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Background/aim: In 2018, the European Medicines Agency strengthened warnings in relation to fluoroquinolone (FQ)-associated tendon injury. There is a lack of published data on FQs and tendon injury in an Irish context. The aim of the study was to investigate incidents and claims relating to FQs and tendon injury through an analysis of National Incident Management System (NIMS) data., Methods: The NIMS database was searched for incidents created between 1st June 2018 and 31st May 2023 which involved any FQ and referenced tendon injury. The incident data was analysed under predetermined field headings. NIMS was also searched for clinical claims involving any FQ with a Claim Finalised Date between 1st June 2018 and 31st May 2023. The claims were analysed to identify common themes., Results: The study identified 20 incidents which related to FQs and tendon injury, although only six reported an actual tendon injury. In 15 (75%) of the incidents, the prescription of a FQ was deemed inappropriate by the reporter. The study found four finalised claims, all of which related to bilateral Achilles tendon rupture following FQ exposure. In all four cases, the patient was aged over 60 and the injury occurred within days of commencing treatment., Conclusions: This study confirms that FQs continue to be prescribed inappropriately in high-risk patients and that incidents of tendon injury following FQ exposure continue to occur despite regulatory moves of raise awareness of this issue. Additional measures to minimise the risk of avoidable patient harm may be warranted., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Attempting to improve emergency care (EC) advanced clinical practitioner (ACP) training, Health Education England (HEE) South West (SW) implemented a pilot, whereby emergency departments (ED) were provided with enhanced funding and support to help ED consultants deliver teaching and supervision to EC ACPs to ensure more timely completion of EC ACP training compared with previous cohorts training in the region.We explored the experiences of trainee EC ACPs and consultant EC ACP leads working in EDs, which had implemented the new regional pilot., Methods: We used a qualitative design to conduct semi-structured interviews with trainee EC ACPs and consultant EC ACP leads across five EDs that had implemented the HEE SW pilot. Interview data were analysed thematically., Results: Twenty-five people were interviewed. We identified four themes: (1) the master's in advanced practice could be better aligned with the Royal College of Emergency Medicine credentialling e-portfolio; (2) EC ACP training needs some flexibility to reflect the individual-'one size does not fit all'; (3) supervision and teaching were recognised as important but requires significant staff capacity that is impacted by external pressures and (4) unclear role expectations and responsibilities hinder role transition and impact role identity.It was notable that EC ACPs primarily spoke about the development of their clinical skills both academically and within the workplace, despite there being other skills mentioned in the multiprofessional framework for advanced practice (leadership and management, education and research)., Conclusion: A clear supervision structure with protected time allocated for teaching and assessment of clinical skills within the ED is essential to facilitate trainee EC ACP progression. However, increasing demands on EDs make this a challenging goal to achieve. Role identity issues continue to persist despite the introduction of new guidance designed to provide more clarity around the ACP role., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Lay Abstract: Autistic play is generally described from a deficit perspective where the players themselves have been overlooked. It is important to consult with autistic children themselves about their understanding of play. We asked autistic children about their views on play using many different creative ways that were chosen by the children themselves. We analysed findings using reflexive thematic analysis. Autistic children in this research described play as involving feelings and emotions of pleasure and joy, autonomy and agency, playing by themselves and with others and engagement with materials and activities as meaningful. It is very important that we ask the players themselves what they think about play rather than relying on deficit framed, non-autistic definitions of autistic play. In this article, we will discuss how these findings will help develop future research, theory and practice in respecting children's right to authentic play experiences., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The opioid crisis has claimed approximately one million lives in the United States since 1999, underscoring a significant public health concern. This surge in opioid use disorder (OUD) fatalities necessitates improved therapeutic options. Current OUD therapies often require daily clinical visits, leading to poor patient compliance and high costs to the health systems. Levo-alpha-acetylmethadol (LAAM) is a long-lasting OUD drug, and the thrice-weekly oral LAAM solution can offer better patient compliance compared to the traditional daily methadone therapies. However, LAAM is FDA-approved but withdrawn from the market. As part of the NIH HEAL Initiative, we aim to reintroduce LAAM back to the market to improve OUD therapeutic options by developing a novel Janus LAAM-loaded fibrous buccal film (LFBF) formulation made of a drug-containing electrospun fibrous layer and a backing layer. The buccal administration of LFBF exhibited superior transmucosal delivery of LAAM to systemic circulation with a nearly 4-fold higher drug bioavailability than the conventional oral LAAM solution in rabbits. Furthermore, upon buccal administration in an opioid-dependent rat model, the LFBF significantly decreased fentanyl choice in the fentanyl-dependent rats, while the conventional oral LAAM solution did not at the same dose. Both the buccal film and oral solution of LAAM reduced somatic withdrawal signs in the experimental animals. These findings highlight the buccal delivery of LAAM using electrospun fibers as a promising strategy with improved drug bioavailability. Furthermore, it sheds light on future clinical applications aiming for enhanced treatment outcomes in the battle against the current opioid crisis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qingguo Xu has patent #WO2023225630A2 (Formulations for administering LAAM, norLAAM and dinorLAAM and methods of their use to treat opioid use disorder) pending to Virginia Commonwealth University. Hadi Sudarjat has patent #WO2023225630A2 (Formulations for administering LAAM, norLAAM and dinorLAAM and methods of their use to treat opioid use disorder) pending to Virginia Commonwealth University. Aji Alex Moothedathu Raynold has patent #WO2023225630A2 (Formulations for administering LAAM, norLAAM and dinorLAAM and methods of their use to treat opioid use disorder) pending to Virginia Commonwealth University. Xiuling Lu has patent #WO2023225630A2 (Formulations for administering LAAM, norLAAM and dinorLAAM and methods of their use to treat opioid use disorder) pending to Virginia Commonwealth University. Charles OKeeffe has patent #WO2023225630A2 (Formulations for administering LAAM, norLAAM and dinorLAAM and methods of their use to treat opioid use disorder) pending to Virginia Commonwealth University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study investigated relationships between thin mental boundary functioning, creativity, imaginary companions (ICs), and anomalous '(entity) encounter experiences.' A convenience sample of 389 respondents completed the Revised Transliminality Scale, Oxford-Liverpool Inventory of Feelings and Experiences, Creative Experiences Questionnaire, Survey of Strange Events, and a measure of Childhood Imaginary Companions. Competing testing with path analysis found that the best-fitting model was consistent with the causal chain of 'Thin Boundaries (transliminality and schizotypy) → Creative Experiences → ICs → (Entity) Encounter Experiences.' These results suggest that deep-types of ICs (i.e., showing apparent independent agency) are perhaps most accurately characterized as syncretic cognitions versus hallucination-like experiences. The authors examine these findings relative to study limitations, as well as discussing the need for future research that approaches ICs as a special mental state that can facilitate allied altered-anomalous experiences. In this context, this study furthered understanding of relationships between conscious states related to mental boundaries, childhood imaginary companions, creative experiences, and entity encounters., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The material properties of individual micro-struts are critical to the overall success of lattice structures. These properties can be significantly compromised by defects inherited from powder bed fusion processes. Among these defects, porous inclusions are well understood to have a detrimental effect on mechanical properties; posing a high risk to the implant under loading. While the majority of these defects can be avoided through optimisation of printing parameters, this has generally only been done for traditional bulk components with no in-designed porosity. Furthermore, a number of studies have observed changes in the frequency of such porous inclusions as feature size is reduced, indicating a size effect. This also suggests that the optimal parameters for bulk material are not necessarily translatable to the individual micro-struts which build the lattice. In this study, the relationship between parameter optimisation and feature size was investigated. Here, a higher energy density input was required for processing micro-strut lattices with an optimised relative density, than it was for bulk components. This could be attributed to faster rates of heat loss in micro-strut samples on account of their increased surface-to-volume ratio. The consequential improvement in mechanical properties was also assessed. An increase in both strength and stiffness could be largely attributed to an increase in the percentage volume of load bearing material, while improvements in failure strain were largely driven by minimisation of stress concentrations around the irregular pore morphologies. Fatigue properties did not improve beyond the effects of yielding. Rather, crack initiation was dominated by surface defects; which on account of their surface free energy, experience a much higher stress intensity factor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Emergency doctors routinely face uncertainty-they work with limited patient information, under tight time constraints and receive minimal post-discharge feedback. While higher uncertainty tolerance (UT) among staff is linked with reduced resource use and improved well-being in various specialties, its impact in emergency settings is underexplored. We aimed to develop a UT measure and assess associations with doctor-related factors (eg, experience), patient outcomes (eg, reattendance) and resource use (eg, episode costs)., Methods: From May 2021 to February 2022, emergency doctors (specialty trainee 3 and above) from five Yorkshire (UK) departments completed an online questionnaire. This included a novel UT measure-an adapted Physicians' Reaction to Uncertainty scale collaboratively modified within our team according to Hillen et al 's (2017) UT model. The questionnaire also included well-being-related measures (eg, Brief Resilience Scale) and assessed factors like doctors' seniority. Patient encounters involving prespecified 'uncertainty-inducing' problems (eg, headache) were analysed. Multilevel regression explored associations between doctor-level factors, resource use and patient outcomes., Results: 39 doctors were matched with 384 patients. The UT measure demonstrated high reliability (Cronbach's α =0.92) and higher UT was significantly associated with better psychological well-being including greater resilience (Pearson's r=0.56; 95% CI=0.30 to 0.74) and lower burnout (eg, Cohen's d=-2.98; -4.62 to -1.33; mean UT difference for 'no' vs 'moderate/high' burnout). UT was not significantly associated with resource use (eg, episode costs: β=-0.07; -0.32 to 0.18) or patient outcomes including 30-day readmission (eg, OR=0.82; 0.28 to 2.35)., Conclusions: We developed a reliable UT measure for emergency medicine. While higher UT was linked to doctor well-being, its impact on resource use and patient outcomes remains unclear. Further measure validation and additional research including intervention trials are necessary to confirm these findings and explore the implications of UT in emergency practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: This scoping review aims to map and examine the extent and type of available evidence on health professionals' education accreditation within Africa., Introduction: The demand for health professionals is unprecedentedly high globally. One response to this challenge has been expanding training through more liberal education policies, facilitating private sector participation in education service provision. Some evidence suggests that this is a double-edged sword, increasing quantity but compromising the quality of health professionals produced. Regulation can provide a framework to assure and continuously improve quality, with such regulation in place in 79% of World Health Organization African countries. However, it is unclear how much and what evidence has been generated on how accreditation happens, where it is concentrated, and the prevailing evidence gaps within this region; therefore, we propose to conduct a scoping review., Inclusion Criteria: This review will include articles and dissertations focusing on the accreditation of health professionals' education in Africa. All methodological approaches and designs will be included. Conference abstracts and protocols will be excluded., Methods: This review will be carried out according to the JBI scoping review methodology. We conducted an initial search of CINAHL and MEDLINE to identify relevant articles. This informed our selection of keywords, along with index terms, to create a comprehensive search strategy for CINAHL (EBSCOhost), MEDLINE (Ovid), Global Health (Ovid), ERIC (EBSCOhost), Web of Science Core Collection, Embase, and Scopus. Sources included will be limited to those published starting from 2000 onwards. Data will be presented using tables and charts, accompanied by a narrative summary., Detail of This Review Project Can Be Found in Open Science Framework: https://doi.org/10.17605/OSF.IO/W5G7T., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on Behalf of JBI.)

Objective: Learning from adverse outcomes in health and social care is critical to advancing a culture of patient safety and reducing the likelihood of future preventable harm to service users. This review aims to present an overview of all clinical claims finalised in one calendar year involving publicly funded health and social care providers in Ireland., Design: This is a retrospective observational study. The Clinical Risk Unit (CRU) of the State Claims Agency identified all service-user clinical claims finalised between 1 January 2017 and 31 December 2017 from Ireland's National Incident Management System (n=713). Claims that had incurred financial damages were considered for further analysis (n=356). 202 claims underwent an in-depth qualitative review. Of these, 57 related to maternity and gynaecology, 64 to surgery, 46 to medicine, 20 to community health and social care and 15 related to children's healthcare., Results: The services of surgery and medicine ranked first and second, respectively, in terms of a number of claims. Claims in maternity services, despite ranking third in terms of claims numbers, resulted in the highest claims costs. Catastrophic injuries in babies resulting in cerebral palsy or other brain injury accounted for the majority of this cost.Diagnostic errors and inadequate or substandard communication, either with service users and/or interprofessional communication with colleagues, emerged as common issues across all clinical areas analysed. Quantitative analysis of contributory factors demonstrated that the complexity and seriousness of the service user's condition was a significant contributory factor in the occurrence of incidents leading to claims., Conclusion: This national report identifies common issues resulting in claims. Targeting these issues could mitigate patient safety risks and reduce the cost of claims., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Porous titanium scaffolds fabricated by powder bed fusion additive manufacturing techniques have been widely adopted for orthopedic and bone tissue engineering applications. Despite the many advantages of this approach, topological defects inherited from the fabrication process are well understood to negatively affect mechanical properties and pose a high risk if dislodged after implantation. Consequently, there is a need for further post-process surface cleaning. Traditional techniques such as grinding or polishing are not suited to lattice structures, due to lack of a line of sight to internal features. Chemical etching is a promising alternative; however, it remains unclear if changes to surface properties associated with such protocols will influence how cells respond to the material surface. In this study, we explored the response of bone marrow derived mesenchymal stem/stromal cells (MSCs) to Ti-6Al-4V whose surface was exposed to different durations of chemical etching. Cell morphology was influenced by local topological features inherited from the SLM fabrication process. On the as-built surface, topological nonhomogeneities such as partially adhered powder drove a stretched anisotropic cellular morphology, with large areas of the cell suspended across the nonhomogeneous powder interface. As the etching process was continued, surface defects were gradually removed, and cell morphology appeared more isotropic and was suggestive of MSC differentiation along an osteoblastic-lineage. This was accompanied by more extensive mineralization, indicative of progression along an osteogenic pathway. These findings point to the benefit of post-process chemical etching of additively manufactured Ti-6Al-4V biomaterials targeting orthopedic applications., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Background: Thoracolumbar transcutaneous spinal cord stimulation (tSCS) non-invasively evokes posterior root-muscle reflexes (PRMR) with the aim of neuromodulating sensorimotor function following spinal cord injury. Research is still in its infancy regarding the effect of body position on the nature of these spinally evoked responses. Therefore, the aim of this study was to investigate the influence of body position on the nature of PRMR responses during tSCS. Methods: A total of 11 (6M, 5F) participants completed a full PRMR recruitment curve from 10 ma up to 120 ma (10 ma increments) at the T11/12 intervertebral space using a singular 3.2 cm diameter cathode. At each intensity, three paired pulses (50 ms inter-pulse interval), followed by three singular pulses with a six-second delay were applied in each body position (supine, supine 90-90, sitting and standing) in a randomised order. The PRMR responses in lower limb muscles were recorded using wireless electromyographic sensors placed on the Soleus , Tibialis Anterior , Rectus Femoris and Bicep Femoris long head. A two-way (body position × muscle) repeated measures analysis of variance was used to investigate the effect of body position on PRMR-evoked responses. Results: There was a significant main effect of body position on PRMR resting motor threshold (RMT) ( p < 0.001), first response peak-to-peak amplitude ( p = 0.003) and percentage post-activation depression (%PAD) ( p = 0.012). Sitting had significantly higher RMT and significantly lower first response peak-to-peak amplitudes compared to all other positions, but significant differences in %PAD were only detectible between supine and standing. Conclusions: Body position influences the nature of PRMR-evoked responses during tSCS.

The NHS 111 service triages over 16,650,745 calls per year and approximately 48% of callers are triaged to a primary care disposition, such as a telephone appointment with a general practitioner (GP). However, there has been little assessment of the ability of primary care services to meet this demand. If a timely service cannot be provided to patients, it could result in patients calling 999 or attending emergency departments (ED) instead. This study aimed to explore the patient journey for callers who were triaged to a primary care disposition, and the ability of primary care services to meet this demand. We obtained routine, retrospective data from the Connected Yorkshire research database, and identified all 111 calls between the 1st January 2021 and 31st December 2021 for callers registered with a GP in the Bradford or Airedale region of West Yorkshire, who were triaged to a primary care disposition. Subsequent healthcare system access (111, 999, primary and secondary care) in the 72 hours following the index 111 call was identified, and a descriptive analysis of the healthcare trajectory of patients was undertaken. There were 56,102 index 111 calls, and a primary care service was the first interaction in 26,690/56,102 (47.6%) of cases, with 15,470/26,690 (58%) commenced within the specified triage time frame. Calls to 999 were higher in the cohort who had no prior contact with primary care (58% vs 42%) as were ED attendances (58.2% vs 41.8), although the proportion of avoidable ED attendances was similar (10.5% vs 11.8%). Less than half of 111 callers triaged to a primary care disposition make contact with a primary care service, and even when they do, call triage time frames are frequently not met, suggesting that current primary care provision cannot meet the demand from 111., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pilbery et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Long waiting times in the ED have been shown to cause negative outcomes for patients. This study aims to assess the effect in reducing length of stay of (1) preventing low-acuity attenders from attending the ED and (2) diverting low-acuity attenders at triage to a colocated general practice (GP) service., Methods: Discrete event simulation was used to model a large urban teaching hospital in the UK, as a case study, with a colocated GP service. The Centre for Urgent and Emergency Care research database patient-level database (May 2015-April 2016), secondary literature and expert elicitation were used to inform the model. The model predicted length of stay, the percentage of patients being seen within 4 hours and the incremental cost-effectiveness of the colocated GP service., Results: The model predicted that diverting low-acuity patients to a colocated GP open 9:00 to 17:00 reduces the average time in the system for higher acuity attenders by 29 min at an estimated additional cost of £6.76 per patient on average. The percentage of higher acuity patients being seen within 4 hours increased from 61% to 67% due to the reduction in the length of stay of those who were in the ED for the longest time. However, the model is sensitive to changes in model inputs and there is uncertainty around ED activity durations, for which further primary data collection would be useful., Conclusion: Reducing the proportion of low-acuity attenders at the ED could have an impact on the time in the ED for higher acuity patients due to their use of shared resources, but is insufficient alone to meet current targets. The simulation model could be adapted for further analyses to understand which other changes would be needed to meet current government targets., Competing Interests: Competing interests: SC is an Emergency Medicine Expert Adviser for the Welsh and English Ombudsman., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The Sit-to-Stand (STS) transition is one of the most used activities of daily living and vital for independence. Neurological, or physical injuries impairing functional mobility or sensory feedback often require rehabilitative programs or therapeutic interventions. Understanding the biomechanical elements of daily movements and the interaction between these elements may help inform rehabilitation protocols and optimize targeted interventions, such as stimulation protocols., Research Question: What are the effects of different initial knee angle, arm facilitation and proprioceptive input on leg muscle activation patterns and balance during and after a sit-to-stand?, Methods: EMG of four lower limb muscles were recorded in 20 healthy participants as well centre-of-pressure sway amplitude and velocity, as participants stood from a seated position. Initial knee angles were set to various levels of extension (80°, 90°, 100°) and surface stability and arm facilitation were altered using a foam mat or crossing arms. Data were analysed across 3 phases of the STS transition., Results: More extended knee angles resulted in greater mediolateral sway during each phase (p < .01) and had a detrimental effect on anterior-posterior sway in phases 1 and 3. EMG data suggested more extended initial knee angles also increased EMG activity of the Tibialis Anterior (p < .001) and Bicep Femoris (p < .02) within Phases 1 and 2 to assist lift and stabilisation., Significance: Findings of this study outline phase-based muscle involvement as well as the compounding effects of reduced proprioceptive input and knee angle, on difficulty of the STS transition. Such results emphasising the need to take sensory and mobility issues into consideration when designing rehabilitative programs or stimulation control systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Covid-19 crisis sparked service reconfigurations in healthcare systems worldwide. With postgraduate medical education sitting within these systems, service reconfigurations substantially impact trainees and their training environment. This study aims to provide an in-depth qualitative understanding of the impact of service reconfiguration on doctors' training during the pandemic, identifying opportunities for the future as well as factors that pose risks to education and training and how these might be mitigated., Methods: Qualitative parallel multi-centre case studies examined three Trusts/Health Boards in two countries in the United Kingdom. Data were collected from online focus groups and interviews with trainees and supervisors using semi-structured interview guides (September to December 2020). A socio-cultural model of workplace learning, the expansive-restrictive continuum, informed data gathering, analysis of focus groups and coding., Results: Sixty-six doctors participated, representing 25 specialties/subspecialties. Thirty-four participants were male, 26 were supervisors, 17 were specialty trainees and 23 were foundation doctors. Four themes described the impact of pandemic-related service reconfigurations on training: (1) Development of skills and job design, (2) Supervision and assessments, (3) Teamwork and communication, and (4) Workload and wellbeing. Service changes were found to both facilitate and hinder education and training, varying across sites, specialties, and trainees' grades. Trainees' jobs were redesigned extensively, and many trainees were redeployed to specialties requiring extra workforce during the pandemic., Conclusions: The rapid and unplanned service reconfigurations during the pandemic caused unique challenges and opportunities to doctors' training. This impaired trainees' development in their specialty of interest, but also presented new opportunities such as cross-boundary working and networking., (© 2023. The Author(s).)

Background: People with serious mental illness experience worse physical health and greater mortality than the general population. Crude rates of A&E attendance and acute hospital admission are higher in people with serious mental illness than other hospital users. We aimed to further these findings by undertaking a standardised comparison of urgent and emergency care pathway use among users of mental health services and the general population., Methods: Retrospective cohort analysis using routine data from 2013-2016 from the CUREd dataset for urgent and emergency care contacts (NHS 111, ambulance, A&E and acute admissions) and linked mental health trust data for Sheffield, England. We compared annual age- and sex-standardised usage rates for each urgent and emergency care service between users of mental health services and those without a recent history of mental health service use., Results: We found marked differences in usage rates for all four urgent and emergency care services between the general population and users of mental health services. Usage rates and the proportion of users were 5-6 times and 3-4 times higher in users of mental health services, respectively, for all urgent and emergency care services. Users of mental health services were often more likely to experience the highest or lowest acuity usage characteristics., Conclusions: Current users of mental health services were heavily over-represented among urgent and emergency care users, and they made more contacts per-person. Higher service use among users of mental health services could be addressed by improved community care, more integrated physical and mental health support, and more proactive primary care. A complex pattern of service use among users of mental health services suggests this will need careful targeting to reduce avoidable contacts and optimise patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lewis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Medication adherence impacts health outcomes. Healthcare organisations implementing system-level interventions have potential for greater spread and sustainability than individual-level interventions. Within the integrated US Veterans Health Administration, a multidisciplinary team developed and evaluated a pilot quality improvement programme to assess the feasibility of automatic mailed prescription refills for patients with diabetes and low medication adherence (assessed by medication possession ratio <80%)., Methods: Patients were randomised to usual care with self-initiated refills versus automatic mailed refills for 6 months. Process outcomes included glycaemic control measures (HgbA1C), medication possession ratios for both automatic and self-initiated (reference) refills of medications, patient satisfaction and workforce effort (pharmacist time)., Results: Overall, 199 patients were randomised to automatic refills (n=99; 40 of whom participated) versus usual care (n=100). In multivariable analysis adjusting for baseline differences, after 6 months there was no difference in the proportion of patients with follow-up HgbA1C <8% (60.8% automatic refills vs 60.5% usual care, p=0.96). In the automatic refill group, the medication possession ratio for reference medicines was significantly higher than usual care (63.9% vs 54.5%, 95% CI (for difference) 3.1% to 15.9%, p<0.01)., Conclusions: Implications and lessons from this pilot programme include potential beneficial indirect effects from automatic medication refills on patient self-initiated refills of other medications; the importance of tailoring solutions to patient subgroups and specific adherence barriers; and recognition that the rapid deployment, iteration and evaluation of the project was facilitated by a multidisciplinary team embedded within an organisational learning health system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Transcutaneous spinal cord stimulation (tSCS) at the cervical level may facilitate improved upper-limb function in those with incomplete tetraplegia. While clinical trials are ongoing, there is still much debate regarding the transmission pathway as well as appropriate stimulation parameters. This study aimed to explore the extent to which cervical tSCS can induce mono-synaptic reflexes in discrete upper-limb motor pools and examine the effects of altering stimulus location and intensity., Methods: Fourteen participants with intact nervous systems completed two laboratory visits, during which posterior root-muscle reflexes (PRMRs) were evoked via a 3 × 3 cathode matrix applied over the cervical spine. An incremental recruitment curve at the C7 vertebral level was initially performed to attain resting motor threshold (RMT) in each muscle. Paired pulses (1 ms square monophasic with inter-pulse interval of 50 ms) were subsequently delivered at a frequency of 0.25 Hz at two intensities (RMT and RMT + 20%) across all nine cathode positions. Evoked responses to the 1st (PRMR 1 ) and 2nd (PRMR 2 ) stimuli were recorded in four upper-limb muscles., Results: A significant effect of the spinal level was observed in all muscles for PRMR 1 , with greater responses being recorded caudally. Contralateral stimulation significantly increased PRMR 1 in Biceps Brachii ( p < 0.05, F = 4.9, η2 = 0.29), Flexor Carpi Radialis ( p < 0.05, F = 4.9, η2 = 0.28) and Abductor Pollicis Brevis ( p < 0.01, F = 8.9, η2 = 0.89). Post-activation depression (PAD) was also significantly increased with contralateral stimulation in Biceps Brachii ( p = 0.001, F = 9.3, η2 = 0.44), Triceps Brachii ( p < 0.05, F = 5.4, η2 = 0.31) and Flexor Carpi Radialis ( p < 0.001, F = 17.4, η2 = 0.59)., Conclusions: A level of unilateral motor pool selectivity may be attained by altering stimulus intensity and location during cervical tSCS. Optimising these parameters may improve the efficacy of this neuromodulation method in clinical cohorts.

Caenorhabditis elegans larvae display developmental plasticity in response to environmental conditions: in adverse conditions, second-stage larvae enter a reversible, long-lived dauer stage instead of proceeding to reproductive adulthood. Dauer entry interrupts vulval induction and is associated with a reprogramming-like event that preserves the multipotency of vulval precursor cells (VPCs), allowing vulval development to reinitiate if conditions improve. Vulval induction requires the LIN-3/EGF-like signal from the gonad, which activates EGFR-Ras-ERK signal transduction in the nearest VPC, P6.p. Here, using a biosensor and live imaging we show that EGFR-Ras-ERK activity is downregulated in P6.p in dauers. We investigated this process using gene mutations or transgenes to manipulate different steps of the pathway, and by analyzing LET-23/EGFR subcellular localization during dauer life history. We found that the response to EGF is attenuated at or upstream of Ras activation, and discuss potential membrane-associated mechanisms that could achieve this. We also describe other findings pertaining to the maintenance of VPC competence and quiescence in dauer larvae. Our analysis indicates that VPCs have L2-like and unique dauer stage features rather than features of L3 VPCs in continuous development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background: Timely lab results are important to clinical decision-making and hospital flow. However, at our institution, unreliable blood sample collection for patients with central venous access jeopardised this outcome and created staff dissatisfaction., Methods: A multidisciplinary team of nurses including a specialist clinical nurse leader (CNL), the hospital intravenous team and quality improvement (QI) consultants aimed to achieve >80% blood sample collection reliability among patients with central venous access by employing a simple signature/countersignature form coupled with audit-feedback and behavioural economics strategies. The form was piloted on one 25-bed unit. Data were collected for 60 weeks and interpreted per standard run chart rules., Results: Blood sample collection reliability exceeded the 80% goal by week 22. The practice was sustained on the pilot unit and spread successfully to other wards despite significant operational threats including the COVID-19 pandemic., Conclusions: At our institution, a simple signature/countersignature form supplemented by audit-feedback and behavioural economics strategies led to sustained practice change among staff. The pairing of CNL to QI consultant enhanced change potency and durability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cognitive impairments are well-documented in multiple sclerosis (MS), while speech impairments are often overlooked despite their significant effect on quality of life. For effective clinical management of multisystem conditions such as MS, consideration should be given to the interaction between deficits in multiple domains, such as speech and cognition. To evaluate speech rate measures of spontaneous and read speech, in people with MS and to examine the link between speech and cognition., Methods: Forty-five people with MS and 25 controls underwent an extensive cognitive battery, including executive functioning, information processing and memory tasks, and completed two speech tasks: a reading task and a picture description task, from which speech rate measures were derived., Results: The progressive MS cohort had reduced articulation ( p  < 0.04) and speech rate ( p  < 0.02) compared to controls and those with relapsing MS. Regression models also revealed information processing speed accounted for 18% to 30% of the variance of spontaneous speech rate measures, and 27% of read speech. Executive functioning accounted for a further 10% of the variance of speech rate in those with MS., Conclusions: The present study suggests that speech production is contingent on cognitive ability, with information processing speed and executive functioning linked with speech timing patterns., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Recent studies have reported that transcutaneous spinal stimulation (tSCS) may facilitate improved upper limb motor function in those with incomplete tetraplesia. However, little is known about how tSCS engages upper limb motor pools. This study aimed to explore the extent to which discrete upper limb motor pools can be selectively engaged via altering stimulus location and intensity. 14 participants with intact nervous systems completed two test visits, during which posterior root-muscle reflexes (PRMR) were evoked via a 3x3 cathode matrix applied over the cervicothoracic spine. An incremental recruitment curve at C7 vertebral level was initially performed to attain minimal threshold intensity (MTI) in each muscle. Paired pulses (1ms square monophasic with inter-pulse interval of 50ms) were subsequently delivered at a frequency of 0.25Hz at two intensities (MTI and [Formula: see text]) across all nine locations. in a random order. Evoked response to the 1 st (PRMR 1 ) and 2 nd (PRMR2) stimuli were recorded from four upper limb muscles. A significant effect of spinal level was observed in all muscles for PRMR 1 with greater responses recorded more caudally. Unexpectedly, contralateral cathode placement significantly increased PRMR 1 in Biceps Brachii (P=0.012), Flexor Carpi Radialis (P=0.035) and Abductor Pollicis Brevis (P=0.001). Post-activation depression (PAD) was also significantly increased with contralateral cathode placement in Biceps Brachii (P=0.001), Triceps Brachii (P=0.012) and Flexor Carpi Radialis (P=0.001). These results suggest that some level of unilateral motor pool selectivity may be attained via altering stimulus intensity and location during cervicothoracic tSCS.

Spinal cord injuries cause loss of muscle function and subsequently reduce independence. Therapeutic interventions such as transcutaneous spinal cord stimulation are increasingly being used to help improve motor functioning however, a comprehensive understanding of the biomechanical elements of movement may help optimize stimulation protocols. Twenty healthy participants completed five sit-to-stand (STS) transitions while initial knee angle and arm facilitation were altered. Electromyography (EMG) activation of four lower limb muscles and centre of pressure dynamics were recorded. Acute initial knee angles resulted in a change in duration of phases within the STS, and restrictive arm positioning caused the time to completion to increase (p=0.04). Muscle activation patterns across phases were compared and showed significant differences between phases in both the Tibialis Anterior and Rectus Femoris (p<0.006). Acute initial knee angles were also found to significantly increase Biceps Femoris activation across multiple phases (p=0.034). Altering the starting position and limb movement result in vastly different temporal and muscular strategies to complete the STS. Thus, joint angle and upper limb facilitation should be considered when designing rehabilitative interventions for clinical cohorts.

Background: A large academic medical center in the Pacific Northwest successfully introduced continuous video monitoring (CVM) as an adjunct measure to replace sitter use when appropriate. Adoption of the technology was influenced by nurse enculturation, standard work, data tracking management, and patient/family engagement. The purpose of this article is to identify critical data metrics to inform expansion of CVM programs when determining readiness for growth., Problem: There is a lack of literature to advise organizations on needed data and metrics to inform growth readiness of CVM programs. Specific indicators can support initiatives to achieve financial support for program expansion., Approach: CVM readiness for expansion is evident when metrics such as utilization rates, wait-list expansion, frontline staff perception, and sitter patient population outgrow current camera capacity., Conclusion: Successful metric analysis can inform initiatives to grow CVM programs, which, in turn, support a culture of safety at large academic medical centers for at-risk populations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Edwards, Rueckert, Smith, Abo Seada, Alansary, Almalbis, Allsop, Andersson, Arichi, Arulkumaran, Bastiani, Batalle, Baxter, Bozek, Braithwaite, Brandon, Carney, Chew, Christiaens, Chung, Colford, Cordero-Grande, Counsell, Cullen, Cupitt, Curtis, Davidson, Deprez, Dillon, Dimitrakopoulou, Dimitrova, Duff, Falconer, Farahibozorg, Fitzgibbon, Gao, Gaspar, Harper, Harrison, Hughes, Hutter, Jenkinson, Jbabdi, Jones, Karolis, Kyriakopoulou, Lenz, Makropoulos, Malik, Mason, Mortari, Nosarti, Nunes, O’Keeffe, O’Muircheartaigh, Patel, Passerat-Palmbach, Pietsch, Price, Robinson, Rutherford, Schuh, Sotiropoulos, Steinweg, Teixeira, Tenev, Tournier, Tusor, Uus, Vecchiato, Williams, Wright, Wurie and Hajnal.)

Successful cartilage engineering requires the generation of biological grafts mimicking the structure, composition and mechanical behaviour of the native tissue. Here melt electrowriting (MEW) was used to produce arrays of polymeric structures whose function was to orient the growth of cellular aggregates spontaneously generated within these structures, and to provide tensile reinforcement to the resulting tissues. Inkjet printing was used to deposit defined numbers of cells into MEW structures, which self-assembled into an organized array of spheroids within hours, ultimately generating a hybrid tissue that was hyaline-like in composition. Structurally, the engineered cartilage mimicked the histotypical organization observed in skeletally immature synovial joints. This biofabrication framework was then used to generate scaled-up (50 mm × 50 mm) cartilage implants containing over 3,500 cellular aggregates in under 15 min. After 8 weeks in culture, a 50-fold increase in the compressive stiffness of these MEW reinforced tissues were observed, while the tensile properties were still dominated by the polymer network, resulting in a composite construct demonstrating tension-compression nonlinearity mimetic of the native tissue. Helium ion microscopy further demonstrated the development of an arcading collagen network within the engineered tissue. This hybrid bioprinting strategy provides a versatile and scalable approach to engineer cartilage biomimetic grafts for biological joint resurfacing., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Developmental delays in infanthood often persist, turning into life-long difficulties, and coming at great cost for the individual and community. By examining the developing brain and its relation to developmental outcomes we can start to elucidate how the emergence of brain circuits is manifested in variability of infant motor, cognitive and behavioural capacities. In this study, we examined if cortical structural covariance at birth, indexing coordinated development, is related to later infant behaviour. We included 193 healthy term-born infants from the Developing Human Connectome Project (dHCP). An individual cortical connectivity matrix derived from morphological and microstructural features was computed for each subject (morphometric similarity networks, MSNs) and was used as input for the prediction of behavioural scores at 18 months using Connectome-Based Predictive Modeling (CPM). Neonatal MSNs successfully predicted social-emotional performance. Predictive edges were distributed between and within known functional cortical divisions with a specific important role for primary and posterior cortical regions. These results reveal that multi-modal neonatal cortical profiles showing coordinated maturation are related to developmental outcomes and that network organization at birth provides an early infrastructure for future functional skills., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 has placed unprecedented demands on hospitals. A clinical service, COVID-19 Oximetry @home (CO@h) was launched in November 2020 to support remote monitoring of COVID-19 patients in the community. Remote monitoring through CO@h aims to identify early patient deterioration and provide timely escalation for cases of silent hypoxia, while reducing the burden on secondary care., Methods: We conducted a retrospective service evaluation of COVID-19 patients onboarded to CO@h from November 2020 to March 2021 in the North Hampshire (UK) community led service (a collaboration of 15 General Practitioner (GP) practices covering 230 000 people). We have compared outcomes for patients admitted to Basingstoke and North Hampshire Hospital who were CO@h patients (COVID-19 patients with home monitoring of oxygen saturation (SpO 2 ; n=115), with non-CO@h patients (those directly admitted without being monitored by CO@h (n=633)). Crude and adjusted OR analysis was performed to evaluate the effects of CO@h on patient outcomes of 30-day mortality, Intensive care unit (ICU) admission and hospital length of stay greater than 3, 7, 14 and 28 days., Results: Adjusted ORs for CO@h show an association with a reduction for several adverse patient outcome: 30-day hospital mortality (p<0.001, OR 0.21, 95% CI 0.08 to 0.47), hospital length of stay larger than 3 days (p<0.05, OR 0.62, 95% CI 0.39 to 1.00), 7 days (p<0.001, OR 0.35, 95% CI 0.22 to 0.54), 14 days (p<0.001, OR 0.22 95% CI, 0.11 to 0.41), and 28 days (p<0.05, OR 0.21, 95% CI 0.05 to 0.59). No significant reduction ICU admission was observed (p>0.05, OR 0.43, 95% CI 0.15 to 1.04). Within 30 days of hospital admission, there were no hospital readmissions for those on the CO@h service as opposed to 8.7% readmissions for those not on the service., Conclusions: We have demonstrated a significant association between CO@h and better patient outcomes; most notably a reduction in the odds of hospital lengths of stays longer than 7, 14 and 28 days and 30-day hospital mortality., Competing Interests: Competing interests: MI-K is National Clinical Lead Deterioration & National Specialist Advisor Sepsis, NHS England and NHS Improvement., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: EDs globally are under increasing pressure through rising demand. Frequent attenders are known to have complex health needs and use a disproportionate amount of resources. We hypothesised that heterogeneity of patients' reason for attendance would be associated with multimorbidity and increasing age, and predict future attendance., Method: We analysed an anonymised dataset of all ED visits over the course of 2014 in Yorkshire, UK. We identified 15 986 patients who had five or more ED encounters at any ED in the calendar year. Presenting complaint was categorised into one of 14 categories based on the Emergency Care Data Set (ECDS). We calculated measures of heterogeneity (count of ECDs categories and entropy of categories) and examined their relationship to total number of ED visits and to patient characteristics. We examined the predictive value of these and other features on future attendance., Results: Most frequent attenders had more than one presenting complaint type. Heterogeneity increased with number of attendances, but heterogeneity adjusted for number of attendances did not vary substantially with age or sex. Heterogeneity was associated with the presence of one or more contacts for a mental health problem. For a given number of attendances, prior mental health contact but not heterogeneity was associated with further attendance., Conclusions: Heterogeneity of presenting complaint can be quantified and analysed for ED use: it is increased where there is a history of mental disorder but not with age. This suggests it reflects more than the number of medical conditions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A significant proportion of ED attendances in children may be non-urgent attendances (NUAs), which could be better managed elsewhere. This study aimed to quantify NUAs and urgent attendances (UAs) in children to ED and determine which children present in this way and when., Methods: Dataset extracted from the CUREd research database containing linked data on the provision of care in Yorkshire and Humber. Analysis focused on children's ED attendances (April 2014-March 2017). Summary statistics and odds ratios (OR) comparing NUAs and UAs were examined by: age, mode and time of arrival and deprivation alongside comparing summary statistics for waiting, treatment and total department times., Results: NUAs were more likely in younger children: OR for NUA in children aged 1-4 years, 0.82 (95% CI: 0.80 to 0.83), age 15 years, 0.39 (95% CI: 0.38 to 0.40), when compared with those under 1 year. NUAs were more likely to arrive out of hours (OOHs) compared with in hours: OR 1.19 (95% CI 1.18 to 1.20), and OOHs arrivals were less common in older children compared with those under 1 year: age 1-4 years, 0.87 (95% CI: 0.84 to 0.89) age 15 years, 0.66 (95% CI: 0.63 to 0.69). NUAs also spent less total time in the ED, with a median (IQR) of 98 min (60-147) compared with 127 min (80-185) for UAs., Conclusion: A substantial proportion of ED attendances in children are NUAs. Our data suggest there are particular groups of children for whom targeted interventions would be most beneficial. Children under 5 years would be such a group, particularly in providing accessible, timely care outside of usual community care opening hours., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors have no conflicts of interest to declare.

The Developing Human Connectome Project is an Open Science project that provides the first large sample of neonatal functional MRI data with high temporal and spatial resolution. These data enable mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organization in humans. Here, we characterize in unprecedented detail the maturation and integrity of resting state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder, which occur frequently in preterm children. Overall, we found a robust, modular, symmetrical functional brain organization at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Balance impairment is observed in up to 70% of people with MS (pwMS) and worsens with disease progression. Posturography using a force platform is the current gold standard in the measurement of balance. However, posturography has not been adequately studied or widely accepted for use as a disability outcome measure for pwMS. Importantly, the recent emergence of both successful and failed neuroprotective therapy trials in progressive MS has emphasised the need for new disability outcome measures for people with progressive MS. The main objectives of this study were to evaluate the clinical validity, reliability and feasibility of posturography as a disability metric in progressive MS., Methods: This was a prospective cross-sectional study. We recruited 73 people with progressive MS (age 18-65 years, EDSS 3.5-6.0). Participants stood in the centre of a force platform, feet comfortably apart, under various conditions: (i) eyes open (EO), (ii) eyes closed (EC) - a single task, each lasting ninety seconds; and simultaneous EO with a cognitive test: (iii) N-Back, a three-minute test whereby participants were instructed to click the mouse when two identical letters were displayed consecutively on a screen, (iv) Sustained Attention Response Task, a five-minute test whereby participants were instructed to click the mouse for every number "1″ to "9″ except "3″ - i.e., dual-tasks. Additionally, we performed a battery of validated physical and cognitive outcome measures. Posturographic data was processed using Matlab. Statistical analysis was performed using SPSS version 26. We used multiple linear regression modelling to determine whether significant univariate correlations between posturography and clinical metrics were independent of covariates that may influence the associations seen. A two-tailed significance level of 0.05 was used., Results: Of 73 participants, mean age 52.4 (8.5) years, mean MS disease duration 13.8 (10.3) years, median EDSS 5.0 (IQR 4.0-6.0), 44 (60.4%) were female. EO-Path-Length independently predicted upper extremity function (9-Hole-Peg-Test) with a larger effect size (adjusted R 2 =20.0%, p = 0.001) than that for walking measures (Timed 25-Foot Walk, adjusted R 2 =1.6%, p = 0.01; Two-Minute Walk Test, adjusted R 2 =7.2%, p = 0.002), while controlling for age, disease duration, height, weight, and sex. The addition of EO-Mediolateral-Displacement to the MS Functional Composite (MSFC) created a four-component z-score that increased the variance explained for quality of life (QOL) by 62.1%. Postural stability was significantly lower with mediolateral vs anteroposterior direction of sway, removal of vision, increased body weight, male sex, and fampridine use. Postural stability improved during dual-tasks compared to EO single task. Posturography detected significant worsening of balance over a single prolonged stance., Conclusion: Postural stability independently predicted a wide range of clinical metrics including upper extremity function, walking ability, cognition and QOL, therefore establishing construct and concurrent validity as a disability outcome measure for people with progressive MS. Additionally, posturography is a quantitative, non-invasive, quick-and-easy-to-administer, and highly sensitive device, demonstrating its high feasibility for use as a time- and resource-efficient disability metric in neuroprotective therapy trials for progressive MS., (Copyright © 2021. Published by Elsevier B.V.)

The NHS 111 telephone advice and triage service is a vital part of the management of urgent and emergency care (UEC) services in England. Demand for NHS 111 advice has increased since its introduction in 2013, and the service is of particular importance in light of the current pandemic and resulting increased demand for emergency care. Currently, little is known about the effectiveness of NHS 111 in terms of the appropriateness of the advice given, or about the compliance of patients with that advice. We aimed to address this issue by analysing a large linked routine dataset of all NHS 111 calls (n = 3,631,069) and subsequent emergency department (ED) attendances made in the Yorkshire & Humber region from March 2013-March 2017. We found that many patients do not comply with advice, with 11% (n = 289,748) of patients attending ED when they are advised to self-care or seek primary care. We also found that a considerable number of these patients are further classed as urgent (88%, n = 255,931) and a substantial minority (37%, 106,207) are subsequently admitted to hospital. Further, many patients who are sent an ambulance or told to attend ED are classed as non-urgent upon attending ED (9%, n = 42,372). This research suggests that the level at which NHS 111 is currently triaging results in many hundreds of thousands of mis-triaged cases annually. Additionally, patients frequently do not comply with the advice they receive. This has implications for understanding the accuracy and efficiency of triaging systems., Competing Interests: The authors have declared that no competing interests exist.

Background: Sitters are often used in the inpatient setting as a measure to ensure safety of patients with cognitive and behavioral concerns., Problem: Sitters are costly, and evidence is lacking that their presence produces safer outcomes. Continuous video monitoring is a safe alternative; yet, there is a lack of best practices and implementation strategies., Approach: A large academic medical center in the Pacific Northwest introduced continuous video monitoring as an adjunct measure to replace sitter use when appropriate. Adoption of the technology was influenced by nurse enculturation, leader standard work (standard parameters used by nurse leaders for process improvement), data tracking management, and patient/family feedback., Outcomes: Continuous video monitoring is a bridge for the nursing staff to enhance safety for patients and an additional safety intervention when sitter use is not reasonable., Conclusion: Utilizing technology such as continuous video monitoring can relieve sitters to allow for optimal productivity, increased safety, cost reduction, and nurse/family satisfaction., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc.)

The developing Human Connectome Project (dHCP) aims to create a detailed 4-dimensional connectome of early life spanning 20-45 weeks post-menstrual age. This is being achieved through the acquisition of multi-modal MRI data from over 1000 in- and ex-utero subjects combined with the development of optimised pre-processing pipelines. In this paper we present an automated and robust pipeline to minimally pre-process highly confounded neonatal resting-state fMRI data, robustly, with low failure rates and high quality-assurance. The pipeline has been designed to specifically address the challenges that neonatal data presents including low and variable contrast and high levels of head motion. We provide a detailed description and evaluation of the pipeline which includes integrated slice-to-volume motion correction and dynamic susceptibility distortion correction, a robust multimodal registration approach, bespoke ICA-based denoising, and an automated QC framework. We assess these components on a large cohort of dHCP subjects and demonstrate that processing refinements integrated into the pipeline provide substantial reduction in movement related distortions, resulting in significant improvements in SNR, and detection of high quality RSNs from neonates., Competing Interests: Declaration of Competing Interest MJ, SS, and JA receive royalties from the commercial licensing of FSL (it is free for non-commercial use). The authors report no other conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Interruptions to neurodevelopment during the perinatal period may have long-lasting consequences. However, to be able to investigate deviations in the foundation of proper connectivity and functional circuits, we need a measure of how this architecture evolves in the typically developing brain. To this end, in a cohort of 241 term-born infants, we used magnetic resonance imaging to estimate cortical profiles based on morphometry and microstructure over the perinatal period (37-44 weeks postmenstrual age, PMA). Using the covariance of these profiles as a measure of inter-areal network similarity (morphometric similarity networks; MSN), we clustered these networks into distinct modules. The resulting modules were consistent and symmetric, and corresponded to known functional distinctions, including sensory-motor, limbic, and association regions, and were spatially mapped onto known cytoarchitectonic tissue classes. Posterior regions became more morphometrically similar with increasing age, while peri-cingulate and medial temporal regions became more dissimilar. Network strength was associated with age: Within-network similarity increased over age suggesting emerging network distinction. These changes in cortical network architecture over an 8-week period are consistent with, and likely underpin, the highly dynamic processes occurring during this critical period. The resulting cortical profiles might provide normative reference to investigate atypical early brain development., (© The Author(s) 2020. Published by Oxford University Press.)

Introduction: The urgent and emergency care (UEC) system is struggling with increased demand, some of which is clinically unnecessary. Patients suffering suspected seizures commonly present to EDs, but most seizures are self-limiting and have low risk of short-term adverse outcomes. We aimed to investigate the flow of suspected seizure patients through the UEC system using data linkage to facilitate the development of new models of care., Methods: We used a two-stage process of deterministic linking to perform a cross-sectional analysis of data from adults in a large region in England (population 5.4 million) during 2014. The core dataset comprised a total of 739 436 ambulance emergency incidents, 1 033 778 ED attendances and 362 358 admissions., Results: A high proportion of cases were successfully linked (86.9% ED-inpatient, 77.7% ED-ambulance). Suspected seizures represented 2.8% of all ambulance service incidents. 61.7% of these incidents led to dispatch of a rapid-response ambulance (8 min) and 72.1% were conveyed to hospital. 37 patients died before being conveyed to hospital and 24 died in the ED (total 61; 0.3%). The inpatient death rate was 0.4%. Suspected seizures represented 0.71% of ED attendances, 89.8% of these arrived by emergency ambulance, 45.4% were admitted and 44.5% of these admissions lasted under 48 hours., Conclusions: This study confirms previously published data from smaller unlinked datasets, validating the linkage method, and provides new data for suspected seizures. There are significant barriers to realising the full potential of data linkage. Collaborative action is needed to create facilitative governance frameworks and improve data quality and analytical capacity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fragile X-associated Tremor/Ataxia Syndrome is a genetic neurodegenerative disorder affecting carriers of the FMR1 premutation. Not all carriers develop the condition and the age of onset is somewhat variable. A greater understanding of disease progression would be beneficial. Eight carriers and five controls matched by age, sex, and dominant hand volunteered to perform a sway task on a force platform while EEG was simultaneously recorded. Sway parameters were extracted from the movement data at important timepoints throughout their sway cycles and matched to their EEG activity. Distributed source analysis was applied. While there initially appeared to be differences in neural activity between the two groups in the anterior lobe, the right posterior lobe, the right superior parietal lobule and the right parietal lobe, these differences did not survive correction for multiple comparisons.

Clinical assessment of Multiple Sclerosis relies heavily on the Expanded Disability Status Scale, a non-linear rating system based on physician assessment of disease progression and walking ability. This inherently makes this method both subjective and limited in repeatability. This study developed a technically derived outcome measure of posture to compare a cohort of Multiple Sclerosis and Control subjects during an Eyes-Open and Eyes-closed task. Analysing traditional sway parameters and a multiscale entropy derived complexity index of posturography showed a significant difference in medio-lateral sway between groups during the Eyes-Open condition. This technically derived outcome measure may be of clinical benefit in the longitudinal assessment of the functional impact of balance in MS cohorts and assist in the evaluation of pharmaceutical and rehabilitation interventions.

FRM1 premutation carriers exhibit various subtle deficits in balance and stability, prior to the development of the movement disorder Fragile X Associated Tremor/Ataxia Syndrome (FXTAS). Force plate posturography has increasingly been combined with the temporal sensitive imaging methods such as EEG to offer insight into the neural mechanisms which govern postural control. This study investigated cortical theta power during continuous balance and its relationship to balance performance in Fragile X premutation carriers. Eight premutation carriers and 6 controls stood on a force platform under altered sensory and cognitive conditions while postural sway and high-density EEG data were simultaneously recorded. Carriers exhibited greater sway area when sensory input was reduced (p=0.01) and cognitive load was increased (p=0.01), as well as significantly reduced frontal theta power compared to the Control Group. The relationship between theta power and postural control seen in the control group may indicate an increase in error detection caused by reduced visual input and greater discrepancies between expected and actual balance state. While the lower theta power in frontal regions of carriers may indicate a disruption in neural networks underpinning postural control. Such results provide new insight into the neural correlates of balance control in Fragile X premutation carriers.