Background Despite growing enthusiasm for co-production in healthcare services and research, research on co-production practices is lacking. Multiple frameworks, guidelines and principles are available but little empirical research is conducted on ‘how to do’ co-production of research to improve healthcare services. This paper brings together insights from UK-based collaborative research partnerships on leading co-production. Its aim is to inform practical guidance for new partnerships planning to facilitate the co-production of applied health research in the future. Methods Using an auto-ethnographic approach, experiential evidence was elicited through collective sense making from recorded conversations between the research team and senior leaders of five UK-based collaborative research partnerships. This approach applies a cultural analysis and interpretation of the leaders’ behaviours, thoughts and experiences of co-production taking place in 2008–2018 and involving academics, health practitioners, policy makers and representatives of third sector organisations. Results The findings highlight a variety of practices across CLAHRCs, whereby the intersection between the senior leaders’ vision and local organisational context in which co-production occurs largely determines the nature of co-production process and outcomes. We identified four tensions in doing co-production: (1) idealistic, tokenistic vs realistic narratives, (2) power differences and (lack of) reciprocity, (3) excluding vs including language and communication, (4) individual motivation vs structural issues. Conclusions The tensions were productive in helping collaborative research partnerships to tailor co-production practices to their local needs and opportunities. Resulting variation in co-production practices across partnerships can therefore be seen as highly advantageous creative adaptation, which makes us question the utility of seeking a unified ‘gold standard’ of co-production. Strategic leadership is an important starting point for finding context-tailored solutions; however, development of more distributed forms of leadership over time is needed to facilitate co-production practices between partners. Facilitating structures for co-production can enable power sharing and boost capacity and capability building, resulting in more inclusive language and communication and, ultimately, more credible practices of co-production in research. We provide recommendations for creating more realistic narratives around co-production and facilitating power sharing between partners.

Background SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. Results We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro - generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206 + regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF , by CD14 + macrophages isolated from CD intestinal mucosa. Conclusions This study identifies SP140 as a druggable epigenetic therapeutic target for CD.

Interest in and use of co-production in healthcare services and research is growing. Previous reviews have summarized co-production approaches in use, collated outcomes and effects of co-production, and focused on replicability and reporting, but none have critically reflected on how co-production in applied health research might be evolving and the implications of this for future research. We conducted this scoping review to systematically map recent literature on co-production in applied health research in the United Kingdom to inform co-production practice and guide future methodological research. This scoping review was performed using established methods. We created an evidence map to show the extent and nature of the literature on co-production and applied health research, based on which we described the characteristics of the articles and scope of the literature and summarized conceptualizations of co-production and how it was implemented. We extracted implications for co-production practice or future research and conducted a content analysis of this information to identify lessons for the practice of co-production and themes for future methodological research. Nineteen articles reporting co-produced complex interventions and 64 reporting co-production in applied health research met the inclusion criteria. Lessons for the practice of co-production and requirements for co-production to become more embedded in organizational structures included (1) the capacity to implement co-produced interventions, (2) the skill set needed for co-production, (3) multiple levels of engagement and negotiation, and (4) funding and institutional arrangements for meaningful co-production. Themes for future research on co-production included (1) who to involve in co-production and how, (2) evaluating outcomes of co-production, (3) the language and practice of co-production, (4) documenting costs and challenges, and (5) vital components or best practice for co-production. Researchers are operationalizing co-production in various ways, often without the necessary financial and organizational support required and the right conditions for success. We argue for accepting the diversity in approaches to co-production, call on researchers to be clearer in their reporting of these approaches, and make suggestions for what researchers should record. To support co-production of research, changes to entrenched academic and scientific practices are needed. Protocol registration details: The protocol for the scoping review was registered with protocols.io on 19 October 2021: https://dx.doi.org/10.17504/protocols.io.by7epzje .

Abstract Introduction Rectal cancer (RC) is a common cancer in the UK. Treatment options include surgery, chemotherapy, radiotherapy or a combination of these in the form of neoadjuvant or adjuvant treatment. Aim To analyse the treatment type and outcomes of our RC patients. Methods We performed an analysis of prospectively collected data on patients diagnosed with RC between Jan-2013 and Dec-2020 in our trust. Details included demographics, histology, staging, treatment and mortality. Twenty patients out of 1202 were excluded due to missing information leaving 1182 for further analysis. Results 404 patients did not receive resectional surgery due to patient choice (30), inoperability of the tumour (259), or co-morbidity (115). A total of 778 patients were found to have operable disease with TNM staging as follows; Stage1–291, Stage2–231, Stage3–217, Stage4–39. Among them 302 went on to receive neo-adjuvant treatment of which 67 (22.2%) had a complete response to treatment (ypT0). The remaining 476 patients received primary surgery; 268 did not require any additional treatment and 199 went on to have adjuvant chemo/radiotherapy. Nine patients had further intervention due to incomplete resection or disease recurrence. The majority of the tumours were adenocarcinomas (97%). Other types included; malignant melanoma, neuroendocrine tumours, and squamous cell carcinomas. The overall 1-year and 5-year mortality for the group receiving primary surgery were 5.0% and 20.4%. In the neoadjuvant group these were 3.6% and 20.9%. Conclusion We present data from a large NHS trust demonstrating a multimodal approach which has enabled us to achieve good overall outcomes.

Background Interest in and use of co-production in healthcare services and research is growing. Previous reviews have summarised co-production approaches in use, collated outcomes and effects of co-production and focused on replicability and reporting, but none have critically reflected on how co-production in applied health research might be evolving and the implications of this for future research. We aim to conduct a scoping review to systematically map recent literature on co-production in applied health research in the UK to inform co-production practice and guide future methodological research. Methods Scoping review using established methods. We will created an evidence map to show the extent and nature of the literature on co-production and applied health research, based on this we described the characteristics of the articles and scope of the literature and summarised conceptualisations of co-production and how it was implemented. We will extract implications for co-production practice or future research and conduct a content analysis of this information to identify lessons for the practice of co-production and themes for future methodological research. Results We will report on lessons for the practice of co-production and themes for future research on co-production.

Introduction: Post-operative pulmonary complications in perioperative SARS-CoV- 2 infection are associated with significant morbidity and mortality. To maintain a safe cancer service, the Countess of Chester Hospital adopted “Cold-site” operating and maintained ERAS principles for patients undergoing elective colorectal cancer surgery during the pandemic. A comparative assessment of service was undertaken for benchmarking purposes. Methods: A comparative retrospective audit was undertaken of consecutive patients undergoing elective colorectal cancer surgery from May to December 2019 and compared to May to December 2020. The Somerset Cancer Registry and electronic medical case records were used to obtain the data set. Outcomes measured were;approach to surgery;stoma rate;length of stay;level of care required;post-operative complications (>Clavien-Dindo 2) and survival at 30 days. Mann-Whitney U test and Chi-squared were used for analysis. Results: There were 44 and 50 elective colorectal cancer operations in 2019 and 2020 respectively. There was a significant difference in the median age (66:70;P = 0.03) but not in ASA grade (P = 0.14). The median length of stay was 5 and 4 days respectively (P = 0.06). There was a 17% reduction in laparoscopic approach to surgery in 2020 (57% vs 40%;P = 0.10). There was no difference in the stoma rate (P = 0.7), post-operative complication rate (P = 0.6), ITU admission rate (P = 0.14), length of ITU stay (P = 0.2) and 30-day mortality rates. Conclusion: “Cold-site” operating allows robust ERAS care to be adopted to ensure comparative outcomes for patients undergoing colorectal cancer surgery and was associated with a non-significant trend to shorter hospital stay during the COVID-19 pandemic.

Abstract Aim Since December 2019, SARS-CoV-2 has dramatically impacted the global landscape. One of the biggest challenges has been the additional strain put on healthcare systems. Although there are numerous studies on the effects of COVID-19 on intensive care beds and ventilator availability, there has been little exploration into the wider impacts of COVID-19 on the provision of other services. This study was designed to explore how COVID-19 has impacted surgical service provision at a large NHS hospital. Methods We compared the number and types of general surgical procedures carried out in a tertiary centre in the six months prior to the UK COVID-19 outbreak (September 2019-February 2020) and the six months after (March 2020-August 2020). Results We found that since March 2020 there has been a 70% decrease in the amount of operations taking place, with numbers dropping from a pre-COVID total of 1761 to a post-COVID total of 529. This mainly affected elective procedures with emergency surgeries remaining relatively constant (48 pre-COVID vs 44 post-COVID). Conclusion COVID-19 has caused a significant decrease in the number of surgeries being undertaken. This is due to a combination of factors including staffing issues, reduced investigative capacity, and national mandates on the cessation of non-urgent procedures. Although this mainly affected elective operations, it will have wider implications on future NHS workload and training. The knock on effects will inevitably result in a rise in delayed and emergency presentations with worse patient outcomes.

Intro: Since December 2019, SARS-CoV-2 has had a dramatic impact on the global landscape. One of the biggest challenges has been the additional strain that the virus has put on healthcare systems. Although there has been much data on the direct affects of COVID-19 on intensive care beds and ventilator availability, there has been little exploration into the wider impacts that the restrictions brought about by COVID-19 have had on the provision of other healthcare services. We designed this study to explore how Aim: COVID-19 has impacted surgical service provision at a tertiary centre. We Methods: compared the number and types of general surgeries carried out at a single hospital in the six months prior to the initial UK COVID-19 outbreak (September 2019 - February 2020) and the six months after (March 2020 - August 2020). We found that since March 2020 there has been a 70% decrease i Results: n the number of operations being carried out, with numbers dropping from a pre-COVID surgery number of 1761 to a post-COVID number of 529. This mainly affected elective procedures however, with emergency surgeries remaining relatively constant (48 pre-COVID vs 44 post-COVID). COVID-19 has Conclusion: caused a signicant decrease in the number of surgeries being undertaken. This is due to a combination of factors including stafng issues, reduced investigation, and national mandates requesting the cessation of non-urgent procedures. Although this has mainly affected elective operations, it is likely to have a larger impact in the future as surgical waiting lists continue to grow

Abstract Aims COVID19 has placed unprecedented constraints on healthcare services. Colorectal cancer (CRC) care was one of the many areas predicted to suffer due to these additional pressures. We believe that despite the challenges posed by COVID19, we have continued to deliver a standard of care for elective and emergency CRC resection that compares favorably with the national average. Method We conducted an analysis of the elective and emergency CRC resections carried out at a tertiary center over a 10-month period (Feb-Dec 2020). Data was collated from patient, operative, and theatre records and compared to the national average as defined by the 2020 National Bowel Cancer Audit (NBOCA). Results A total of 227 patients underwent surgery (189 elective and 38 emergencies), with a median age of 69. Of these, 153 were laparoscopic (67%), 57 open (27%), and 17 robotic (7%). The median length of stay was less than the national average; 5 days for elective surgery (NBOCA: 6) and 8 days for emergencies (NBOCA: 10). Within 30 days, overall unplanned readmissions rate was 6.5% (NBOCA: 11.6%) and return to theatre was 3.2% (NBOCA: 8.4%). Elective surgery had a 90-day mortality of 1% (NBOCA: 3%) compared to 7.8% for emergencies (NBOCA: 10.5%). Conclusion Despite the added constraints of the COVID19 pandemic, CRC resection in our unit remains safe with better outcomes than the national standard. We have demonstrated that with adequate precaution and a concerted team effort, delivery of safe care with reasonable outcome is achievable.

Abstract Aims Transanal-endoscopic microsurgery (TEMS) for early rectal cancer is an attractive alternative to radical surgery. With proper patient selection, it is possible to achieve acceptable oncological outcomes with fewer complications. We aim to study the outcomes following TEMS for suspicious or proven rectal cancers performed in our unit. Method We performed a retrospective analysis of prospectively collected data between May-17 and Oct-20. The patients’ details, tumour specific data, short term outcomes, and recurrences were recorded. Results A total of 45 patients with early rectal cancer (M = 29, F = 15) were included in this study. With1 exclusion due to intraoperative rectal perforation, 44 were available for further analysis. Eleven had a diagnosis of cancer at the time of surgery, an additional 11 patients were confirmed on final histology, and 22 were benign. Final histology showed: T1=14, T2=4, T3=3 &Tx=1. The majority (68%) had clear resection margins (R1=3, R2=1, Rx = 3). Twelve patients went on to have further treatment. Seven had resectional surgery (AR = 5, APR=2) for unfavorable histology (2), residual disease (3), or recurrence (2). The other 5(23%) received chemotherapy+/-radiotherapy (unfit/patients’ choice) for unfavorable. Histology (3) or residual disease (2). Conclusion With judicious patient selection, it is possible to offer a less invasive option with acceptable oncological and patient related outcomes for suspicious and proven malignant rectal lesions. The majority of patients (84%) were able to avoid radical surgery or stoma, thereby reducing the associated morbidity. Whilst this is a single institution study, we believe with available expertise this could be widely replicated.