexually active MSM reported difficulty accessing condoms because of the pandemic, however, this was more common among those who already experience a disproportionate burden of poor sexual health. Interventions are needed to address these inequalities in accessing this important primary STI/HIV prevention measure. (Table Presented).

COVID-19 VACCINATION UPTAKE AND COVERAGE REPORTED BY MEN WHO HAVE SEX WITH MEN (MSM) IN THE UK IN A LARGE, COMMUNITY SURVEY ('RIISHCOVID')

Introduction MSM are disproportionately affected by health inequalities which may be exacerbated by COVID-19 and pandemic- related restrictions. We examine uptake of the COVID- 19 vaccine in MSM and assess factors associated with vaccination status. Methods An online cross-sectional survey of MSM recruited via social media and dating applications for 3 weeks in November/December 2021. Questions included those on vaccine offer and uptake (1 dose/2 doses/2 doses+booster). Logistic regression assessed factors associated with reporting full vaccination status (≥2 doses) by sociodemographic characteristics, HIV status, self-reported COVID history, and mental health indicators. Results Of 1,039 participants, 98.2% (n=1,020) reported everhaving been offered a COVID vaccine, of which 98.0% (1,000/1,020) reported ≥1 dose and 96.5% (985/1020) full vaccination status. In multivariate models, full vaccination status was associated with: age (aOR:1.04, 95%CI:1.01-1.06 per increasing year), gender (aOR: 0.26, 95%CI:0.09-0.72, gender minority vs cis male), degree-level education (aOR: 2.11,95% CI:1.12-3.98), employment since lockdown (aOR: 2.07,95% CI:1.08-3.94), single relationship status (aOR: 0.50,95% CI:0.25-1.00), self-reported COVID-19 history (aOR: 0.47, 95%CI:0.25-0.88), HPV vaccination history (aOR: 3.32, 95% CI:1.43-7.75), and self-reported low life-worth (aOR: 0.29, 95%CI:0.15-0.54). Conclusion This large community survey suggests COVID-19 vaccine uptake and coverage is high in MSM and exceeds general population vaccination estimates. However, inequalities appear to exist in some groups, including younger age-groups, gender minorities, and those with poorer mental health less likely to report full vaccination. Efforts are needed to limit COVID-related exacerbation of health inequalities in these groups who already experience a greater burden of poor health relative to other MSM.

SEXUAL BEHAVIOUR, STI AND HIV TESTING AND TESTING NEED AMONG MEN WHO HAVE SEX WITH MEN (MSM) PRE- AND POST-COVID-19 RESTRICTIONS IN THE UK

Introduction We examine changes in sexual behaviour, STI & HIV testing and testing need among MSM in the UK preand post-COVID-19 restrictions. Methods An online survey of 1,309 MSM recruited via social media and Grindr over three weeks in November/December 2021. Questions on sexual behaviour and service use had an approximate three-month lookback period corresponding to a period of no/limited COVID-19 restrictions. Unmet testing need was defined as reporting any new and/or multiple condomless anal sex (CAS) partners without a recent STI/HIV test. MSM recruited through Grindr who were UK-resident, cisgender, aged ≥16 years who reported sex with men in the last year (N=430) were compared to those from a related 2017 survey (N=1914) using multivariable regression to adjust for demographic differences between the samples. Results Compared to the 2017 survey, sexual risk behaviour was higher in the 2021 survey: ≥1 recent new sex partner (71.5% vs. 81.5%, respectively, aOR=1.80);≥2 recent CAS partners (30.1% vs. 48.8%, aOR=2.23). Reporting recent testing for STIs/HIV was also higher in late 2021 (37.3% vs. 42.6%, aOR=1.34;and 48.7% vs. 45.1%, aOR=1.27, respectively). However, there was no significant change in the proportion with unmet need for STIs (41.4% vs. 44.2%) and HIV (34.8% vs. 39.3%). Discussion These large, community surveys of MSM in the UK suggest greater sexual risk behaviour post-restrictions in 2021 compared to 2017. However, while we found no evidence of reduced service accessibility following the removal of most restrictions, there remains considerable unmet STI/HIV testing need among UK MSM. (Table Presented).

Dose-Dependent Respiratory Viral Inhibition by a Safe Inhaled Alkaline Treatment

Introduction: SARS-CoV-2 respiratory infection is pandemic and continues to cause significant mortality and morbidity worldwide. Respiratory viral infections in general are a leading cause of hospital admissions and mortality throughout the world as well. Most respiratory viral infections require an acidic intracellular and endosomal environment in order to enter host cells, replicate, and cause illness. We study the beneficial effects of airway alkalinization by an inhaled drug, Optate, that we currently have demonstrated is safe to inhale by healthy subjects and those with stable airways disease. We have recently shown that treatment with 4.5 mg/ml Optate safely inhibits SARS-CoV-2 infection in primary human airway epithelial cells (HAECs). We hypothesized that this inhibition would be dose dependent and that Optate would also inhibit other viral infections in a dosedependent manner. Methods: HAECs were infected with respiratory syncytial virus with green fluorescent protein (RSV-GFP) or SARS-CoV-2 virus. A dose-response curve of Optate was performed in each infection model and compared to a control group. Viral infection was quantified using fluorescence microscopy, plaque assays, and viral protein quantification. Optate pH was measured at each dose and a corresponding dose/pH curve was calculated to compare pH to dose-response. Results: SARS-CoV-2 infection was significantly inhibited by doses of Optate > 2.25 mg/ml, corresponding with an Optate pH > 9.2 (n = 4, p < 0.001). RSV infection was significantly inhibited by doses of Optate > 2 mg/ml, corresponding with an Optate pH > 9 (n = 3, p < 0.001). No significant difference was noted between control and Optate treated HAECs at lower concentrations of Optate. Conclusions: Optate inhibits SARS-CoV-2 and RSV viral infections in a dose-dependent manner that correlates with Optate pH. These findings suggest that Optate may be an inhaled therapeutic for patients with respiratory viral infections. (Table Presented).

IN PURSUIT of MEANINGFUL INSIGHT;COVID REMOTE COLLABORATION and DESIGN AS PROVOCATION

Conducted from June 2020 until the time of writing, this design research activity was conducted as part of the 3 year, H2020, Pan European TInnGO project which aims to create a sustainable paradigm shift in gender and diversity mainstreaming in transport. Such a shift is needed due to the lack of sex disaggregated gender data, gender gaps in employment and decision making and women in STE(A)M able to rise to leadership positions. This lack of diversity at all levels of transport, together with difficulties in engaging ‘hard to reach groups’ in transport planning, means that transport services and innovation continue to fail to consider gender and diversity. This would also encourage design input into future transport. A central concept of TInnGO was to use design activities as provocations and ways to engage with people in new ways – e.g., through visualizations, vignettes and cocreation activities – to develop greater insights into mobility problems and drive gender and diversity sensitive smart mobility solutions. Led by Coventry University, it was anticipated that this would entail management and leadership of codesign sessions in 10 Pan-European hubs. The Covid-19 pandemic significantly disrupted plans, making travel, physical co-design and contact with vulnerable groups impossible. The paper discusses strategies developed to work with placement students to develop gender and diversity sensitive smart mobility design provocations based on information provided by national hubs, and the technological challenges computer supported cooperative design posed. © PDE 2021.

Venetoclax with Azacitidine or Low Dose Cytarabine As an Alternative to Intensive Chemotherapy in Fit Adults during the COVID19 Pandemic: Real World Data from the UK National Health Service

Background Based on early evidence of a high rate of coronavirus mortality in patients with acute myeloid leukaemia (AML) undergoing intensive chemotherapy (IC), the national health service (NHS) in the United Kingdom temporarily made venetoclax available as an alternative therapy, with the aim of reducing both mortality and healthcare resource use. From late April 2020, venetoclax was available to patients aged >16y with NPM1 mutation without FLT3 internal tandem duplication (ITD), patients aged >50y with NPM1, IDH1 or IDH2 mutations (regardless of FLT3 status) and patients aged >60y without favourable-risk cytogenetics. Venetoclax could be given with either azacitidine or low-dose cytarabine (LDAC), with the latter recommended mainly for patients with NPM1 mutation. We report a health-system-wide real world data collection for toxicity and patient outcomes across 65 NHS Hospitals. Methods Each patient was registered on a central NHS database. Clinicians certified that their patient met the above criteria, had not received previous AML treatment, and was fit for induction chemotherapy. Anonymised data were retrospectively collected by treating physicians. Venetoclax dose, duration and toxicity information was requested for the first 4 cycles of therapy. Response definitions were as per European Leukaemia Network (ELN) guidelines. A total of 870 patients have been registered on the scheme, with outcomes reported here for those with follow-up information at a data cut on 1st August 2021. Results There were 301 patients, median age 72y (range 34 - 90) with 62% male. The majority (81%) had an ECOG performance status of 0-1. AML was secondary to a previous haematological disorder in 33%, therapy-related in 10% and de novo in the remaining 57%. MRC cytogenetic risk was intermediate in 70% and adverse in 27%. NPM1 mutations were detected in 28% and FLT3-ITD in 12%. Next-generation sequencing results were available in 86% of patients, which detected mutations in IDH1 or IDH2 in 28%, ASXL1 in 20%, RUNX1 in 17% and TP53 in 12%. The ELN risk was favourable for 23%, intermediate for 30% and adverse for 44%. A majority received venetoclax in combination with azacitidine (85%), with the remaining 15% receiving LDAC. The LDAC cohort was enriched for de novo AML (76% vs 54%) and NPM1-mutated disease (56% vs 23%). Most patients (81%) followed the recommended initial schedule of venetoclax 100mg daily for 28 days in combination with posaconazole or voriconazole. Patients spent a median 14 days in hospital in cycle 1, then a median of 0 days for cycles 2-4. In cycles 1, 2, 3 and 4, the median number of days for recovery of neutrophils to >0.5x10 9/L was 33, 25, 24 and 14 respectively, and the median number of days to recovery of platelets to >50x10 9/L was 22, 3, 0 (no drop below 50) and 0. The composite complete remission (CR) / CR with incomplete haematological recovery (CRi) rate was 70%. MRD data is being collected. The best response was morphological leukaemia free state (MLFS) in 2%, partial remission in 7% and refractory disease in 11%. CR/CRi was higher in de novo (78%) compared to secondary AML (57%, p=0.02);NPM1 mutated (78% vs 67%, p=0.02) and IDH1/IDH2 mutated disease (85% vs 62%, p=0.02). ELN favourable risk patients had the highest CR/CRi rate (85%, intermediate 71%, adverse 60%, p=0.01). Median follow-up was 8.2 months (95%CI 7.8 - 9.0) with median overall survival (OS) 12.8 months (95%CI 10.9 - not reached). Mortality at day 30 was 5.7% and day 60 was 8.4%. 12-month overall survival was 51%, increasing to 71% in those who achieved CR/CRi. Survival was poorer in secondary (HR 1.9, p <0.01) and therapy-related AML (HR 2.1, p=0.02), better in NPM1 mutated (HR 0.6, p=0.02) and IDH mutated (HR 0.5, p=0.02) disease and poorer with TP53 mutation (HR 2.0, p=0.01). Overall survival did not differ for patients treated with LDAC compared to azacitidine (HR 1.1, p=0.7). Conclusion This large real-world study demonstrates CR/CRi and survival rates comparable to those reported in prospective clinical trials. Importantly, during t e COVID-19 pandemic, the adoption of venetoclax regimens permitted the great majority of treatment to be delivered as an outpatient with significant resource saving at a time of critically constrained inpatient resources. The data support prospective comparisons of venetoclax-based regimens to IC in fit adults with AML particularly in older patients with de novo AML, NPM1-mutated and IDH-mutated disease. [Formula presented] Disclosures: Belsham: Celgene: Other: meeting attendance;Abbvie: Other: meeting attendance. Khan: Abbvie: Honoraria;Astellas: Honoraria;Takeda: Honoraria;Jazz: Honoraria;Gilead: Honoraria;Novartis: Honoraria. Khwaja: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Latif: Kite: Consultancy, Honoraria, Speakers Bureau;Jazz: Consultancy, Honoraria;Daiichi Sankyo: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astellas: Consultancy, Honoraria, Speakers Bureau;Takeda UK: Speakers Bureau. Loke: Pfizer: Honoraria;Amgen: Honoraria;Janssen: Honoraria;Novartis: Other: Travel;Daichi Sankyo: Other: Travel. Murthy: Abbvie: Other: support to attend educational conferences. Smith: ARIAD: Honoraria;Pfizer: Speakers Bureau;Daiichi Sankyo: Speakers Bureau. Whitmill: Daiichi-sankyo: Other: travel fees;EHA in stockholm: Other: conference support. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dillon: Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Jazz: Other: Education events;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events;Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau;Menarini: Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Other: Educational Events, Speakers Bureau;Amgen: Other: Research support (paid to institution);Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events.

Gilteritinib for Relapsed Acute Myeloid Leukaemia with FLT3 Mutation during the COVID-19 Pandemic: Real World Experience from the UK National Health Service

Background Early data suggest that patients undergoing salvage chemotherapy for relapsed or refractory (R/R) acute myeloid leukaemia (AML) have poor outcomes if infected with SARS-CoV-2, and nosocomial transmission has been a major problem worldwide. Gilteritinib is effective in R/R FLT3 mutated AML, is significantly less immunosuppressive and does not require hospital admission, however at the start of the pandemic this was not yet approved for routine use in all countries. In the United Kingdom, the National Health Service (NHS) made gilteritinib available as an emergency measure from late April 2020 to patients aged >16y with R/R FLT3 mutated AML, with the aim of reducing both mortality and healthcare resource use. We report a health-system-wide real world data collection for toxicity and patient outcomes across 27 NHS Hospitals. Methods Each patient was registered on a central NHS database, with clinicians certifying that their patient met the above criteria. Anonymised data were retrospectively collected by treating physicians. Gilteritinib dose, duration and toxicity information was requested for the first 4 cycles of therapy. Response definitions were as per European Leukaemia Network (ELN) guidelines. A total of 81 patients have been registered on the scheme, with outcomes reported here for those with follow-up information at a data cut on 1st August 2021. Results Fifty patients were included with a median age of 59y (range 19 - 77) and 50% male. The majority (83%) had an ECOG performance status of 0-1. AML was secondary to a previous haematological disorder in 12%, therapy-related in 4% and de novo in the remaining 84%. The disease was refractory to the last therapy in 38%. Most patients had previously received 1 (65%) or 2 (33%) lines of therapy, including intensive chemotherapy in a majority (86%). A FLT3 inhibitor had previously been administered to 45% and 35% were post allogeneic transplant. The FLT3 mutation was an internal tandem duplication (ITD) in 80% and tyrosine kinase domain (TKD) mutation in 22%. NPM1 mutations were detected in 34%. Next-generation sequencing results were available for 94% of patients, with mutations in IDH1 or IDH2 in 12.5%, ASXL1 in 2%, RUNX1 in 21% and no TP53 mutations. Patients spent a median 3.5 days in hospital in cycle 1, 0 days in cycles 2 and 3 and 1 day in cycle 4. In cycles 1, 2, 3 and 4, the median number of days of grade 4 neutropenia was 18, 7, 7.5, and 6.5 respectively, and the grade 4 thrombocytopenia was 2, 7, 0.5 and 0.5. The composite complete remission (CR) / CR with incomplete haematological recovery (CRi) rate was 27%. MRD data is being collected. The best response was morphological leukaemia free state (MLFS) in 4%, partial remission (PR) in 25% and refractory disease in 38%. The rate of combined CR/CRi did not differ in those with previous exposure to FLT3 inhibitors (23% vs 32%, p=0.6) or with past allogeneic transplant (29% vs 27%, p=0.3). There were no CR/CRi in patients with adverse cytogenetic risk. Median follow-up was 10.5 months (95%CI 7.3 - 12.3) with median overall survival (OS) 6.7 months (95%CI 4.5 - not reached). Mortality at day 30 was 0% and day 60 was 14%. 12-month overall survival was 38%. Patients who achieved a CR/CRi had a 12-month OS of 83%, and for PR this was 35%. Survival did not differ in those with previous FLT3 inhibitor exposure (HR 1.0, p>0.9) or allogeneic transplant (HR 0.63, p=0.3). Seven patients (14%) so far have been bridged with gilteritinib to allogeneic transplant. Conclusion Our data demonstrate that gilteritinib is well tolerated and clinically active in adults with relapsed FLT3 mutated AML. Importantly, during the COVID-19 pandemic, its availability has permitted the great majority of treatment to be delivered as an outpatient with significant resource saving at a time of critically constrained inpatient resources. Patients who achieve CR/CRi have good short-term outcomes and are able to proceed to a potentially curative allogeneic stem cell transplant. [Formula presented] Disclosures: Belsham: Celgene: Other: meeting attendance;Abbvie: Other: meeting attendance. Byrne: Incyte: Honoraria. Khan: Abbvie: Honoraria;Astellas: Honoraria;Takeda: Honoraria;Jazz: Honoraria;Gilead: Honoraria;Novartis: Honoraria. Khwaja: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Latif: Kite: Consultancy, Honoraria, Speakers Bureau;Jazz: Consultancy, Honoraria;Daiichi Sankyo: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astellas: Consultancy, Honoraria, Speakers Bureau;Takeda UK: Speakers Bureau. Loke: Amgen: Honoraria;Daichi Sankyo: Other: Travel Support;Janssen: Honoraria;Novartis: Other: Travel Support;Pfizer: Honoraria. Munisamy: Jazz Pharmaceuticals: Speakers Bureau;Roche: Speakers Bureau. Murthy: Abbvie: Other: support to attend educational conferences. Smith: Daiichi Sankyo: Speakers Bureau;Pfizer: Speakers Bureau;ARIAD: Honoraria. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dillon: Amgen: Other: Research support (paid to institution);Astellas: Consultancy, Other: Educational Events, Speakers Bureau;Menarini: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events;Jazz: Other: Education events;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events.

Low Frequency of T Cell and Antibody Responses to Vaccination Against Sars-Cov-2 in Patients Post Allogeneic Stem Cell Transplantation in Comparison with Chronic Myeloid Malignancy Patients

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented healthcare challenges on a global scale. Impressive efforts have led to rapid development of multiple efficacious vaccines against SARS-CoV-2, however concerns remain over the degree of protection vaccination offers to immunocompromised recipients. To answer this question, we have designed a prospective study to evaluate response to vaccination in patients with haematological malignancies (Harrington, Leukaemia 2021;Harrington, BJHaem, 2021). 103 patients were included with samples collected in 60 patients after first dose and 71 patients following second dose. We have analysed humoral and T cell response to a first dose of vaccine against SARS-CoV-2 in patients post allogeneic stem cell transplantation (HSCT) and compared those to patients with CML or MPN. Methods: ELISA plates were coated with antigen Nuclear (N) protein or the S protein. Serial dilutions of plasma were added to wells and incubated for 2 h at room temperature. Control reagents included N-specific monoclonal antibody, S-specific monoclonal antibody, negative control plasma, positive control plasma and blank wells. Secondary antibody was added and incubated for 1h at room temperature. IgG was detected using goat-anti-human-Fc-AP and plates read at 405 nm. Where an EC50 was not reached at 1:25, a plasma was considered seropositive if the OD at 405nm was 4-fold above background and a value of 25 was assigned. T cell functionality was assessed using intracellular cytokine staining after incubation with SARS-CoV-2 specific peptides covering immunogenic domains of the Spike (S) protein. A response was considered positive if there was a 3-fold increase in pro-inflammatory cytokine expression from baseline, and above a threshold of 0.01. Specific peptides (0.25 µg/ml), anti-CD28 and BFA were added to cells. Unstimulated cells were utilised as negative controls. Cells were stained with viability dye, then with antibodies directed against surface markers, and fixed and permeabilised prior to staining for intracellular cytokines TNFa and IFNg. Gating on lymphocytes, single cells, live cells, CD3+ cells, CD4+ cells and CD4- (CD8+) was performed. Results: Of the 103 patients included in this study, post vaccination evaluation on 56 patients have been analysed so far, including 37 patients with chronic myeloid malignancies (MPN n=21 and CML n=16) and 19 patients post HSCT. From the latter group, median time since transplant was 53.9 months (18.7 to 76.8) with 12 participants on extracorporeal photopheresis (ECP) therapy for graft versus host disease (GvHD) with median frequency of 24.5 days (14-42). BNT162b2 vaccine was administered to 48 patients (85.7%). An anti-S IgG response was observed after a first dose in 16/21 (76.1%) of the MPN group and 14/16 (87.5%) of CML patients, but in only 7/19 (36.8%) of post HSCT patients (Fishers Exact Test - p=0.02/0.002, Fig 1a). Of the latter group a low positive value where an EC50 was not reached was observed in 4/19 (21.1%) and a moderate response in 3/19 patients (15.8%). Of the 12 patients with active GvHD on ECP, a positive response was observed in 4 patients (33.3%), however only one patient recorded a response where an EC50 was measurable. A T cell response was observed in 16/20 (80%) of the MPN group and 14/15 (93.3%) of those with CML after a single dose, with a polyfunctional T cell response (>1 cytokine) observed in 65% and 80% respectively. In comparison only 5/19 patients (38.5%) post HSCT mounted a T cell response (p=0.027/p=0.002, Fig 1b), with a CD4+ response in 4 (30.8%) and a CD8+ response in 3 (23.1%). In this group, a polyfunctional T cell response was found in 4/19 patients (30.8%). 33.3% of patients with GVHD requiring ECP had a T cell response, compared with 42.9% in post HSCT without GVHD. Summary: Despite encouraging results of antibody and T cell response to a first vaccination dose in patients with chronic myeloid malignancies, these results raise concerns regarding the humoral and T cell respo ses to vaccination in patients post HSCT, recognised as a particularly immunosuppressed group. Further longitudinal data is required to determine if these results translate into a reduction in cases and severity of infection in these groups. We are currently analysing the response to a second vaccine injection and responses to sequential doses of vaccination across the whole cohort will be presented. [Formula presented] Disclosures: Harrington: Bristol Myers Squibb: Research Funding;Incyte: Honoraria. Radia: Blueprint Medicines Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Study steering group member, Research Funding;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Education events;Cogent Biosciences Incorporated: Other: Study Steering Committee;EXPLORER and PATHFINDER studies: Other: Member of the Response Adjudication Committee. Kordasti: Beckman Coulter: Honoraria;Celgene: Research Funding;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Alexion: Honoraria. Dillon: Menarini: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau;Astellas: Consultancy, Other: Educational Events, Speakers Bureau;Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events;Amgen: Other: Research support (paid to institution);Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events;Jazz: Other: Education events;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees. Harrison: Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Incyte Corporation: Speakers Bureau;Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Constellation Pharmaceuticals: Research Funding;Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Sierra Oncology: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. de Lavallade: Bristol Myers Squibb: Research Funding;Incyte: Honoraria, Research Funding;Novartis: Speakers Bureau.

Examining the impact of the uk's COVID-19 public health response on sexual behaviour and health service use among msm

Background The introduction of social distancing in response to the COVID-19 pandemic led to reduced STI/HIV service provision in the UK. We investigated sexual risk behaviours among MSM and unmet need for sexual healthcare during the pandemic. Methods A cross-sectional online survey (N=2,018) fielded via social media and dating apps (23/06-14/07/2020). We examined sexual behaviour and service use since lockdown (23/03/ 2020) and in the three previous months, and 'unmet need for STI testing' since lockdown (any new male partners and/or multiple condomless anal sex (CAS) partners without testing for STIs). We compared behaviours over the past three months between socio-demographically equivalent sub-samples recruited via Grindr into the present survey (N=956) and a 2017 survey (N=1,918). Results In 2020, 36.7% of participants reported new male partners and 17.3% reported multiple CAS partners since lockdown. Comparing time since lockdown vs previous three months, HIV testers were less likely to test at sexual health clinics (22.3% vs 70.2%) and more likely to use free online self-sampling services (64.3% vs 17.1%), and PrEP users were less likely to report PrEP use (21.7% vs 65.7%). Since lockdown, 25.3% of participants had unmet need for STI testing. Unmet need was more likely among Asian vs White participants (aOR=1.76,[1.14-2.72],p=.01);living in Scotland (aOR=2.02,[1.40-2.91],p<.001) or Northern Ireland (aOR=1.93,[1.02-3.63],p=.04) vs England;and living with HIV (aOR=1.83,[1.32-2.53],p<.001). Compared to 2017, the 2020 sub-sample were less likely to report new male partners (46.8% vs 71.1%, p<.001), multiple CAS partners (20.3% vs 30.8%, p<.001) and unmet need (32.8% vs 42.5%, p<.001) in the past three months. Conclusion We found ongoing potential STI/HIV transmission among MSM during the initial UK lockdown, despite a reduction in sexual activity, and potential inequalities in access to sexual healthcare. These findings will support public health planning to mitigate against health risks during and after the COVID-19 response..