Search

Abstract The current research ethics review systems are composed of isolated institutional Research Ethics Committees (RECs) that develop their own standard operating procedures (SOPs), templates and so on, with low adoption of digital solutions to manage submission and review processes. This poses several challenges, such as delays, higher costs, and hindering multi-site research. We propose an online national research ethics platform that all RECs can use, with common review processes and documentation requirements following national policy. The system will scale up adoption of digital solutions to all RECs. It will reduce administrative burden and harmonize review procedures. It will also obviate the need for separate and isolated interventions such as national REC registries or clinical trial registries, as these can be generated as transactional outputs of the system. The harmonized procedures and possibility of single submission will facilitate multi-site research. Sharing of resources and expertise among RECs on the platform will enhance resilience. An e-EC system developed in India and a Regional Health research portal developed by the WHO South-East Asia office offer proof of concepts to demonstrate the feasibility of developing and using such systems. The proposed solution is ambitious but feasible. Developing the proposed system will be a vital cost-effective investment in national health infrastructure to strengthen the research ecosystem and accelerate delivery of improved healthcare innovations by reducing unnecessary delays in conducting research. To maximize benefits, concurrent efforts are needed to build researchers’ capacity and enhance the quality and efficiency of human reviews of the research proposals by REC.

Abstract Background The aim of this project is to evaluate public contributors’ experiences of their involvement in qualitative data analysis workshops during an on-going research project titled ‘Personalised Primary care for Patients with Multiple long-term conditions’. Methods Four qualitative data analysis workshops were designed and conducted between August and December 2023. We used the Cube evaluation framework (henceforth referred to as the Cube) to evaluate the workshops. The Cube suggests four domains for successful PPI (voice, agenda, change, contribute).Within Workshops One, Two and Three public contributors had to login to an account to access the Cube; this was modified in Workshop Four following feedback from public contributors. Findings Across the four workshops the Cube was completed 11 times. Across all four workshops, public contributors thought that their voice was heard, that there were diverse ways to contribute and that they led the agenda. Public contributors thought that researchers responded to their questions and issues, when necessary. Conclusion This evaluation has shown that public contributors can gain new skills and lead qualitative data analysis discussions.

Background: People with inflammatory rheumatological conditions (IRCs) are at high risk of developing other conditions including cardiovascular disease (CVD) and mood disorders. Aim: To explore perspectives of people with IRCs and healthcare practitioners (HCPs) on the content and delivery of a review consultation aimed at identification and management of multiple long-term conditions (mLTCs). Design & setting: Semi-structured interviews and focus groups with people with IRCs and HCPs in primary and secondary care. Method: People with IRCs participated in individual semi-structured interviews by telephone or online platform. HCPs (including primary and secondary care clinicians) participated in online focus groups. Data were transcribed verbatim and analysed using inductive thematic analysis. Results: Fifteen people with IRCs were interviewed; three focus groups with HCPs were conducted. The following two main themes were identified: reflecting on the value of review consultations; and what would a new review look like? Overall, people with IRCs and HCPs reflected that access to reviews is inequitable, leading to duplication of reviews and fragmentation in care. People with IRCs, at times, had difficulty conceptualising reviews, especially when discussing their future risk of conditions. People suggested that preparation before the healthcare review could align patient and HCP agendas as part of a flexible and person-centred discussion. Conclusion: Any review introduced for people with IRCs must move beyond a ‘tick-box’ exercise. To gain maximum value from a review, preparation from both patient and HCP may be required alongside a person-centred approach while ensuring they are targeted at people most likely to benefit.

Background: Opioids are frequently prescribed for persistent non-cancer pain despite limited evidence of long-term effectiveness and risk of harm. Evidence-based interventions to address inappropriate opioid prescribing are lacking. Aim: To explore perspectives of people living with persistent pain to understand barriers and facilitators in reducing opioids in the context of a pharmacist-led primary care review, and identify review components and features for optimal delivery. Design & setting: A multi-method qualitative study undertaken in the primary care setting in the UK. Method: Adults with experience of persistent pain and taking opioids participated in semi-structured interviews (n = 15, 73% female) and an online discussion forum (n = 31). The Theoretical Domains Framework (TDF) provided a framework for data collection and thematic analysis, involving deductive analysis to TDF domains, inductive analysis within domains to generate sub-themes, and sub-theme comparison to form across-domain overarching themes. The behaviour change technique taxonomy (v1) and motivational behaviour change technique classification system were used to systematically map themes to behaviour change techniques to identify potential review components and delivery features. Results: Thirty-two facilitator and barrier sub-themes for patients reducing opioids were identified across 13 TDF domains. These combined into the following six overarching themes: learning to live with pain; opioid reduction expectations; assuming a medical model; pharmacist-delivered reviews; pharmacist–patient relationship; and patient engagement. Sub-themes mapped to 21 unique behaviour change techniques, yielding 17 components and five delivery features for the proposed PROMPPT review. Conclusion: This study generated theoretically informed evidence for design of a practice pharmacist-led PROMPPT review. Future research will test the feasibility and acceptability of the PROMPPT review and pharmacist training.

Background Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person’s life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations. Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion The iFraP trial will answer important questions about the effectiveness of the new ‘iFraP’ osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407

Abstract Introduction Antimicrobial resistance (AMR) is a global public health challenge. Global efforts to decrease AMR through antimicrobial stewardship (AMS) initiatives include education and optimising the use of diagnostic technologies and antibiotics. Despite this, economic and societal challenges hinder AMS efforts. The objective of this study was to obtain insights from healthcare professionals (HCPs) on current challenges and identify opportunities for optimising diagnostic test utilisation and AMS efforts. Methods Three hundred HCPs from six countries (representing varied gross national incomes per capita, healthcare system structure, and AMR rates) were surveyed between November 2022 through January 2023. A targeted literature review and expert interviews were conducted to inform survey development. Descriptive statistics were used to summarise survey responses. Results These findings suggest that the greatest challenges to diagnostic test utilisation were economic in nature; many HCPs reported that AMS initiatives were lacking investment (32.3%) and resourcing (40.3%). High resistance rates were considered the greatest barriers to appropriate antimicrobial use (52.0%). Most HCPs found local and national guidelines to be very useful (≥ 51.0%), but areas for improvement were noted. The importance of AMS initiatives was confirmed; diagnostic practices were acknowledged to have a positive impact on decreasing AMR (70.3%) and improving patient outcomes (81.0%). Conclusion AMS initiatives, including diagnostic technology utilisation, are pivotal to decreasing AMR rates. Interpretation of these survey results suggests that while HCPs consider diagnostic practices to be important in AMS efforts, several barriers to successful implementation still exist including patient/institutional costs, turnaround time of test results, resourcing, AMR burden, and education. While some barriers differ by country, these survey results highlight areas of opportunities in all countries for improved use of diagnostic technologies and broader AMS efforts, as perceived by HCPs. Greater investment, resourcing, education, and updated guidelines offer opportunities to further strengthen global AMS efforts.

Background Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person’s life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations. Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion The iFraP trial will answer important questions about the effectiveness of the new ‘iFraP’ osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration: ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407

Objectives To determine General Practice (GP) recording of carer status and the number of patients self-identifying as carers, while self-completing an automated check-in screen prior to a GP consultation.Design A descriptive cross-sectional study.Setting 11 GPs in the West Midlands, England. Recruitment commenced in September 2019 and concluded in January 2020.Participants All patients aged 10 years and over, self-completing an automated check-in screen, were invited to participate during a 3-week recruitment period.Primary and secondary outcome measures The current coding of carers at participating GPs and the number of patients identifying themselves as a carer were primary outcome measures. Secondary outcome measures included the number of responses attained from automated check-in screens as a research data collection tool and whether carers felt supported in their carer role.Results 80.3% (n=9301) of patients self-completing an automated check-in screen participated in QUantifying the identification Of carers in general practice (STATUS QUO Study) (62.6% (n=5822) female, mean age 52.9 years (10–98 years, SD=20.3)). Prior to recruitment, the clinical code used to denote a carer was identified in 2.7% (n=2739) of medical records across the participating GPs.10.1% (n=936) of participants identified themselves as a carer. They reported feeling supported with their own health and social care needs: always 19.3% (n=150), a lot of the time 13.2% (n=102), some of the time 40.8% (n=317) and never 26.7% (n=207).Conclusions Many more participants self-identified as a carer than were recorded on participating GP lists. Improvements in the recording of the population’s caring status need to be actioned, to ensure that supportive implementation strategies for carers are effectively received. Using automated check-in facilities for research continues to provide high participation rates.

Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of the E3 ubiquitin ligase anaphase promoting complex (APC). In mechanistic studies, we uncover a critical role for APC7 during the recruitment and ubiquitination of APC substrates. In proteomics analyses of the brain from mice harboring the patient-specific APC7 mutation, we identify the chromatin-associated protein Ki-67 as an APC7-dependent substrate of the APC in neurons. Conditional knockout of the APC coactivator protein Cdh1, but not Cdc20, leads to the accumulation of Ki-67 protein in neurons in vivo, suggesting that APC7 is required for the function of Cdh1-APC in the brain. Deregulated neuronal Ki-67 upon APC7 loss localizes predominantly to constitutive heterochromatin. Our findings define an essential function for APC7 and Cdh1-APC in neuronal heterochromatin regulation, with implications for understanding human brain development and disease.

Background: Uncontrolled bleeding is the leading preventable cause of death after injury. Stop the Bleed (STB) is a bleeding control training with proposed expansion into schools. However, the attitudes of guardians, specifically those with past trauma/injury, towards expanding STB into schools are unknown. Methods: A cross-sectional survey evaluated guardian attitudes towards STB training in high schools, and compared responses between guardians based on the experience of prior trauma. Logistic regression models evaluated the association between prior trauma and guardian-reported acceptability of STB training. Results: Of 750 guardians who received the survey, 484 (64.5%) responded. Most guardians (95.3%) wanted their child trained. Few (4.2%) felt this training would be harmful; 44.9% felt their child might be held responsible if something went wrong, and 28.4% reported it might be too scary for their child. In adjusted models, guardians with prior trauma were more likely to want their child trained (odds ratio [OR] = 3.50, 95% confidence interval [CI] 1.11-15.50), and identify STB as important to them (OR = 4.07, 95% CI 1.66-12.26). Conclusion: Our results support STB training in high schools, and guardians with a trauma history may be more likely to want their child trained. Further work to understand the perceived potential harm, and work to design trauma-informed first-response trainings is warranted.

Teaching assistants and teachers (N = 186) in Cambridgeshire primary schools in the UK were invited to participate in a survey to explore the perceived impact of school-based counselling (SBC) on pupils' cognitive, social, and emotional engagement. Participants were also asked which of these factors they believed were most important to a child's educational progress. T-tests and one-way ANOVAs were conducted to explore the findings. Perceived effects of SBC were greatest on pupils' social engagement (M = 18.05, SD = 4.17), followed by emotional engagement (M = 16.71, SD = 5.24) and cognitive engagement (M = 15.08, SD = 3.96). Emotional engagement was reported as the most important factor in a child's educational progress X[superscript 2][subscript (2, n = 169)] = 77.834, p < 0.0001.

IntroductionThe engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells, and, therefore, blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine elicited serum antibodies. The emergence of SARS-CoV-2 variants has necessitated the development of adaptable assays that can be applied to assess the effectiveness of antibody-based therapeutics.MethodsThrough the testing of a range of recombinant spike proteins, we have developed a cell-based, ACE2/spike protein interaction assay that characterises monoclonal anti-spike protein antibodies and neutralising antibodies in donor serum. The assay uses high-content imaging to quantify cell-bound spike protein fluorescence.ResultsUsing spike proteins from the original “Wuhan” SARS-CoV-2 strain and the Delta and Omicron variants, we identified differential blocking activity of three monoclonal antibodies directed against the spike receptor-binding domain. Importantly, biological activity in the spike interaction assay translated to efficacy in a SARS-CoV-2 infection assay.DiscussionThe spike protein interaction assay can be used to monitor anti-spike antibodies against the major known SARS-CoV-2 variants and is readily adaptable for quantification of the impact of antibodies against new and emerging SARS-CoV-2 variants.

Saccharomyces cerevisiae Srs2, in addition to its well-documented antirecombination activity, has been proposed to play a role in promoting synthesis-dependent strand annealing (SDSA). Here we report the identification and characterization of an SRS2 mutant with a single amino acid substitution (srs2-F891A) that specifically affects the Srs2 pro-SDSA function. This residue is located within the Srs2-Rad51 interaction domain and embedded within a protein sequence resembling a BRC repeat motif. The srs2-F891A mutation leads to a complete loss of interaction with Rad51 as measured through yeast two-hybrid analysis and a partial loss of interaction as determined through protein pull-down assays with purified Srs2, Srs2-F891A, and Rad51 proteins. Even though previous work has shown that internal deletions of the Srs2-Rad51 interaction domain block Srs2 antirecombination activity in vitro, the Srs2-F891A mutant protein, despite its weakened interaction with Rad51, exhibits no measurable defect in antirecombination activity in vitro or in vivo Surprisingly, srs2-F891A shows a robust shift from noncrossover to crossover repair products in a plasmid-based gap repair assay, but not in an ectopic physical recombination assay. Our findings suggest that the Srs2 C-terminal Rad51 interaction domain is more complex than previously thought, containing multiple interaction sites with unique effects on Srs2 activity.

Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular reporters that can readily be manipulated. Cellular assays comprise genetic, molecular, and cytological reporters. The assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.

Background: People with inflammatory rheumatological conditions (IRCs) are at increased risk of common comorbidities including osteoporosis. Aim: To explore the barriers to and facilitators of implementing nurse-delivered fracture risk assessments in primary care, in the context of multimorbidity reviews for people with IRCs. Design & setting: A multi-method qualitative study in primary care. Method: As part of a process evaluation in a pilot trial, semi-structured interviews were conducted with 20 patients, two nurses, and three GPs. Twenty-four patient–nurse INCLUDE review consultations were audiorecorded and transcribed. A framework analysis was conducted using the Theoretical Domains Framework (TDF). Results: Nurses reported positive views about the value of the Fracture Risk Assessment Tool (FRAX) and they felt confident to deliver the assessments following training. Barriers to implementation, as identified by TDF, particularly related to the domains of knowledge, skills, professional roles, and environmental context. GPs reported difficulty keeping up to date with osteoporosis guidelines and voiced differing opinions about whether fracture risk assessment was the role of primary or secondary care. Lack of integration of FRAX into IT systems was a barrier to use. GPs and nurses had differing views about the nurse role in communicating risk and acting on FRAX findings; for example, explanations of the FRAX result and action needed were limited. Patients reported limited understanding of FRAX outcomes. Conclusion: The findings suggest that, with appropriate training including risk communication, practice nurses are likely to be confident to play a key role in conducting fracture risk assessments, but further work is needed to address the barriers identified.

Abstract Background Guidance for choosing face-to-face vs remote consultations (RCs) encourages clinicians to consider patient preferences, however, little is known about acceptability of, and preferences for RCs, particularly amongst patients with musculoskeletal conditions. This study aimed to explore the acceptability of, and preferences for, RC among patients with osteoporosis and rheumatoid arthritis. Methods Three UK qualitative studies, exploring patient experiences of accessing and receiving healthcare, undertaken during the pandemic, with people with osteoporosis and rheumatoid arthritis. Study team members agreed a consistent approach to conduct rapid deductive analysis using the Theoretical Framework of Acceptability (TFA) on transcripts from each data set relating to RC, facilitated by group meetings to discuss interpretations. Findings from the three studies were pooled. Results Findings from 1 focus group and 64 interviews with 35 people were included in the analysis. Participants’ attitudes to RC, views on fairness (ethicality) and sense-making (intervention coherence) varied according to their needs within the consultation and views of the pandemic. Some participants valued the reduced burden associated with RC, while others highly valued non-verbal communication and physical examination associated with face-to-face consults (opportunity costs). Some participants described low confidence (self-efficacy) in being able to communicate in RCs and others perceived RCs as ineffective, in part due to suboptimal communication. Conclusions Acceptability of, and preferences for RC appear to be influenced by societal, healthcare provider and personal factors and in this study, were not condition-dependant. Remote care by default has the potential to exacerbate health inequalities and needs nuanced implementation.

Introduction: Understanding patients' experiences is important when developing interventions for people living with persistent pain. Interviews and focus groups are frequently used to capture beliefs, views, and perspectives. These methods often require a commitment to a predetermined date and time that may present a barrier to participation. An asynchronous online discussion forum, specifically designed for research purposes, provides an alternative and potentially more accessible method for participation. In this article we discuss a bespoke online discussion forum, the Q-PROMPPT blog, as a case example. Methods: We describe how we developed the Q-PROMPPT blog, with patient and public involvement, and its use as an innovative method for qualitative data collection in the context of developing an intervention for patients prescribed opioids for persistent pain. Drawing on our experiences we discuss the following areas: planning and design, participant recruitment and registration, and participant experience and engagement. Results: We identify and address key concerns for each area of the Q-PROMPPT blog: planning and design: choosing software, assigning roles, designing the interface to promote usability; recruitment of participants: recruiting eligible participants, participant anonymity; participant experience and engagement: mitigating risk of harm, facilitating discussions, planning for forum close. Conclusion: Based on our lessons learnt, we outline recommendations for using a bespoke online discussion forum as a qualitative method to inform intervention development for people living with persistent pain. These include collaboration with information communication technology teams, co-design with patient and public partners, minimising risk of imposter participants and developing trust and online community identity. [ABSTRACT FROM AUTHOR]

Background: Opioids are frequently prescribed for persistent non-cancer pain despite limited evidence of long-term effectiveness and risk of harm. Evidence-based interventions to address inappropriate opioid prescribing are lacking. Aim: To explore perspectives of people living with persistent pain to understand barriers and facilitators in reducing opioids in the context of a pharmacist-led primary care review, and identify review components and features for optimal delivery. Design & setting: A multi-method qualitative study undertaken in the primary care setting in the UK. Method: Adults with experience of persistent pain and taking opioids participated in semi-structured interviews (n = 15, 73% female) and an online discussion forum (n = 31). The Theoretical Domains Framework (TDF) provided a framework for data collection and thematic analysis, involving deductive analysis to TDF domains, inductive analysis within domains to generate sub-themes, and sub-theme comparison to form across-domain overarching themes. The behaviour change technique taxonomy (v1) and motivational behaviour change technique classification system were used to systematically map themes to behaviour change techniques to identify potential review components and delivery features. Results: Thirty-two facilitator and barrier sub-themes for patients reducing opioids were identified across 13 TDF domains. These combined into the following six overarching themes: learning to live with pain; opioid reduction expectations; assuming a medical model; pharmacist-delivered reviews; pharmacist-patient relationship; and patient engagement. Sub-themes mapped to 21 unique behaviour change techniques, yielding 17 components and five delivery features for the proposed PROMPPT review. [ABSTRACT FROM AUTHOR]

Background: People with inflammatory rheumatological conditions (IRCs) are at high risk of developing other conditions including cardiovascular disease (CVD) and mood disorders. Aim: To explore perspectives of people with IRCs and healthcare practitioners (HCPs) on the content and delivery of a review consultation aimed at identification and management of multiple long-term conditions (mLTCs). Design & setting: Semi-structured interviews and focus groups with people with IRCs and HCPs in primary and secondary care. Method: People with IRCs participated in individual semi-structured interviews by telephone or online platform. HCPs (including primary and secondary care clinicians) participated in online focus groups. Data were transcribed verbatim and analysed using inductive thematic analysis. Results: Fifteen people with IRCs were interviewed; three focus groups with HCPs were conducted. The following two main themes were identified: reflecting on the value of review consultations; and what would a new review look like? Overall, people with IRCs and HCPs reflected that access to reviews is inequitable, leading to duplication of reviews and fragmentation in care. People with IRCs, at times, had difficulty conceptualising reviews, especially when discussing their future risk of conditions. People suggested that preparation before the healthcare review could align patient and HCP agendas as part of a flexible and person-centred discussion. Conclusion: Any review introduced for people with IRCs must move beyond a 'tick-box' exercise. To gain maximum value from a review, preparation from both patient and HCP may be required alongside a person-centred approach while ensuring they are targeted at people most likely to benefit. [ABSTRACT FROM AUTHOR]