Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis

BACKGROUND: There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. OBJECTIVE: To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. METHODS: Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane-Armitage trend test implemented in PLINK. RESULTS: One SNP in the LPP gene, rs1464510, showed significant association with JIA (p(trend)=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (p(trend)=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (p(trend)=0.005, OR=1.88, 95% CI 1.2 to 2.94). CONCLUSIONS: Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

<p>Objectives: Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.</p> <p>Methods: Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.</p> <p>Results: Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.</p> <p>Conclusions: A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.</p&gt

Seven features of safety in maternity units: a framework based on multisite ethnography and stakeholder consultation

Background: Reducing avoidable harm in maternity services is a priority globally. As well as learning from mistakes, it is important to produce rigorous descriptions of ‘what good looks like’. Objective: We aimed to characterise features of safety in maternity units and to generate a plain language framework that could be used to guide learning and improvement. Methods: We conducted a multisite ethnography involving 401 hours of non-participant observations 33 semistructured interviews with staff across six maternity units, and a stakeholder consultation involving 65 semistructured telephone interviews and one focus group. Results: We identified seven features of safety in maternity units and summarised them into a framework, named For Us (For Unit Safety). The features include: (1) commitment to safety and improvement at all levels, with everyone involved; (2) technical competence, supported by formal training and informal learning; (3) teamwork, cooperation and positive working relationships; (4) constant reinforcing of safe, ethical and respectful behaviours; (5) multiple problem-sensing systems, used as basis of action; (6) systems and processes designed for safety, and regularly reviewed and optimised; (7) effective coordination and ability to mobilise quickly. These features appear to have a synergistic character, such that each feature is necessary but not sufficient on its own: the features operate in concert through multiple forms of feedback and amplification. Conclusions: This large qualitative study has enabled the generation of a new plain language framework—For Us—that identifies the behaviours and practices that appear to be features of safe care in hospital-based maternity units

Food restriction reduces neurogenesis in the avian hippocampal formation

The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis) in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the hypothesis that the response to stressors in the avian hippocampal formation is homologous to that of the mammalian hippocampus

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Digital First Primary Care for those with multiple long-term conditions: a rapid review of the views of stakeholders

Background General practices are facing challenges such as rising patient demand and difficulties recruiting and retaining general practitioners. Greater use of digital technology has been advocated as a way of mitigating some of these challenges and improving patient access. This includes Digital First Primary Care, when a patient’s first contact with primary care is through a digital route, either through a laptop or smartphone. The use of Digital First Primary Care has been expedited since COVID-19. There is little evidence of staff experiences of using Digital First Primary Care with more complex patients, such as those with multiple long-term conditions. Objective To understand the experiences of those with multiple long-term conditions of Digital First Primary Care from the perspectives of healthcare professionals and stakeholders. Design This was a qualitative evaluation, comprised of four distinct work packages: Work package 1: Locating the study within the wider context, engaging with literature, and co-designing the study approach and research questions with patients. Work package 2: Interviews with health professionals working across general practice and key expert topic stakeholders, including academics and policy-makers. Work package 3: Analysis of data and generation of themes, and testing findings with patients. Work package 4: Synthesis, reporting and dissemination. Results The study commenced in January 2021 and in total 28 interviews were conducted with 14 health professionals and 15 stakeholders between January and August 2022. From the perspective of health professionals, Digital First Primary Care approaches could enable patients to speak with a clinician more quickly than traditional approaches. Those with multiple long-term conditions could submit healthcare readings from home, though health professionals felt patients may struggle navigating digital systems not designed to capture the nuances associated with living with multiple conditions. Clinicians expressed preferences for seeing patients face-to-face, particularly those with multiple long-term conditions, to identify non-verbal cues about a patient’s health. Digital First Primary Care approaches provided an opportunity for clinicians to engage with the carers of patients living with multiple long-term conditions, yet there were concerns around obtaining consent and confidentiality. There remain debates among stakeholders about the nature and extent to which Digital First Primary Care impacts on staff workload. Limitations At the time of data collection, general practices were facing considerable pressure to deliver care and respond to the COVID-19 pandemic. While it was originally intended that the study would include interviews with patients with multiple long-term conditions and their carers, none of the general practices that took part in the study were willing and/or able to recruit patients and carers in the time available. Conclusions The rapid implementation of Digital First Primary Care, at a time of immense pressures, meant there has been little time for considering the impact on patients, including those with multiple long-term conditions. The impacts on care continuity depended largely on how surgeries implemented their approaches. Staff and stakeholders felt that Digital First Primary Care, as an additional route for accessing primary care, could be useful for patients with multiple long-term conditions but not at the expense of face-to-face consultations. Future work Future research obtaining patient and carer views of digital-first approaches, understanding the impacts on carers and how approaches are designed with patients with more complex conditions in mind, is essential. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 16/138/31) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 21. See the NIHR Funding and Awards website for further award information. Plain language summary Healthcare professionals want to provide the best primary care in the face of increasing pressures, as well as improve access to care for patients. Digital First Primary Care is one response to this situation, when a patients’ first contact with primary care is through a digital route, either through a laptop or smartphone. Online systems allow the patient to provide information to their practice about their symptoms or needs and request a response from a health professional. Our study aimed to understand how Digital First Primary Care works for healthcare professionals providing care to increasing numbers of patients with multiple long-term conditions and their carers. Firstly, we examined the relatively limited existing findings and then interviewed healthcare professionals and key stakeholders experienced in digital approaches within primary care (e.g. from policy organisations, universities and the National Health Service). While we attempted to speak to patients and carers directly, unfortunately the pressures in general practice meant we were unable to do so. However, the study was co-designed with patients. Healthcare professionals and stakeholders felt that patients with multiple long-term conditions faced additional challenges with the use of Digital First Primary Care compared to other patients. For example, they reported difficulties navigating online forms and not being able to speak with a general practitioner who knew them well. There were differing views from healthcare professionals and stakeholders about how far Digital First Primary Care could help staff in general practice and enhance care. For some clinicians, the workload was easier to manage and some simple tasks (e.g. sick notes) could be completed quickly. This could reduce stress for staff and mean more patients could be seen per day. Others felt that the digital system had shortcomings. This could be important for patients with multiple long-term conditions; for example, when a digital form may not fully inform the general practitioner as to the exact nature of the problem, potentially requiring a further follow-up appointment. Health professionals reported that carers of patients with multiple long-term conditions generally liked the new systems as they helped to improve contact with general practice staff. The summary was co-authored by members of the BRACE Patient and Public Involvement group. Scientific summary Background Digital First Primary Care has become widespread in England, particularly since the COVID-19 pandemic. Digital First Primary Care is when a patients’ first contact with primary care is through a digital route, either through a laptop or smartphone. The design of Digital First Primary Care platforms varies by commercial provider, although the main principles are the same. The patient inputs their symptoms and concerns through a digital platform, either via a set of questions within a digital algorithm or through a free text submission. The patient is then given an appropriate response, which could be from a staff member within the practice or automatically generated by the algorithm. The consultation which results may be traditional in nature, for example by telephone or face-to-face, or be in the form of a message from a health professional to a patient or a video consultation. These approaches have been advocated by policy-makers in England since 2016, as it is believed they can enable clinicians to prioritise the care of patients. Despite the policy shift towards digital approaches, most general practitioner (GP) surgeries were not operating in this way in early 2020, with an analysis of primary care data suggesting that 13–15% of consultations were conducted remotely in January 2020. The COVID-19 pandemic has seen a rapid change in modes of service delivery in general practice, with all GP surgeries having to quickly adapt their services and offer some form of non-face-to-face consultation, to prevent viral transmission. Several studies have been conducted on the use of digital approaches in the National Health Service (NHS). The findings from these studies are wide-ranging. To summarise, digital approaches can provide a benefit to both staff and patients (e.g. greater convenience, including no need to travel to a general practice, and better monitoring of conditions), although there are some challenges. These include issues such as remote consultations taking longer than face-to-face care, potential problems with missed or delayed diagnoses, safeguarding issues, marginalising those who are digitally excluded due to poverty and digital literacy and seeing an increase in referrals to wider services. A mapping of the literature identified potential issues for patients with more complex health conditions accessing digital approaches, as well as the impact on staff in general practice, such as an increased clinical workload. Notably, there is a paucity of evidence in relation to staff experiences of using digital approaches with patients living with multiple long-term conditions. This rapid evaluation examined the views of health professionals in general practice and expert stakeholders to understand how the introduction of Digital First Primary Care influences the nature of the care delivered, any facilitators or barriers and how its use may help patients living with multiple long-term conditions. The findings provide insights that are helpful to primary care NHS staff treating patients with multiple long-term health conditions. Objectives Originally, our aim was to understand the experiences of those with multiple long-term conditions of Digital First Primary Care from the perspectives of patients, their carers and healthcare professionals. However, due to challenges related to COVID-19, GP practices were unable to recruit patients/carers to the study. The team reviewed and refined the research questions with respect to the ongoing challenges and changes occurring in general practice more widely. As a result, our research questions have been amended not only due to recruitment challenges, but also how general practice has responded to the COVID-19 pandemic. The research questions addressed in this rapid evaluation are: What is the experience of Digital First Primary Care for health professionals and stakeholders (including academics, policy makers and Digital First Primary Care providers), both before and during the COVID-19 pandemic? What is the impact of Digital First Primary Care on the nature of consultations, from the perspective of health professionals and stakeholders and for patients with multiple long-term conditions and their carers? This includes aspects of communication, timeliness of care and continuity of care. What, if any, are the advantages or disadvantages of Digital First Primary Care for health professionals when providing care for patients with multiple long-term conditions? What lessons can be learnt from staff and stakeholders, for future service delivery for patients with multiple long-term conditions in primary care? Are there individual groups within the community where there is particular learning for future service provision? Methods The evaluation comprised four interlinked work packages (WPs): WP1. Locating the study within the wider context, engaging with literature, as well as co-designing the study approach and research questions with patients–engaging with relevant literature on the use of Digital First Primary Care services by patients with multiple long-term conditions; a workshop with patients [members of the BRACE patient and public involvement (PPI) group] to shape the research questions (September 2020) as well as co-design research tools alongside continued engagement during data collection, analysis, and write up of findings. WP2. Interviews with health professionals working across general practice and key expert topic stakeholders–through in-depth interviews with GPs and nurses, at eight purposively selected general practice sites, identified via a range of strategies; analysis of data; testing findings with members from our BRACE steering group and BRACE PPI panel. The study included a variety of general practices covering differences across: (1) practice size; (2) mix of urban and rural; (3) the ethnic composition of patients; (4) the number of patients registered aged 65 years and over; (5) the nature of the digital-first applications implemented. Individual interviewees, 14 in all, were identified and approached through contacts in general practices. We also interviewed expert stakeholders (n = 15) from academia, policy think tanks and primary care-related member organisations. WP3. Analysis of data, generation of themes and testing findings with patients and carers–Data collection was undertaken between April and August 2022. We adopted a pragmatic approach to enable a comprehensive analysis within a rapid timescale: the collection and analysis of interview data were completed in parallel and facilitated through the use of one-page summaries of codes, frequent team meetings, data analysis workshops and systematic categorisation and coding according to an analytical framework based on the relevant literature identified in WP1. WP4. Synthesis, reporting and dissemination–Synthesis across WP1–3 and writing of the final report. Sharing of the findings with leading researchers and organisations in this field. Results We undertook interviews across eight general practice sites completing 14 interviews. Six of our eight practices were situated in rural locations, five were part of a single GP super-partnership and one practice was vertically integrated with an acute trust, while all practices used one of two different digital-first providers. All practices had introduced a programme of Digital First Primary Care prior to the COVID-19 pandemic, although its use had increased dramatically as a result of the pandemic. In addition, we undertook a further 15 interviews with a purposive selection of expert stakeholders. Owing to the small sample size, our findings cannot be assumed to be representative of general practice nationally, but they provide detailed insight from a diverse sample of practices where learning may be transferable to other primary care settings. The findings provide valuable insights into the use of Digital First Primary Care, both pre and post the COVID-19 pandemic. The implementation of Digital First Primary Care by health professionals providing care to patients with multiple long-term conditions The COVID-19 pandemic led to the rapid adoption and extensive roll out of Digital First Primary Care on a larger scale than pre-pandemic. The implementation of Digital First Primary Care across general practice was at speed and there was little opportunity for health care professionals to reflect on the impact that such an introduction would have on patient groups, such as those with multiple long-term conditions. In addition, the participants interviewed in our study felt that little consideration was given to the impact that the widespread use of these approaches might have on healthcare professionals who care for those with multiple long-term conditions. Some healthcare professionals felt that the introduction of Digital First Primary Care had led to an increase in demand from patients, as it was easier to access services in general practice. As a result, health professionals reported restricting the times Digital First Primary Care was available to patients in order to manage their workload and, ultimately, limited access (e.g. closing Digital First Primary Care platforms over weekends or for set times during the day). It was perceived by interviewees that patients with multiple long-term conditions may face additional challenges with the use of Digital First Primary Care compared to other patients. These challenges included navigating Digital First Primary Care systems (particularly those systems that used digital questionnaires for patients to report their symptoms/the reason they were seeking to consult, which followed algorithm approaches and restricted the opportunity to provide a descriptive narrative) and, potentially, reducing the likelihood of being able to speak with a health professional who knew them and their conditions well. Advantages and disadvantages of Digital First Primary Care for patients with multiple long-term conditions from the perspective of health professionals and stakeholders Participants reported that Digital First Primary Care could provide some benefits to patients with multiple long-term conditions, such as being seen or having their health-related queries addressed more quickly, receiving an initial response from their general practice within 1–2 days for non-urgent matters and avoiding the need to wait in long telephone queues for appointments. Where this was the case, it reduced the need for unnecessary face-to-face appointments and supported patients’ preferences where possible. Digital First Primary Care was also reported to be useful for patients with some long-term health conditions (e.g. diabetes, cardiovascular conditions, mental health conditions and hearing loss). For example, health professionals felt that patients with multiple long-term conditions found Digital First Primary Care platforms useful when submitting readings (e.g. blood sugar levels, blood pressure) from home compared to coming into the general practice, a feature which was particularly helpful for patients with well-managed long-term conditions. In addition, participants felt that younger patients, those working full-time and those who did not speak English as a first language (if translation was available within the system) benefitted from Digital First Primary Care. However, patient group participants who it was felt may benefit less from Digital First Primary Care included those who are older/frail and those without access to digital technology (or the skills or abilities to use it). Participants felt that there were some notable drawbacks when using Digital First Primary Care programmes for patients with multiple long-term conditions. Participants had concerns regarding how the introduction and application of Digital First Primary Care programmes impacts the quality of relationships patients have with healthcare professionals, as well as the impact on patient safety. Digital First Primary Care also puts the onus on the patient to articulate their problem through written means, and this can be challenging for patients who have difficulties with literacy. Further, several health professionals expressed a preference for seeing patients face-to-face, particularly those with multiple long-term conditions, so as to have the opportunity to holistically assess the patient. Finally, the participants felt that the carers of patients with long-term conditions may benefit from Digital First Primary Care as they can have more direct communication with healthcare professionals and can be more actively involved in their care. However, there are some concerns regarding confidentiality, privacy and consent when it comes to carers accessing medical information. Impact of Digital First Primary Care on the general-practice workforce within and outside of consultations with patients with multiple long-term conditions With regards to healthcare professionals, Digital First Primary Care can offer advantages in terms of better information sharing and communication across staff and patients, improved relationships with patients and greater efficiencies and flexibility. However, some felt that Digital First Primary Care was detrimental to the clinician–patient relationship, creating some inefficiencies. There were also concerns raised over the confidence staff have in their own clinical decision-making when using Digital First Primary Care and the issue of increased (unmanageable) patient demand. Conclusions Conducting interviews with clinical general-practice staff and expert stakeholders following the height of the pandemic was challenging. Useful insights have, nevertheless, been obtained. Digital First Primary Care approaches have been rapidly rolled out and COVID-19 has dramatically changed the way in which general practice operates. The implementation of Digital First Primary Care has been undertaken at great speed, with many in general practice reconsidering how best to use a suite of digital approaches, from initial patient contact to consultation, at a time of immense pressures on staff. The push for greater access to general practice and the corresponding focus on seeing and speaking to a patient rapidly have occurred at the expense of other aspects of general-practice care which the health professionals and stakeholders who were interviewed felt are valued by patients with multiple long-term conditions. These included continuity of care (particularly during the COVID-19 pandemic) and an established doctor–patient relationship which enables the clinician and patient to have clear communication. For the participants in our study, the overwhelming view was that Digital First Primary Care could be useful for patients with multiple long-term conditions, but it should be available in addition to, not at the expense of, face-to-face consultations. The authors see that there is important future work in obtaining the views of patients and their carers and comparing those alongside the views of health professionals and stakeholders obtained in this study; a cost-effectiveness analysis across providers; and understanding how individual providers of Digital First Primary Care are designed with the needs of complex patients in mind. Funding This award was funded by the N