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Abstract Background In response to concerns about high hospital mortality rates, patient and carer complaints, a Mid Staffordshire NHS Foundation Trust public inquiry was conducted at the request of the UK government. This inquiry found serious failures in the quality of basic care provided and as a consequence, recommended that patients should have more regular visits, organised at predictable times from nursing staff. Intentional rounding, also known as nursing ward rounds, was widely adopted to meet this need. Objective To test, refine or refute eight programme theories to understand what works, for whom, and in what circumstances. Setting Six wards (older people and acute wards) in three NHS trusts in England. Participants Board level and senior nursing managers (N = 17), nursing ward staff (N = 33), allied health and medical professionals (N = 26), patients (N = 34) and relatives (N = 28) participated in an individual, in-depth interview using the realist method. In addition, ward-based nurses (N = 39) were shadowed whilst they conduced intentional rounds (240 rounds in total) and the direct care of patients (188 h of patient care in total) was observed. Methods The mixed methods design included: Phase (1) Theory development - A realist synthesis was undertaken to identify any programme theories which were tested, refined and/or refuted, using data from phases 2 and 3; Phase (2) A survey of all English NHS acute Trusts; Phase (3) Six case studies of wards involving realist interviews, shadowing and non-participant observations, analysis of ward outcome and cost data; and Phase (4) Synthesis of findings from phases 1, 2 and 3. Results The realist synthesis identified eight programme theories of intentional rounding: ‘Consistency and comprehensiveness’, ‘Accountability’, ‘Visibility of nurses’, ‘Anticipation’, ‘Allocated time to care’, ‘Nurse-patient relationships’, ‘Multi-disciplinary teamwork and communication’ and ‘Patient empowerment’. Key findings showed that of the original eight programme theories of intentional rounding, only two partially explained how the intervention worked (‘Consistency and comprehensiveness’ and ‘Accountability’). Of the remaining six programme theories, the evidence for two was inconclusive (‘Visibility of nurses’ and ‘Anticipation’) and there was no evidence for four (‘Allocated time to care’; ‘Nurse-patient relationships’; ‘Multi-disciplinary teamwork and communication’; and ‘Patient empowerment’). Conclusions This first theory-informed evaluation of intentional rounding, demonstrates that the effectiveness of intentional rounding in the English healthcare context is very weak. Furthermore, the evidence collected in this study has challenged and refuted some of the underlying assumptions about how intentional rounding works. This study has demonstrated the crucial role context plays in determining the effectiveness of an intervention and how caution is needed when implementing interventions developed for the health system of one country into another.

Summary: Background: The malignant childhood brain tumour, medulloblastoma, is classified clinically into molecular groups which guide therapy. DNA-methylation profiling is the current classification ‘gold-standard’, typically delivered 3–4 weeks post-surgery. Pre-surgery non-invasive diagnostics thus offer significant potential to improve early diagnosis and clinical management. Here, we determine tumour metabolite profiles of the four medulloblastoma groups, assess their diagnostic utility using tumour tissue and potential for non-invasive diagnosis using in vivo magnetic resonance spectroscopy (MRS). Methods: Metabolite profiles were acquired by high-resolution magic-angle spinning NMR spectroscopy (MAS) from 86 medulloblastomas (from 59 male and 27 female patients), previously classified by DNA-methylation array (WNT (n = 9), SHH (n = 22), Group3 (n = 21), Group4 (n = 34)); RNA-seq data was available for sixty. Unsupervised class-discovery was performed and a support vector machine (SVM) constructed to assess diagnostic performance. The SVM classifier was adapted to use only metabolites (n = 10) routinely quantified from in vivo MRS data, and re-tested. Glutamate was assessed as a predictor of overall survival. Findings: Group-specific metabolite profiles were identified; tumours clustered with good concordance to their reference molecular group (93%). GABA was only detected in WNT, taurine was low in SHH and lipids were high in Group3. The tissue-based metabolite SVM classifier had a cross-validated accuracy of 89% (100% for WNT) and, adapted to use metabolites routinely quantified in vivo, gave a combined classification accuracy of 90% for SHH, Group3 and Group4. Glutamate predicted survival after incorporating known risk-factors (HR = 3.39, 95% CI 1.4–8.1, p = 0.025). Interpretation: Tissue metabolite profiles characterise medulloblastoma molecular groups. Their combination with machine learning can aid rapid diagnosis from tissue and potentially in vivo. Specific metabolites provide important information; GABA identifying WNT and glutamate conferring poor prognosis. Funding: Children with Cancer UK, Cancer Research UK, Children’s Cancer North and a Newcastle University PhD studentship.

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.

Objective To estimate vaccination coverage among children under the age of five attending the paediatric emergency department (PED) using tetanus and MMR vaccination as a proxy.Design A cross-sectional observational study with a single data collection point for each participant.Setting A single large PED in Greater Manchester, England.Participants Children (under 5 years old) attending the PED during October 2021. Participation was ‘opt-out’ and parents/carers were given until the end of the following month to request that their child’s data be excluded.Primary and secondary outcome measures The primary outcome of interest was the percentage of children who were up-to-date with their routine childhood vaccinations at their time of attendance to the PED. Secondary outcome measures were the percentage of children who had received age-appropriate tetanus and MMR vaccination, and how these compared with local population data at the ages of 1, 2 and 5 years of age.Results One-third of under-5s in this study had unmet vaccination need and were missing at least one dose of either MMR or tetanus-containing vaccine. In older age groups, many were missing their tetanus boosters and only 1 in 5 of those eligible had received two doses of MMR. Those in younger age groups had vaccination coverage levels comparable to the local data, but still below the target of 95%.Conclusions Those children eligible for preschool boosters (tetanus and MMR2) appear to have considerable unmet vaccination need. While the pandemic has had an impact, the observation that MMR2 uptake is considerably lower than tetanus booster (when they are scheduled together) warrants further investigation. Catch-up campaigns for MMR2 should focus on this cohort of children and the PED may offer an opportunity for an intervention.Trial registration number NCT04485624.

Abstract Background UK equality law and National Health Service (NHS) policy requires racial equality in job appointments and career opportunities. However, recent national workforce race equality standard (WRES) data show that nearly all NHS organisations in the UK are failing to appoint ethnically diverse candidates with equivalent training and qualifications as their white counterparts. This is problematic because workforce diversity is associated with improved patient outcomes and other benefits for staff and organisations. Aim To better understand the reasons behind underrepresentation of ethnically diverse candidates in first NHS healthcare jobs post-qualification and to identify any structural or systemic barriers to employment for such groups. Methods The study was informed by critical theory and the authors’ interdisciplinary perspectives as educators and researchers in the healthcare professions. Data collected from semi-structured face-to-face interviews with 12 nurse and physiotherapy recruiting managers from two NHS trusts in London were analysed using a healthcare workforce equity and diversity conceptual lens we developed from the literature. Using this lens, we devised questions to examine six dimensions of equity and diversity in the interview data from recruiting managers. Results Recruiting managers said they valued the benefits of an ethnically diverse workforce for patients and their unit/organisation. However, their adherence to organisational policies for recruitment and selection, which emphasise objectivity and standardisation, acted as constraints to recognising ethnicity as an important issue in recruitment and workforce diversity. Some recruiting managers sense that there are barriers for ethnically diverse candidates but lacked information about workforce diversity, systems for monitoring recruitment, or ways to engage with staff or candidates to talk about these issues. Without this information there was no apparent problem or reason to try alternative approaches. Conclusion These accounts from 12 recruiting managers give a ‘backstage’ view into the reasons behind ethnic inequalities in recruitment to first healthcare job in the UK NHS. Adherence to recruitment and selection policies, which aim to support equality through standardisation and anonymisation, appear to be limiting workforce diversity and creating barriers for ethnically diverse candidates to attain the jobs that they are trained and qualified for. The Healthcare Workforce Equity + Diversity Lens we have developed can help to ‘raise the curtain on the equality theatre’ and inform more inclusive approaches to recruitment such as contextualised recruitment or effective allyship between employers and universities.

Fibroblast growth factor 21 (FGF21) is a promising therapeutic agent for treatment of type 2 diabetes (T2D) and non-alcoholic steatohepatitis (NASH). We show that therapeutic levels of FGF21 were achieved following subcutaneous (s.c.) administration of mRNA encoding human FGF21 proteins. The efficacy of mRNA was assessed following 2-weeks repeated s.c. dosing in diet-induced obese (DIO), mice which resulted in marked decreases in body weight, plasma insulin levels, and hepatic steatosis. Pharmacokinetic/pharmacodynamic (PK/PD) modelling of several studies in both lean and DIO mice showed that mRNA encoding human proteins provided improved therapeutic coverage over recombinant dosed proteins in vivo. This study is the first example of s.c. mRNA therapy showing pre-clinical efficacy in a disease-relevant model, thus, showing the potential for this modality in the treatment of chronic diseases, including T2D and NASH.

In recent years, researchers have begun to explore the use of Distributed Ledger Technologies (DLT), also known as blockchain, in health data sharing contexts. However, there is a significant lack of research that examines public attitudes towards the use of this technology. In this paper, we begin to address this issue and present results from a series of focus groups which explored public views and concerns about engaging with new models of personal health data sharing in the UK. We found that participants were broadly in favour of a shift towards new decentralised models of data sharing. Retaining ‘proof’ of health information stored about patients and the capacity to provide permanent audit trails, enabled by immutable and transparent properties of DLT, were regarded as particularly valuable for our participants and prospective data custodians. Participants also identified other potential benefits such as supporting people to become more health data literate and enabling patients to make informed decisions about how their data was shared and with whom. However, participants also voiced concerns about the potential to further exacerbate existing health and digital inequalities. Participants were also apprehensive about the removal of intermediaries in the design of personal health informatics systems.

Lipid nanoparticles (LNPs) are the most clinically advanced delivery system for RNA-based drugs but have predominantly been investigated for intravenous and intramuscular administration. Subcutaneous administration opens the possibility of patient self-administration and hence long-term chronic treatment that could enable messenger RNA (mRNA) to be used as a novel modality for protein replacement or regenerative therapies. In this study, we show that subcutaneous administration of mRNA formulated within LNPs can result in measurable plasma exposure of a secreted protein. However, subcutaneous administration of mRNA formulated within LNPs was observed to be associated with dose-limiting inflammatory responses. To overcome this limitation, we investigated the concept of incorporating aliphatic ester prodrugs of anti-inflammatory steroids within LNPs, i.e., functionalized LNPs to suppress the inflammatory response. We show that the effectiveness of this approach depends on the alkyl chain length of the ester prodrug, which determines its retention at the site of administration. An unexpected additional benefit to this approach is the prolongation observed in the duration of protein expression. Our results demonstrate that subcutaneous administration of mRNA formulated in functionalized LNPs is a viable approach to achieving systemic levels of therapeutic proteins, which has the added benefits of being amenable to self-administration when chronic treatment is required.

Abstract To determine if apparent diffusion coefficients (ADC) can discriminate between posterior fossa brain tumours on a multicentre basis. A total of 124 paediatric patients with posterior fossa tumours (including 55 Medulloblastomas, 36 Pilocytic Astrocytomas and 26 Ependymomas) were scanned using diffusion weighted imaging across 12 different hospitals using a total of 18 different scanners. Apparent diffusion coefficient maps were produced and histogram data was extracted from tumour regions of interest. Total histograms and histogram metrics (mean, variance, skew, kurtosis and 10th, 20th and 50th quantiles) were used as data input for classifiers with accuracy determined by tenfold cross validation. Mean ADC values from the tumour regions of interest differed between tumour types, (ANOVA P

Abstract MRI has a vital role in the assessment of intracranial lesions. Conventional MRI has limited specificity and multiparametric MRI using diffusion-weighted imaging, perfusion-weighted imaging and magnetic resonance spectroscopy allows more accurate assessment of the tissue microenvironment. The purpose of this educational pictorial review is to demonstrate the role of multiparametric MRI for diagnosis, treatment planning and for assessing treatment response, as well as providing a practical approach for performing and interpreting multiparametric MRI in the clinical setting. A variety of cases are presented to demonstrate how multiparametric MRI can help differentiate neoplastic from non-neoplastic lesions compared to conventional MRI alone.

Data providers holding sensitive medical data often need to exchange data pertaining to patients for whom they hold particular data. This involves requesting information from other providers to augment the data they hold. However, revealing the superset of identifiers for which a provider requires information can, in itself, leak sensitive private data. Data linkage services exist to facilitate the exchange of anonymized identifiers between data providers. Reliance on third parties to provide these services still raises issues around the trust, privacy and security of such implementations. The rise and use of blockchain and distributed ledger technologies over the last decade has, alongside innovation and disruption in the financial sphere, also brought to the fore and refined the use of associated privacy-preserving cryptographic protocols and techniques. These techniques are now being adopted and used in fields removed from the original financial use cases. In this paper we present a combination of a blockchain-native auditing and trust-enabling environment alongside a query exchange protocol. This allows the exchange of sets of patient identifiers between data providers in such a way that only identifiers lying in the intersection of sets of identifiers are revealed and shared, allowing further secure and privacy-preserving exchange of medical information to be carried out between the two parties. We present the design and implementation of a system demonstrating the effectiveness of these exchange protocols giving a reference architecture for the implementation of such a system.

Objectives To map the Greater Manchester (GM) Child Health Information System network to see if it was a viable source of vaccination data for clinicians working in the PED as a case study.Methods Postprimary care vaccination management systems for GM were visualised using a systems mapping approach, with data obtained from the Office for National Statistics and commissioners in the GM Health and Social Care Partnership.Results Once vaccination data left primary care, it passed through 1 of 10 local child health information services (CHISs), using an assortment of different information technology systems, after which it shed individual identifiers and was aggregated within national systems. None of the existing GM CHISs were accessible to PED practitioners.Conclusion More work needs to be done to explore possible alternative sources of accurate vaccination data during a PED consultation.

Background: The government response to the care failures at the Mid Staffordshire NHS Foundation Trust led to the policy imperative of ‘regular interaction and engagement between nurses and patients’ (Francis R. Report of the Mid Staffordshire NHS Foundation Trust Public Inquiry. London: The Stationery Office; 2013. © Crown copyright 2013. Contains public sector information licensed under the Open Government Licence v3.0) in the NHS. The pressure on nursing to act resulted in the introduction of the US model, known as ‘intentional rounding’, into nursing practice. This is a timed, planned intervention that sets out to address fundamental elements of nursing care by means of a regular bedside ward round. Objectives: The study aims were to examine what it is about intentional rounding in hospital wards that works, for whom and in what circumstances. Design: A multimethod study design was undertaken using realist evaluation methodology. The study was conducted in four phases: (1) theory development; (2) a national survey of all NHS acute trusts in England; (3) in-depth case studies of six wards, involving individual interviews, observations, retrieval of routinely collected ward outcome data and analysis of costs; and (4) synthesis of the study findings. Setting: The study was conducted in acute NHS trusts in England. Participants: A total of 108 acute NHS trusts participated in the survey. Seventeen senior managers, 33 front-line nurses, 28 non-nursing professionals, 34 patients and 28 carers participated in individual interviews. Thirty-nine members of nursing staff were shadowed during their delivery of intentional rounding and the direct care received by 28 patients was observed. Review methods: A realist synthesis was undertaken to identify eight context–mechanism–outcome configurations, which were tested and refined using evidence collected in subsequent research phases. Results: The national survey showed that 97% of NHS trusts had implemented intentional rounding in some way. Data synthesis from survey, observation and interview findings showed that only two of the original eight mechanisms were partially activated (consistency and comprehensiveness, and accountability). The evidence for two mechanisms was inconclusive (visibility of nurses and anticipation); there was minimal evidence for one mechanism (multidisciplinary teamwork and communication) and no evidence for the remaining three (allocated time to care, nurse–patient relationships and communication, and patient empowerment). A total of 240 intentional rounds were observed within 188 hours of care delivery observation. Although 86% of all intentional rounding interactions were observed to be documented, fidelity to the original intervention [i.e. the Studer Group protocol (Studer Group. Best Practices: Sacred Heart Hospital, Pensacola, Florida. Hourly Rounding Supplement. Gulf Breeze, FL: Studer Group; 2007)] was generally low. Limitations: Intentional rounding was often difficult for researchers to observe, as it was rarely delivered as a discrete activity but instead undertaken alongside other nursing activities. Furthermore, a lack of findings about the influence of intentional rounding on patient outcomes in the safety thermometer data limits inferences on how mechanisms link to clinical outcomes for patients. Conclusions: The evidence from this study demonstrates that the effectiveness of intentional rounding, as currently implemented and adapted in England, is very weak and falls short of the theoretically informed mechanisms. There was ambivalence and concern expressed that intentional rounding oversimplifies nursing, privileges a transactional and prescriptive approach over relational nursing care, and prioritises accountability and risk management above individual responsive care. Future work: It is suggested that the insights and messages from this study inform a national conversation about whether or not intentional rounding is the optimum intervention to support the delivery of fundamental nursing care to patients, or if the time is right to shape alternative solutions. Funding: The National Institute for Health Research Health Services and Delivery Research programme.