Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

A Rapid Evaluation of Virtual Grief Cafes across Two National Public Health Organisations

Introduction Restrictions during the COVID-19 pandemic adversely impacted bereavement as: visiting the dying, funerals, family meetings, access to bereavement services were disrupted. Pandemic work at Public Health England and Test and Trace was unrelenting. Enforced home working enhanced isolation. Many colleagues experienced difficult bereavements with little access to normal support networks. Aims To further understand how a workplace grassroots virtual grief cafe can support the bereaved. Methods A grassroots group of bereaved staff and/or with bereavement expertise, established virtual bereavement cafes in May 2021, run by staff for staff. MS Teams (video teleconferencing, chat, signposting to resources) provided a safe, supportive meeting space. Facilitated Cafes are held fortnightly, with mental health first aiders present. Ground rules emphasised respect, confidentiality, the validity of all types of grief and all deaths (pre or during the pandemic). Chat and emojis offered support. Post cafe email and phone follow-up was offered. Additional themed cafes supported: Grief Awareness Week, the Queen's death, Pregnancy or Infant loss and bespoke sessions run for teams whose colleague had died. A rapid qualitative thematic evaluation to better understand participants experience of grief and how the cafes have helped was carried out in 2022. Results Between 9-34 staff attend with new participants at each session. All types of grief have been experienced: anticipatory, complicated, cumulative and disenfranchised grief - often in combination. Participants' feedback has been thematically grouped related to their experience of the Grief Cafes, specific workplace challenges, and the impact of the pandemic on grief. Conclusions There is a significant level of unresolved and complex grief following the COVID-19 pandemic in workingage people. Impact Virtual cafes provide critical emotional support in geographically dispersed organisations. They work best linking with and driving compassionate workplace policies.

Deployment of whole genome next-generation sequencing of SARS-CoV-2 in a military maritime setting.

BACKGROUND: SARS-CoV-2 can spread rapidly on maritime platforms. Several outbreaks of SARS-CoV-2 have been reported on warships at sea, where transmission is facilitated by living and working in close quarters. Core components of infection control measures such as social distancing, patient isolation and quarantine of exposed persons are extremely difficult to implement. Whole genome sequencing (WGS) of SARS-CoV-2 has facilitated epidemiological investigations of outbreaks, impacting on outbreak management in real time by identifying transmission patterns, clusters of infection and guiding control measures. We suggest such a capability could mitigate against the impact of SARS-CoV-2 in maritime settings. METHODS: We set out to establish SARS-CoV-2 WGS using miniaturised nanopore sequencing technology aboard the Royal Fleet Auxiliary ARGUS while at sea. Objectives included designing a simplified protocol requiring minimal reagents and processing steps, the use of miniaturised equipment compatible for use in limited space, and a streamlined and standalone data analysis capability to allow rapid in situ data acquisition and interpretation. RESULTS: Eleven clinical samples with blinded SARS-CoV-2 status were tested at sea. Following viral RNA extraction and ARTIC sequencing library preparation, reverse transcription and ARTIC PCR-tiling were performed. Samples were subsequently barcoded and sequenced using the Oxford Nanopore MinION Mk1B. An offline version of the MinKNOW software was used followed by CLC Genomics Workbench for downstream analysis for variant identification and phylogenetic tree construction. All samples were correctly classified, and relatedness identified. CONCLUSIONS: It is feasible to establish a small footprint sequencing capability to conduct SARS-CoV-2 WGS in a military maritime environment at sea with limited access to reach-back support. This proof-of-concept study has highlighted the potential of deploying such technology in the future to military environments, both maritime and land-based, to provide meaningful clinical data to aid outbreak investigations.

TOCILIZUMAB for GIANT CELL ARTERITIS: BASELINE and TWELVE MONTH AUDIT DATA from the UK BRISTOL and BATH MULTIDISCIPLINARY MEETING

Background: Giant Cell Arteritis (GCA) is a systemic vasculitis involving large and medium-sized blood vessels. Treatment is with high dose glucocorticoids. Steroid-sparing agents and Tocilizumab (TCZ) are used for refractory or relapsing cases. NHS England requires all GCA patients to be discussed in a regional multidisciplinary team meeting (MDT) prior to commencing TCZ. TCZ has only been permitted for a maximum of one year;this time limitation was extended during the Covid-19 pandemic (1). The monthly virtual Bristol and Bath regional MDT started in November 2018. Objectives: We aimed to review: 1) Baseline data on all patients referred to the Bristol and Bath TCZ for GCA MDT, including demographics, clinical presentation and previous steroid-sparing agents used and 2) 12 month follow up data including number of completions, adverse effects, and fares on treatment. Methods: The TCZ MDT referral proforma, adapted from the NHS England Blueteq approval form, was reviewed for all patients referred. 12 month follow up data was obtained from clinic letters. Results: Baseline data Thirty-eight cases were referred between November 2018 and September 2021. Of these, 31 were approved for TCZ usage;100% fulflled the criteria for either refractory (n=11) or relapsing (n=20) disease. Mean age was 74 years and 74.2% were female. Average disease duration was 161.5 days for the refractory and 827.3 days for the relapsing group. 77.4% had cranial GCA, 48.4% had large vessel involvement, 45.2% had visual symptoms and 25.8% had ischaemic visual loss. The positive investigations were PET-CT (48.4%), temporal artery ultrasound (41.9%) and temporal artery biopsy (32.3%). 64.5% had trialled a steroid-sparing agent at time of referral (61.3 % metho-trexate, 9.7% azathioprine, 6.5% lefunomide), 35.5% had received intravenous methylprednisolone and 58% were receiving greater than 40mg prednisolone at the time of referral. Glucocorticoid adverse effects of osteoporosis, weight gain, cataracts and hypertension were each seen in 19.4%;whilst diabetes, neuropsychiatric symptoms and sleep disturbance were each reported in 16.1%. Those with ocular involvement tended to be referred earlier than those without (478.2 days vs 648.1 days), were referred on higher doses of glucocorticoids (71.4% vs 47.1% on ≥ 40mg) and had less steroid-sparing agents prior to referral. Follow up data In December 2021, a follow-up audit revealed 14/31 patients had completed at least 12 months of tocilizumab;5 of these had had an extension under Covid-19 exceptional guidance (mean duration of 5.2 months). Of the remaining 17: 3 patients had stopped early (1 death, 1 moved away, 1 due to adverse effects of headache and gastro-intestinal side effects), 4 had not started tocilizumab and 10 had not completed 12 months of treatment at that point. Adverse events in the 14 patients at 12 months included: liver abnormalities (2/14;14.3%), neutropenia (2/14;14.3%), thrombocytopaenia (1/14;7.1%), soft tissue infections (3/14;21.4%), urinary tract infection (1/14;7.1%) and lipid derangement (4/14 28.6%). One case of GCA relapse occurred on TCZ (mild headache and raised infammatory markers settled on small increase in prednisolone). After 12 months, mean prednisolone dose was 3mg (range 0-15mg). Conclusion: All patients approved for Tocilizumab in the GCA MDT fulflled NHS England criteria for either relapsing or refractory disease. The majority of cases had cranial disease, but almost half had either ocular or large vessel involvement, refecting a severe spectrum of disease. Cases showed a high burden of glucocorticoid toxicity. Follow up data suggests that TCZ was effective in allowing glucocorticoid weaning and disease control, but with some adverse effects. Future work to follow up patients after stopping Tocilizumab would be informative, as the twelve month limitation on treatment is likely to be re-instated.

Impact on quality of life from multi-modality treatment for lung cancer: a randomised controlled feasibility trial of surgery versus no surgery as part of multi-modality treatment in potentially resectable stage III-N2 NSCLC (the PIONEER trial)

Introduction: Optimal treatment of stage III-N2 NSCLC requires multi-modality treatment: local treatment (surgery or radiotherapy) and systemic anti-cancer therapy. There is no clear evidence of superiority for survival between surgical and non-surgical approaches and little research has explored quality of life as an endpoint (QOL). Methods: Randomised controlled feasibility study. Patients are randomised to receive multi-modality treatment 1) with surgery OR 2) without surgery. Eligible patients have ‘potentially resectable’ N2 NSCLC and have received an MDT recommendation for multimodality treatment. Sixty-six patients and their carers will be recruited from 8 UK centres. Patient/carer QOL questionnaires will be administered at baseline, weeks 6, 9, 12 and month 6, data will be analysed descriptively. Semi-structured interviews will be conducted and framework analysis applied. Results: Recruitment is ongoing (opened November 2020). Despite COVID-19 related challenges, we have opened six sites, approached 14 patients and successfully recruited nine patients (64% consent rate) and five carers. Four patients and two carers have completed the trial. Five patients (55%) have completed all outcome data to date and eight patients (89%) have received their allocated treatment. NSCLC N2 patients being assessed at MDTs at recruiting sites are being assessed for eligibility. Forty-seven N2 patients have been identified as ineligible. Reasons for ineligibility include: not suitable for surgery;referred for best supportive care;MDT decision regarding most appropriate treatment;patient choice regarding treatment;other. Conclusion: There have been challenges to site opening due to sites focusing on COVID related studies only. Three sites have only opened in the past 6 months and a further two are due to open which should increase recruitment. Despite delays we have successfully recruited nine participants and all but one have received their allocated treatment. Results will inform the design of a future fully powered randomised trial with QOL as the primary outcome.

Launching a Virtual Bereavement Café Developed and Run by Staff, for Staff, in 2 National English Public Health Organisations During the COVID-19 Pandemic

Background/aims: The COVID-19 pandemic has adversely impacted bereavement experience by restrictions: visiting the dying, funerals, family meetings, access to bereavement services. Public health work on the pandemic and other essential functions has been unrelenting. Enforced home working enhanced isolation. Many colleagues were experiencing difficult bereavements with little access to support. Methods: A grassroots group of bereaved staff or with expertise in bereavement established an infrastructure to run Virtual Bereavement Cafes by staff for staff across the 2 national public health organisations. The Chief Executive gave support. MS Teams (video teleconferencing, chat and signposting to resources) was used to provide a safe, mutually supportive space for staff to meet virtually. Cafés were 45 minutes every fortnight, facilitated with mental health first aiders present. Ground rules emphasised respect, confidentiality, the validity of all types of grief and all deaths whether pre or during the pandemic. Chat and comforting emojis were used to offer support. Post café support was provided via email and/or a call. Results: 10 cafés were held May to September 2021. Attendance 14 to 34 with new staff at each. Topics emerged from shared experiences, including anticipatory, complicated, cumulative and disenfranchised grief. Thematic synthesis of discussions and chat identified isolation, distress from limited funeral attendance, presence at death, and lack of workplace understanding. Conclusions: Virtual Bereavement Cafés have provided key emotional support during the pandemic. Improvements identified for implementation include: technical enhancements with use of interactive technologies to dynamically identify topics for discussion;increased facilitator capacity to enable break out groups and more monitoring;debrief sessions for facilitators to support their wellbeing;themed sessions publicised in advance, including practical topics;increased signposting to resources. The Cafés will now implement the learning.

How to give home BP monitoring patients the correct cuff: Using BMI as a surrogate estimate of arm circumference

Background: The key role of patient self-monitoring, already well established by large-scale forward planning initiative such the British National Health Service's (NHS) long-term plan, has been emphasised by the COVID19 pandemic. In the management of hypertension, much can be achieved through the provision of blood pressure monitors to patients, along with appropriate education and online blood pressure (BP) recording facilities. However, it is important to ensure that patients have the correct equipment to reliably measure their own blood pressures and to ensure they purchase or are supplied with validated monitors and, as undersized cuffs yield artefactually elevated BP readings, with correctly sized cuffs. Purpose: To demonstrate the use of Body Mass Index (BMI) as an estimate of Middle Upper Arm Circumference (MUAC) for purposes of blood pressure monitor cuff size requirement estimation and the application of this strategy to a national Home Blood Pressure Monitoring (HBPM) programme. Methods: The relationship between MUAC and BMI is well established;MUAC is used surrogate measure of BMI particularly in identifying underweight patients especially in environments where accurate recording of weight and height is challenging. Here, we reverse this relationship to use the BMI (one of the most commonly recorded datum in primary care patient records) to estimate patient MUACs. First, using manufacturer recommended cuff arm-circumference ranges and aggregate pre-established MUAC to BMI linear equations, we generate a simplified BMI to cuff-size scheme. Second, we apply this scheme to a UK Integrated Care System (a regional NHS organisation supporting 1.7 million adult patients in an English city) to estimate cuff requirement under NHS England's BPM@h HBPM initiative (in which patients with poorly controlled hypertension are allocated free home BP monitors). Lastly, we propose a patient-level tool for BP monitor cuff size prediction. Results: Our simplified scheme proposes the following cuff predictions: Small (S: 17-22cm): BMI <18kg/m2;Medium (M: 22-32cm): BMI ≥18 and <28kg/m2;Large (M: 32-42cm): BMI ≥28 and <38kg/m2 and Extra-large (X: 42-50cm): BMI ≥38kg/m2. In our population of approximately 157,000 adult hypertensive patients, 6,039 were eligible for a BP monitor under the NHS England's BPM@h HBPM initiative. Using our simplified scheme, we predict cuff requirements as follows: S: 2%, M: 32%, L: 46%, X: 19%. Conclusion: Patient BMIs are a useful predictor of BP monitor cuff size requirement. They are readily available or calculatable from primary care records and their application to cuff size identification will improve accuracy of BP readings in HBPM initiatives. Our preliminary results suggest that the most commonly supplied standard cuff may be unsittable for well over 50% of patients and that extra-large cuff may be required for nearly 1 in 5 patients.

Protocol design and preliminary evaluation of the REAL-Health Triple Aim, an open-cohort CVD-care optimisation initiative

Introduction: Effective treatment of cardiovascular disease (CVD) in primary care could be improved. We aim to assess the efficacy of a scalable treatment optimisation programme in unselected community populations in South East England, with the triple aim of improved blood pressure control in people with hypertension, increased high-intensity statin use in people with CVD and reduced gastrointestinal bleeding in patients on antithrombotic medication. Method: This observational study comprises an open cohort of approximately 200,000 adults at high cardiovascular risk registered with general practitioners in five South East England Clinical Commissioning Groups (CCGs). An intervention programme is planned in four of these CCGs with a further non-intervention CCG acting as a control group. The intervention will consist of: clinical guidelines and educational outreach;virtual patientreviews software;peer-performance dashboards and, where available, financial incentives. The study will examine 3 primary outcomes: 1. Diagnosed hypertension with a blood pressure <140/90mmHg;2. Diagnosed CVD on a highintensity statin;3. A cardiovascular indication for antithrombotic therapy with one or more factors for increased risk of gastrointestinal bleeding (e.g. age ≥65) on gastroprotection. A further 17 secondary outcomes related to these three aims will be assessed. Analysis: We will use an interrupted time series analysis over 18 months, representing the pre-implementation, implementation and the post-implementation phases with comparison to the control CCG and applicable national Quality and Outcomes Framework and national prescribing statistics (e.g. OpenPrescribing). Secondary outcomes include an equity impact analysis with results stratified by age, gender, ethnic group and index of deprivation. Preliminary data: We present preliminary data on Key Performance Indicators (KPIs) collected from 191 GP practices including [percentage achievement on 01/09/2019, on 01/09/2020]: 1. Patients with hypertension and most recent blood pressure ≤140/90mmHg [68.7%, 60.6%]. 2. Patients eligible for treatment with a high-intensity statin on such treatment [53.8%, 55.8%]. 3. Patients on antithrombotics with ≥1 risk factors for gastrointestinal bleeding on gastroprotection [59.0%, 60.1%]. We also present our virtual patient-review software tool and outcome visualisation dashboard. Conclusion: The REAL-Health Triple Aim initiative is a large-scale primary care cardiovascular risk reduction initiative which was launched almost contemporaneously with the United Kingdom's first SARS-CoV-2 related lockdown. Preliminary data justify the need for the Triple Aim initiative and give us an insight on the impact of the pandemic on its implementation.

Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI) [version 1;peer review: 1 approved, 1 approved with reservations]

Global infection and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are disproportionately high in certain populations, including the elderly. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit 6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months. Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics. Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection © 2020. Krutikov M et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Lessons Learned from Implementing Blended and Online Undergraduate Chemistry Laboratory Teaching during the Covid-19 Pandemic

In March 2020, the Covid-19 pandemic led to unprecedented circumstances which impacted significantly on Higher Education. Since that time, requirements for social distancing and reduced access to in-lab teaching facilities have meant a dramatic redesign of many Chemistry undergraduate laboratory courses. This chapter presents the lessons learned from the redevelopment of the 2020-2021 first-year chemistry undergraduate laboratory course at Durham University. The two pre-existing laboratory modules were converted from their traditional in-lab delivery (supported by online pre- and post-lab activities) to a blended delivery module and a fully online module. The blended module focused on the key manipulative skills students need to gain competence in to progress successfully to second year laboratory work. The fully online module focused on scientific enquiry skills. This chapter presents practical and theoretical considerations for the development of blended or online laboratory courses before discussing lessons learned from the evaluation of the process of implementing the course and the impact for students. © 2021 American Chemical Society. All rights reserved.

Understanding nurse-led care in early RA: Interview study with rheumatology nurse specialists

Background: Nurse-led care in early RA is not well defined in the literature and the current recommendations. Objectives: This study aimed to develop an understanding of what comprises nurse-led care in early RA from the perspective of rheumatology nurse specialists. Methods: This was a qualitative study using semi-structured telephone interviews with rheumatology nurse specialists in England (Summer 2020). Interviews were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis.[1] Results: Sixteen nurses were recruited and interviews lasted between 30 to 60 minutes. Seven themes were identified. Early disease management Care was characterised by evidence-based RA management provided by experienced nurse specialists with a high degree of autonomy, in the context of a rheumatology multidisciplinary team. The aims of care were to: start treatment, keep in treatment, educate and support. 'So treat to target.escalating treatment as necessary, and addressing any concerns that the patients might have' (CNS14) Addressing psychosocial needs Patients with early RA experience shock, fear, anger, grief and denial while feeling unwell with pain and fatigue. Nurses use a holistic, person-centred and empathetic approach to address psychosocial needs, building a working relationship, listening and creating trust. 'Because it all relates, and if they're stressed because they're not coping at work, then their arthritis isn't going to be so good. So everything relates to one another really' (CNS06) Monitoring treatment, disease impact and patient outcomes Nurses monitor disease activity and disease impact using validated outcome measures and by asking questions during the consultation. Good outcomes are disease control, managing disease impact, medication and side effects, wellbeing and keeping in work. 'When you get them stable, when you get them into remission, when they're happy, when they're feeling well, I think there's lots of ways you can measure that'. (CNS13) Coordinating care, referring and signposting Nurses coordinate care, refer to other health professionals and signpost patients to relevant services and charities. Lack of access to psychology expertise was highlighted. 'And whilst most of us have got some degree of understanding of.self management, or psychology.we're not psychologists' (CNS02) Providing a 'lifeline' Nurse-led telephone advice services provide a 'lifeline' for patients. If patients struggle, they can call and speak with a specialist who knows them and their RA well. 'The advice line has been a lifeline to them, to be able to speak to someone, to be able to get a response quickly to their questions, they feel very well supported, they know that they can always call us' (CNS16) Service evaluation and auditing The individual clinics are reviewed regularly. Patients are asked for feedback on their experience of appointments, if their needs were met and about changes to the service. .'It's really important to ask them initially what they expect to have from the consultation.We've always had really good feedback in general'. (CNS02) COVID-19 challenges and opportunities The pandemic caused major disruptions to the services, prohibiting most faceto-face consultations which was an essential aspect of clinical assessments. Despite the challenges imposed by the pandemic, the services adapted fast, using telephone, video clinics and digital solutions, which streamlined procedures and improved documentation and communication. 'I do have to rely on them telling me what's going on, because I can't see it at the moment' (CNS14) 'With Covid we're doing it over the telephone, and we're getting them to watch the video [injection tutorial] before we have the appointment with them' (CNS04) Conclusion: Nurse-led care in early arthritis is a specialist service, addressing complex needs of patients, using evidence based and person-centred approaches. Innovation and service improvement are seen as part of the role.

The uclpartners proactive care frameworks-optimising cvd prevention post covid. innovation to restore and improve care in the high-risk conditions and prevent heart attacks and strokes at scale

Introduction COVID-19 has disrupted pathways of care for over 12 months. Primary care has transformed dramatically with much care being provided remotely. The COVID surges and vaccination programme have reduced capacity further. People with conditions such as hypertension, cardiovascular disease and diabetes depend on regular review and treatment optimisation to keep them well. There is a high risk that continued disruption to proactive care will drive an increase in exacerbations and complications. It is likely this will drive further waves of demand for urgent care over the coming months in primary care, in emergency departments and in hospital admissions. Methods The team of GPs & pharmacists at UCLPartners, with patient and public support, developed proactive care frameworks for six conditions including atrial fibrillation, hypertension, high cholesterol and type 2 diabetes mellitus. The frameworks focus on the 'how to' of delivering care in the new world of primary care post COVID-19. They are built on 4 principles: virtual where appropriate, use of the wider workforce, step change in self-management, and use of digital resources. For each condition, the frameworks include: risk stratification tools;pathways that support remote care and deploy staff such as healthcare assistants and social prescribers to systematically support education, self-management and lifestyle change;scripts, protocols and training to guide these staff in consultations;digital tools;and resources to support treatment optimisation. The frameworks include clinical and project management support for local pathway adaptation and implementation. Results The frameworks have gained wide traction in primary care across England. There have been over 2,700 downloads of the search/stratification tools with evidence of implementation in several regions. In the UCLP geography, North East London and North Central London have adopted the frameworks for roll out across 475 GP practices and 2.8 million people. NHSEngland has now adopted the Frameworks as a key part of the NHS@Home programme with plans to support at scale national roll out. Evaluation is being commissioned. Conclusions The UCLPartners Proactive Care Frameworks provide systematic, evidence-based support to restore services post COVID: stratifying so that higher risk patients can be prioritised and workload managed;maximising remote care;optimising personalisation and support for self-care. By using a population health management approach together with comprehensive resources to support clinical management in real world primary care, the frameworks provide a platform not just to restore services but to optimise treatment and outcomes in the high-risk conditions for CVD. The widespread national traction the frameworks are gaining suggests that despite the pandemic, this brings an opportunity to deliver the NHS Long Term Plan ambitions for CVD prevention and prevent 150,000 heart attacks, strokes and cases of dementia.

Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long-term care facilities (VIVALDI): a prospective cohort study

Background SARS-CoV-2 infection represents a major challenge for long-term care facilities (LTCFs) and many residents and staff are seropositive following persistent outbreaks. We aimed to investigate the association between the SARS-CoV-2 antibody status at baseline and subsequent infection in this population. Methods We did a prospective cohort study of SARS-CoV-2 infection in staff (aged <65 years) and residents (aged >65 years) at 100 LTCFs in England between Oct 1, 2020, and Feb 1, 2021. Blood samples were collected between June and November, 2020, at baseline, and 2 and 4 months thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR testing for SARS-CoV-2 was done weekly in staff and monthly in residents. Cox regression was used to estimate hazard ratios (HRs) of a PCR-positive test by baseline antibody status, adjusted for age and sex, and stratified by LTCF. Findings 682 residents from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were detected in 226 (33%) of 682 residents and 408 (29%) of 1429 staff members. 93 (20%) of 456 residents who were antibody-negative at baseline had a PCR-positive test (infection rate 0.054 per month at risk) compared with four (2%) of 226 residents who were antibody-positive at baseline (0.007 per month at risk). 111 (11%) of 1021 staff members who were antibody-negative at baseline had PCR-positive tests (0.042 per month at risk) compared with ten (2%) of 408 staff members who were antibody-positive staff at baseline (0.009 per month at risk). The risk of PCR-positive infection was higher for residents who were antibody-negative at baseline than residents who were antibody-positive at baseline (adjusted HR [aHR] 0.15, 95% CI 0.05-0.44, p=0.0006), and the risk of a PCR-positive infection was also higher for staff who were antibody-negative at baseline compared with staff who were antibody-positive at baseline (aHR 0.39, 0.19-0.82;p=0.012). 12 of 14 reinfected participants had available data on symptoms, and 11 of these participants were symptomatic. Antibody titres to spike and nucleocapsid proteins were comparable in PCR-positive and PCR-negative cases. Interpretation The presence of IgG antibodies to nucleocapsid protein was associated with substantially reduced risk of reinfection in staff and residents for up to 10 months after primary infection. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI)

Global infection and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are disproportionately high in certain populations, including the elderly. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit 6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months. Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics. Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection. Protocol registration: ISRCTN14447421 05/06/2020.

Comparative analysis of three laboratory based serological assays for SARS-CoV-2 in an Australian cohort.

Many unanswered questions remain regarding the role of SARS-CoV-2 serological assays in this unfolding COVID-19 pandemic. These include their utility for the diagnosis of acute SARS-CoV-2 infection, past infection or exposure, correlation with immunity and the effective duration of immunity. This study examined the performance of three laboratory based serological assays, EUROIMMUN Anti-SARS-CoV-2 IgA/IgG, MAGLUMI 2000 Plus 2019-nCov IgM/IgG and EDI Novel Coronavirus (COVID-19) IgM/IgG immunoassays. We evaluated 138 samples from a reference non-infected population and 71 samples from a cohort of 37 patients with SARS-CoV-2 confirmed positive by RT-PCR. The samples were collected at various intervals of 0-45 days post symptoms onset (PSO). Specificity and sensitivity of these assays was 60.9%/71.4% (IgA) and 94.2%/63.3% (IgG) for EUROIMMUN; 98.5%/18.4% (IgM) and 97.8%/53.1% (IgG) for MAGLUMI; and 94.9%/22.5% (IgM) and 93.5%/57.1% (IgG) for EDI, respectively. When samples collected ≥14 days PSO were considered, the sensitivities were 100.0 and 100.0%; 31.0 and 82.8%; 34.5 and 57.1%, respectively. Using estimated population prevalence of 0.1, 1, and 10%, the positive predictive value of all assays remained low. The EUROIMMUN Anti-SARS-CoV-2 IgA lacked specificity for acute diagnosis and all IgM assays offered poor diagnostic utility. Seroconversion can be delayed although all patients had seroconverted at 28 days in our cohort with the EUROIMMUN Anti-SARS-CoV-2 IgG. Despite this, with specificity of only 94% this assay would not be satisfactory for seroprevalence studies in the general Australian population given this is likely to be currently <1%.