Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

<b>Background</b> Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.<p></p> <b>Objectives</b> The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.<p></p> <b>Methods</b> A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.<p></p> <b>Discussion</b> The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices

Living with multimorbidity: medical and lay healthcare approaches

Multimorbidity is rapidly becoming the norm rather than the exception in healthcare. Research on this issue is increasing and this review discusses a selection of clinical and social science literature. The focus is on understanding the complexity of the lived experience of multimorbidity and how this is presented in clinical encounters, drawing on examples of arthritis within a multimorbidity context. Taking into account the biophysical, psychological, social and cultural factors that shape multimorbidity this paper calls for a re-conceptualization of the concept, allowing a more dynamic and holistic approach

The implementation of medical revalidation: an assessment using normalisation process theory

Abstract Background Medical revalidation is the process by which all licensed doctors are legally required to demonstrate that they are up to date and fit to practise in order to maintain their licence. Revalidation was introduced in the United Kingdom (UK) in 2012, constituting significant change in the regulation of doctors. The governing body, the General Medical Council (GMC), envisages that revalidation will improve patient care and safety. This potential however is, in part, dependent upon how successfully revalidation is embedded into routine practice. The aim of this study was to use Normalisation Process Theory (NPT) to explore issues contributing to or impeding the implementation of revalidation in practice. Methods We conducted seventy-one interviews with sixty UK policymakers and senior leaders at different points during the development and implementation of revalidation: in 2011 (n = 31), 2013 (n = 26) and 2015 (n = 14). We selected interviewees using purposeful sampling. NPT was used as a framework to enable systematic analysis across the interview sets. Results Initial lack of consensus over revalidation’s purpose, and scepticism about its value, decreased over time as participants recognised the benefits it brought to their practice (coherence category of NPT). Though acceptance increased across time, revalidation was not seen as a legitimate part of their role by all doctors. Key individuals, notably the Responsible Officer (RO), were vital for the successful implementation of revalidation in organisations (cognitive participation category). The ease with which revalidation could be integrated into working practices varied greatly depending on the type of role a doctor held and the organisation they work for and the provision of resources was a significant variable in this (collective action category). Formal evaluation of revalidation in organisations was lacking but informal evaluation was taking place. Revalidation had not yet reached the stage where feedback was being used for improvement (reflexive monitoring category). Conclusions Requiring all organisations to use the same revalidation model made revalidation easy to integrate into existing work for some but problematic for others. In order for revalidation to be fully embedded and successful, impeding factors, such as a lack of resources, need to be addressed

Nuclear matter to strange matter transition in holographic QCD

We construct a simple holographic QCD model to study nuclear matter to strange matter transition. The interaction of dense medium and hadrons is taken care of by imposing the force balancing condition for stable D4/D6/D6 configuration. By considering the intermediate and light flavor branes interacting with baryon vertex homogeneously distributed along R^3 space and requesting the energy minimization, we find that there is a well defined transition density as a function of current quark mass. We also find that as density goes up very high, intermediate (or heavy) and light quarks populate equally as expected from the Pauli principle. In this sense, the effect of the Pauli principle is realized as dynamics of D-branes.Comment: 13 pages, 14 figure

The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis

The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was increased in MS normal-appearing white matter. The mechanism responsible for this increase involved hypomethylation of the promoter region in the PAD 2 gene in MS, but no change (compared to normal) was found in thymus tissue DNA from the same MS patients. In addition, no change was observed in other neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We propose that citrullinated MBP, resulting from elevated levels of PAD 2 represents an important biochemical pathway in the pathogenesis of MS

Three-dimensional kinematic motion analysis of a daily activity drinking from a glass: a pilot study

BACKGROUND: Development of reliable and objective evaluation methods is required, particularly for natural and goal-oriented upper-extremity tasks. Three-dimensional imaging measurement techniques have turned out to be a powerful tool for a quantitative and qualitative assessment of multijoint movements. The purpose of this study was to develop and test a method of three-dimensional motion analysis for the activity "drinking from a glass" and describe the drinking task with kinematic variables in control subjects. METHODS: A protocol was developed for the drinking activity including the set-up of cameras and positions of the markers and the subject. The drinking task included reaching, forward transport with glass, drinking, back transport and returning the hand to the initial position. An optoelectronic system was used for the three-dimensional kinematic motion capture. Movement times, velocities, joint angles and interjoint coordination for shoulder and elbow were computed and analyzed for twenty control subjects. Test-retest consistency was evaluated for six subjects. RESULTS: The test protocol showed good consistency in test-retest. Phase definitions for the drinking task were defined and verified. Descriptive kinematic variables were obtained for movement times, positions, velocities and joint angles for shoulder and elbow joint. Interjoint coordination between shoulder and elbow joint in reaching phase showed a high correlation. CONCLUSION: This study provides a detailed description of the three-dimensional kinematic analysis of the drinking task. Our approach to investigate and analyze a goal-oriented daily activity has a great clinical potential. Consequently, the next step is to use and test this protocol on persons with impairments and disabilities from upper extremities

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses