The visibility of research within mandatory National Health Service Trust Induction programmes in England: An exploratory survey study

Background: Mandatory NHS Trust induction programmes are an integral part of staff orientation processes. Although research is recognised as fundamental to high-quality care, little data exist regarding whether research information is included within hospital induction. Methods: Two online national surveys were developed, with the aim of identifying Trusts which included research within their mandatory induction programme. Survey 1 was distributed to Research and Development managers across England ( n = 201). Survey 2 collated information on the research content and delivery methods of induction material. The work was classified as a service evaluation and reported in accordance with CHERRIES reporting standards. Results: Survey 1 generated 124 unique responses (61% response rate). Thirty-nine percent of Trusts ( n = 48) featured information about research delivery and 24% ( n = 30) about training or support to develop clinical academic careers. There was wide variation in how materials were delivered, by whom and for how long. Conclusions: Currently research has a limited profile within English NHS Trust mandatory induction programmes. This needs to be addressed if research is truly to be considered part of the core National Health Service business. Guidance or a modifiable template could help Trusts communicate about research delivery and clinical academic development and training to all new employees

The visibility of research within mandatory National Health Service Trust Induction programmes in England: an exploratory survey study

Background: Mandatory NHS Trust induction programmes are an integral part of staff orientation processes. Although research is recognised as fundamental to high-quality care, little data exist regarding whether research information is included within hospital induction. Methods: Two online national surveys were developed, with the aim of identifying Trusts which included research within their mandatory induction programme. Survey 1 was distributed to Research and Development managers across England (n = 201). Survey 2 collated information on the research content and delivery methods of induction material. The work was classified as a service evaluation and reported in accordance with CHERRIES reporting standards. Results: Survey 1 generated 124 unique responses (61% response rate). Thirty-nine percent of Trusts (n = 48) featured information about research delivery and 24% (n = 30) about training or support to develop clinical academic careers. There was wide variation in how materials were delivered, by whom and for how long. Conclusions: Currently research has a limited profile within English NHS Trust mandatory induction programmes. This needs to be addressed if research is truly to be considered part of the core National Health Service business. Guidance or a modifiable template could help Trusts communicate about research delivery and clinical academic development and training to all new employees

Social stories in mainstream schools for children with autism spectrum disorder : a feasibility randomised controlled trial

OBJECTIVES: To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. DESIGN: A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. SETTING: 37 primary schools in York, UK. PARTICIPANTS: 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). OUTCOME MEASURES: Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. RESULTS: An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. CONCLUSIONS: Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. TRIAL REGISTRATION NUMBER: ISRCTN96286707; Results

Autism Spectrum Social Stories In Schools Trial (ASSSIST):study protocol for a feasibility randomised controlled trial analysing clinical and cost-effectiveness of Social Stories in mainstream schools

INTRODUCTION: Current evidence suggests that Social Stories can be effective in tackling problem behaviours exhibited by children with autism spectrum disorder. Exploring the meaning of behaviour from a child's perspective allows stories to provide social information that is tailored to their needs. Case reports in children with autism have suggested that these stories can lead to a number of benefits including improvements in social interactions and choice making in educational settings. METHODS AND ANALYSIS: The feasibility of clinical and cost-effectiveness of a Social Stories toolkit will be assessed using a randomised control framework. Participants (n=50) will be randomised to either the Social Stories intervention or a comparator group where they will be read standard stories for an equivalent amount of time. Statistics will be calculated for recruitment rates, follow-up rates and attrition. Economic analysis will determine appropriate measures of generic health and resource use categories for cost-effectiveness analysis. Qualitative analysis will ascertain information on perceptions about the feasibility and acceptability of the intervention. ETHICS AND DISSEMINATION: National Health Service Ethics Approval (NHS; ref 11/YH/0340) for the trial protocol has been obtained along with NHS Research and Development permission from Leeds and York Partnership NHS Foundation Trust. All adverse events will be closely monitored, documented and reported to the study Data Monitoring Ethics Committee. At least one article in a peer reviewed journal will be published and research findings presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN96286707

Blockchain Native Data Linkage

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-02-12, accepted 2021-04-29, epub 2021-10-29Publication status: PublishedData 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

A data-driven, meaningful, easy to interpret, standardised accelerometer outcome variable for global surveillance

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Objectives: Our aim is to demonstrate how a data-driven accelerometer metric, the acceleration above which a person’s most active minutes are accumulated, can a) quantify the prevalence of meeting current physical activity guidelines for global surveillance and b) moving forward, could inform accelerometer-driven physical activity guidelines. Unlike cut-point methods, the metric is population-independent (e.g. age) and potentially comparable across datasets. Design: Cross-sectional, secondary data analysis. Methods: Analyses were carried out on five datasets using wrist-worn accelerometers: children (N=145), adolescent girls (N=1669), office workers (N=114), pre- (N=1218) and post- (N=1316) menopausal women, and adults with type 2 diabetes (N=475). Open-source software (GGIR) was used to generate the magnitude of acceleration above which a person’s most active 60, 30 and 2 minutes are accumulated: M60ACC; M30ACC and M2ACC, respectively. Results: The proportion of participants with M60ACC (children) and M30ACC (adults) values higher than accelerations representative of brisk walking (i.e., moderate-to-vigorous physical activity) ranged from 17-68% in children and 15%-81% in adults, tending to decline with age. The proportion of pre-and postmenopausal women with M2ACC values meeting thresholds for bone health ranged from 6-13%. Conclusions: These metrics can be used for global surveillance of physical activity, including assessing prevalence of meeting current physical activity guidelines. As accelerometer and corresponding health data accumulate it will be possible to interpret the metrics relative to age- and sex- specific norms and derive evidence-based physical activity guidelines directly from accelerometer data for use in future global surveillance. This is where the potential advantages of these metrics lie

Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions.

Conventional genetic testing of individuals with neurodevelopmental presentations and congenital anomalies (ND/CAs), i.e., the analysis of sequence and copy number variants, leaves a substantial proportion of them unexplained. Some of these cases have been shown to result from DNA methylation defects at a single locus (epi-variants), while others can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures). Here, we investigate the clinical diagnostic utility of genome-wide DNA methylation analysis of peripheral blood in unresolved ND/CAs. We generate a computational model enabling concurrent detection of 14 syndromes using DNA methylation data with full accuracy. We demonstrate the ability of this model in resolving 67 individuals with uncertain clinical diagnoses, some of whom had variants of unknown clinical significance (VUS) in the related genes. We show that the provisional diagnoses can be ruled out in many of the case subjects, some of whom are shown by our model to have other diseases initially not considered. By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case subjects with rare epi-variants, a portion of which involved genes clinically or functionally linked to the subjects\u27 phenotypes. This study demonstrates that genomic DNA methylation analysis can facilitate the molecular diagnosis of unresolved clinical cases and highlights the potential value of epigenomic testing in the routine clinical assessment of ND/CAs

BAFopathies\u27 DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations

n/

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin