Exploring the scope for Normalisation Process Theory to help evaluate and understand the processes involved when scaling up integrated models of care: a case study of the scaling up of the Gnosall Memory Service

Purpose: The scaling up of promising, innovative integration projects presents challenges to social and health care systems. Evidence that a new service provides (cost) effective care in a (pilot) locality can often leave us some way from understanding how the innovation worked and what was crucial about the context to achieve the goals evidenced when applied to other localities. Even unpacking the “black box” of the innovation can still leave gaps in understanding with regard to scaling it up. Theory-led approaches are increasingly proposed as a means of helping to address this knowledge gap in understanding implementation. Our particular interest here is exploring the potential use of theory to help with understanding scaling up integration models across sites. The theory under consideration is Normalisation Process Theory (NPT). Design/methodology/approach: The article draws on a natural experiment providing a range of data from two sites working to scale up a well-thought-of, innovative integrated, primary care-based dementia service to other primary care sites. This provided an opportunity to use NPT as a means of framing understanding to explore what the theory adds to considering issues contributing to the success or failure of such a scaling up project. Findings: NPT offers a framework to potentially develop greater consistency in understanding the roll out of models of integrated care. The knowledge gained here and through further application of NPT could be applied to inform evaluation and planning of scaling-up programmes in the future. Research limitations/implications: The research was limited in the data collected from the case study; nevertheless, in the context of an exploration of the use of the theory, the observations provided a practical context in which to begin to examine the usefulness of NPT prior to embarking on its use in more expensive, larger-scale studies. Practical implications: NPT provides a promising framework to better understand the detail of integrated service models from the point of view of what may contribute to their successful scaling up. Social implications: NPT potentially provides a helpful framework to understand and manage efforts to have new integrated service models more widely adopted in practice and to help ensure that models which are effective in the small scale develop effectively when scaled up. Originality/value: This paper examines the use of NPT as a theory to guide understanding of scaling up promising innovative integration service models

Multidisciplinary group performance—measuring integration intensity in the context of the North West London Integrated Care Pilot

Introduction: Multidisciplinary Group meetings (MDGs) are seen as key facilitators of integration, moving from individual to multidisciplinary decision-making, and from a focus on individual patients to a focus on patient groups. We have developed a method for coding MDG transcripts to identify whether they are or are not vehicles for delivering the anticipated efficiency improvements across various providers and apply it to a test case in the North West London Integrated Care Pilot. Methods: We defined ‘integrating’ as the process within the MDG meeting that enables or promotes an improved collaboration, improved understanding, and improved awareness of self and others within the local healthcare economy such that efficiency improvements could be identified and action taken. Utterances within the MDGs are coded according to three distinct domains grounded in concepts from communication, group decision-making, and integrated care literatures—the Valence, the Focus, and the Level. Standardized weighted integrative intensity scores are calculated across ten time deciles in the Case Discussion providing a graphical representation of its integrative intensity. Results: Intra- and Inter-rater reliability of the coding scheme was very good as measured by the Prevalence and Bias-adjusted Kappa Score. Standardized Weighted Integrative Intensity graph mirrored closely the verbatim transcript and is a convenient representation of complex communication dynamics. Trend in integrative intensity can be calculated and the characteristics of the MDG can be pragmatically described. Conclusion: This is a novel and potentially useful method for researchers, managers and practitioners to better understand MDG dynamics and to identify whether participants are integrating. The degree to which participants use MDG meetings to develop an integrated way of working is likely to require management, leadership and shared values

Psychometric Properties of the Dutch Contextual Assessment of Social Skills (CASS):An Independent Observational Outcome Measure of Social Skills in Autistic Adolescents

The goal of this study was to translate and adapt the original 9-item of the Contextual Assessment of Social Skills (CASS) to a Dutch version and assess its psychometric qualities. Autistic adolescents aged 12 to 18 years (n = 99) took part in a randomized controlled trial. In this study, pre-intervention data were utilized. The original CASS was adapted to ensure cultural relevance and the content validity was assessed. Data was used to assess reliability and structural validity, using confirmatory factor analysis. 4-item were added to the CASS during the adaptation to better align with the objectives of the experimental intervention. The original 9-item had inter-item correlations between.01 and.70. The Cronbach’s alpha for the original 4-item total score was moderate (α =.69), while for a 7-item total score, it was high (α =.86). This 7-item total score had a sufficient model fit (Comparative Fit Index =.90). This total score had a significant correlation with the Assertion subscale of the Social Skills Improvement System-Adolescent (SSIS-A) (r = 0.26, p &lt;.01), and the Social Responsiveness Scale-2 (SRS-2) total score (r = − .21, p =.04) indicating sufficient convergent validity. The CASS total score was not correlated with the Repetitive and Restricted Behavior scale of the SRS-2 (r = − .08, p =.43), indicating sufficient divergent validity. The Dutch CASS can be considered a conceptually sound and reliable observational instrument for assessing social conversational skills in Dutch autistic youth. Further evaluation of its feasibility when implemented in practice, outside of clinical research, is needed. Trial registration: Dutch trail register NTR6255 (NL6117) 08/02/2017 https://www.trialregister.nl/trial/6117.</p

Unique Co‐Catalytic Behavior of Protic Ionic Liquids as Multifunctional Electrolytes for Water Splitting

Hydrogen production from water splitting holds great promise for solving today’s energy crisis but it is challenging to have high efficiency and low cost. For the first time, a protic ionic liquid (PIL), diethylammonium formate (DEAF) was used as a multifunctional electrolyte in water splitting, demonstrating a unique role of co‐catalyst for the hydrogen evolution reaction (HER) with the highest current density (21 mA cm−2 at −0.5 V) and the most positive onset potential (−0.002 V) in comparison to aprotic ILs and commonly used inorganic salts. Moreover, the concentration of PIL and temperature of electrolyte solution were optimized. The possible mechanism for the multifunctionality and high performance for water splitting using this PIL was proposed using X‐ray photoelectron spectroscopy (XPS). The high performance for HER, simplicity and low cost for synthesis, and unique properties make DEAF highly promising as an electrolyte toward water splitting.DEAFening: For the first time, a protic ionic liquid, diethylammonium format, is used as a multifunctional electrolyte in a water‐splitting cell, demonstrating a unique role as co‐catalyst.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137194/1/celc201500458.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137194/2/celc201500458-sup-0001-misc_information.pd

Genome-wide mouse embryonic stem cell regulatory network self-organisation : a big data CoSMoS computational modelling approach.

The principal barrier to gaining understanding of embryonic stem (ES) cell regulatory networks is their complexity. Reductionist approaches overlook much of the complexity inherent in these networks and treat the ES cell regulatory system as more or less equivalent to the sum of its component parts, studying them in relative isolation. However, as we learn more about regulatory components it becomes increasingly difficult to integrate complex layers of knowledge and to develop more refined understanding. We seek better control of the complexity inherent in non-equilibrium ES cell regulatory networks undergoing lineage specification by developing computer simulations of self-organisation using the CoSMoS approach. Simulation, together with the hypothesis that lineage computation occurs at the edge of chaos, should allow us to investigate the driving of gradual accumulation of network complexity 'from the bottom up'. Here, we present the first step in this design process: use of the CoSMoS approach to develop a highly abstracted model and simulation of regulatory network activity driven by just single pluripotent transcription factors (TF), but at genome-wide scales. We investigate three TFs in isolation: Oct4, Nanog and Sox2, central elements of the core pluripotent network of mouse embryonic stem cells. This provides a suitable basis for future modelling of multiple interacting TFs

Review of evidence for the alignment of guidelines on Aboriginal and Torres Strait Islander absolute cardiovascular disease risk: A report prepared for the Australian Government Department of Health

Policy context: Cardiovascular disease (CVD) is highly preventable. CVD continues to be the largest contributor to mortality within the Aboriginal and Torres Strait Islander population and rates of CVD are disproportionately higher within the Australian Aboriginal and Torres Strait Islander population compared to the non-Indigenous population. Improving uptake of current evidence based solutions such as the absolute risk approach to CVD within the Aboriginal and Torres Strait Islander population is important to address this disparity. Although there are several tools available supporting an absolute CVD risk approach, clinical uptake is limited due to a number of factors including an outdated continued reliance on the ‘single risk factor’ approach to prevention, diagnosis and treatment of CVD. A major barrier to uptake is inconsistent messages in the current clinical practice guidelines. Key messages: There are three main guidelines on the absolute CVD risk approach for Aboriginal and Torres Strait Islander peoples in Australia: The NVDPA Guidelines for the Management of Absolute Cardiovascular Disease Risk; The Central Australian Rural Practitioners Association Standard Treatment Manual; and the RACGP National Guide to a Preventive Health Assessment for Aboriginal and Torres Strait Islander People. There is considerable alignment between the existing guidelines, including the need for an absolute risk approach, conditions conferring automatic high risk, use of the Framingham risk equation as the basis of calculating absolute risk, and the need to treat people at a greater than 15% risk of a primary CVD event over the next five years. The guidelines diverge materially in relation to four recommendations: 1) the age at which to commence absolute CVD risk assessment; 2) whether or not calculated risk scores should be adjusted upward by 5%; 3) how often CVD risk should be assessed; and 4) treatment targets for blood pressure. Available evidence indicates that CVD events and high absolute CVD risk occurs earlier in Aboriginal and Torres Strait Islander peoples, and that prevention of CVD should also start early. The proportion of Aboriginal and Torres Strait Islander peoples at high absolute CVD risk at the ages of 18-34 years broadly corresponds to the proportion at high risk among the general population aged 45-54 years. Limited evidence suggests that the current risk scores are likely to underestimate risk in Aboriginal and Torres Strait Islander peoples. Specific data on the extent of underestimation and alternative validated risk scores in this population are lacking. There is no primary data on adjusting risk scores upwards by 5% in Aboriginal and Torres Strait Islander people. Frequency of CVD risk assessment should be based on initial level of risk but the optimal interval for risk reassessment at each level of risk is not clear. There is general agreement between the guidelines to lower blood pressure as tolerated but there are inconsistencies in the exact blood pressure target. Evidence suggests that reductions in systolic blood pressure result in proportional reductions in CVD events and all-cause mortality. CVD guidelines could be kept up to date by adopting a ‘living’ guidelines model, but consideration needs to be given to how to identify relevant updated evidence and how to integrate the updates into electronic decision support tools.This research was supported by a grant from the Australian Government Department of Health

Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia

Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p&lt;0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p&lt;0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p&lt;0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Modelling clinical narrative as computable knowledge: The NICE computable implementation guidance project

Introduction: Translating narrative clinical guidelines to computable knowledge is a long‐standing challenge that has seen a diverse range of approaches. The UK National Institute for Health and Care Excellence (NICE) Content Advisory Board (CAB) aims ultimately to (1) guide clinical decision support and other software developers to increase traceability, fidelity and consistency in supporting clinical use of NICE recommendations, (2) guide local practice audit and intervention to reduce unwarranted variation, (3) provide feedback to NICE on how future recommendations should be developed. Objectives: The first phase of work was to explore a range of technical approaches to transition NICE toward the production of natively digital content. Methods: Following an initial ‘collaborathon’ in November 2022, the NICE Computable Implementation Guidance project (NCIG) was established. We held a series of workstream calls approximately fortnightly, focusing on (1) user stories and trigger events, (2) information model and definitions, (3) horizon‐scanning and output format. A second collaborathon was held in March 2023 to consolidate progress across the workstreams and agree residual actions to complete. Results: While we initially focussed on technical implementation standards, we decided that an intermediate logical model was a more achievable first step in the journey from narrative to fully computable representation. NCIG adopted the WHO Digital Adaptation Kit (DAK) as a technology‐agnostic method to model user scenarios, personae, processes and workflow, core data elements and decision‐support logic. Further work will address indicators, such as prescribing compliance, and implementation in document templates for primary care patient record systems. Conclusions: The project has shown that the WHO DAK, with some modification, is a promising approach to build technology‐neutral logical specifications of NICE recommendations. Implementation of concurrent computable modelling by multidisciplinary teams during guideline development poses methodological and cultural questions that are complex but tractable given suitable will and leadership

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy International Clinical Practice Guideline Based on Systematic Reviews:International Clinical Practice Guideline Based on Systematic Reviews

IMPORTANCE: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. OBJECTIVE: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. EVIDENCE REVIEW: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. FINDINGS: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). CONCLUSIONS AND RELEVANCE: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline