Exploration of barriers and enablers for evidence-based interventions for upper limb rehabilitation following a stroke : use of Constraint Induced Movement Therapy and Robot Assisted Therapy in NHS Scotland

The routine use of evidence-based upper limb rehabilitation interventions after stroke has the potential to improve function and increase independence. Two such interventions are Constraint Induced Movement Therapy and Robot Assisted Therapy. Despite evidence to support both interventions, their use within the National Health Service appears, anecdotally, to be low. We sought to understand user perceptions in order to explain low uptake in clinical practice. Methods A combination of a cross-sectional online survey with therapists and semi-structured interviews with stroke patients was used to explore uptake and user opinions on the benefits, enablers and barriers to each intervention. Findings The therapists surveyed reported low use of Constraint Induced Movement Therapy and Robot Assisted Therapy in clinical practice within the Scottish National Health Service. Barriers identified by therapists were inadequate staffing, and a lack of training and resources. Interviews with stroke patients identified themes that may help us to understand the acceptability of each intervention, such as the impact of motivation. Conclusion Barriers to the uptake of Constraint Induced Movement Therapy and Robot Assisted Therapy within the clinical setting were found to be similar. Further qualitative research should be completed in order to help us understand the role patient motivation plays in uptake

Annual report 2023 : Sir Jules Thorn Co-Creation Centre in Rehabilitation Technology

The Sir Jules Thorn Centre for Co-Creation of Rehabilitation Technology (CCRT) was set up in early 2021 following a philanthropic award from the Sir Jules Thorn Charitable Trust of £449,000. This allowed two rooms in the Wolfson centre (Biomedical Engineering, University of Strathclyde, Glasgow) to be equipped with state-of-the-art rehabilitation technology (de-weighting systems, neurostimulation, virtual reality, treadmills, bespoke rehab games, communication apps, powered exercise equipment and gamified resistance equipment) and measurement equipment, to add to existing facilities. Following installation of key equipment and ethical approval from the University, the centre commenced recruitment of participants in September 2021. The centre was established as a response to the overwhelming, global, need for rehabilitation (across many conditions) and our universal inability to meet this need. The stated aim of the centre is to lead a multi-faceted rehabilitation revolution by developing a range of cutting-edge technology based on a co-creation approach with users, clinicians and the wider rehabilitation community. The resulting technology and programmes can then be made available in community settings in a cost effective, user friendly way for society-wide benefit. To achieve the aim the team designed an 8-week supervised rehabilitation program located in a gym-like space equipped using a range of integrated technology designed to holistically address the full range of motor and communication impairments caused by stroke. Through this close engagement between technology and users our team of engineers and therapists could create, design and evaluate truly useful rehabilitation technology and develop the necessary protocols around delivering a technology enriched rehabilitation intervention

Can service integration work for universal health coverage? Evidence from around the globe

Universal health coverage (UHC) is at the heart of the new 2030 Agenda for Sustainable Development. Health service integration is seen by World Health Organization as an essential requirement to achieve UHC. However, to date the debate on service integration has focused on perceived benefits rather than empirical impact. We conducted a global review in a systematic manner searching for empirical outcomes of service integration experiments in UHC countries and those on the path to UHC. Sixty-seven articles and reports were found. We grouped results into a unique integration typology with six categories - medical staff from different disciplines; patients and medical staff; care package for one medical condition; care package for two or more medical conditions; specialist stand-alone services with GP services; community locations. We showed that it is possible to integrate services in different human development contexts delivering positive outcomes for patients and clinicians without incurring additional costs. However, the improved outcomes shown were incremental rather than radical and suggest that integration is likely to enhance already well established systems rather than fundamentally changing the outcomes of care

A social identity threat perspective on being the target of generosity from a higher status other

Both giving and receiving money have emotional benefits, but when gifts of value are made in the context of socioeconomic differences, there might also be emotional costs. Four studies (and an internal meta-analysis) tested the idea that receiving a generous gift from someone higher in perceived socioeconomic status (SES) signals social identity threat. In Study 1 (N = 218), participants on average, but especially those with relatively lower SES, reported experiencing more self-conscious negative affect when receiving a generous amount of money (vs. an even split) from a higher status giver in a dictator game. This effect was mediated by feeling pitied by the giver. Studies 2 (N = 331) and 3 (N = 426) revealed similar effects with recalled real-world experiences of receiving a generous gift from higher SES givers. Studies 3 and 4 (N = 142) revealed evidence for serial mediation, with lower relative SES predicting status awareness, status awareness predicting attributions of pity, and attributions of pity in turn predicting self-conscious negative affect. Effects were not significantly moderated by needing or requesting the money, suggesting that acts of generosity across the status divide readily signal social devaluation for those with lower perceived status. Findings have practical and conceptual implications for prosocial giving in a system of social and economic inequality

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)