Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (β = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.

Abstract Background Autism spectrum disorder (ASD) is a neurobehavioural disorder, characterized by abnormal affiliative and socio-emotional responses which are generally regulated by certain neuropeptides in the hypothalamus (an anatomic component of the ventral diencephalon (VD)). The use of volumetric MRI for studying VD volume change could provide a novel approach for identification of structural brain changes in ASD; this could assist in understanding the pathophysiology of ASD and would reflect on treatment strategies. The aim of the current work was to investigate the role of MRI volumetric analysis of the ventral diencephalon in young children diagnosed with autism spectrum disorder. Methods Fifty children diagnosed with ASD underwent volumetric brain analysis, on a fully automated MRI brain volumetry system (volBrain), with voxel-based morphometry of various segmental structures of the brain including the VD, using vol2Brain 1.0 pipeline software analysis suite. Results There were 48 out of 50 children who demonstrated abnormal VD volume which was found below the normal limits compared with reference standard normalized volume. All cases were normocephalic demonstrating normal intra-cranial cavity volumes. Forty out of fifty cases showed increased total volume of grey matter, and eighteen out of fifty cases showed increased total volume of white matter. Regarding the amygdala and hippocampus, there were only two cases (4.0%) which showed slightly increased relative volume of the total amygdala, and two other cases (4.0%) demonstrated increased relative volume of the total hippocampus. Comparison between the autistic patients and normal references revealed a significant difference regarding the VD volume and total volume of grey matter, whereas no significant differences were found regarding the white matter amygdala and hippocampus. Conclusions Based on the consistent significant volume decrease in the ventral diencephalon in patients with childhood autism, this study concluded that volumetric MRI analysis could be useful for diagnosis of childhood spectrum disorder and could be utilized as a reliable screening method in the clinically vague cases. Further study with a larger sample size including more age groups is recommended for more validation of the results.

Background: Evidence suggests that certain groups of orthopaedic patients have an increased prevalence of mental health disorders than the general population. This scoping review aims to evaluate the effect of pre-operative mental health on outcomes of foot and ankle surgery. Methods: A literature search was performed in four databases. Studies investigating a relationship between preoperative mental health and postoperative patient reported outcome measures (PROMs), complications, readmissions or reoperations were included. Results: Of the 19 studies investigating the effect of preoperative mental health on PROMs, 16 (84.2%) reported a significant relationship between poorer preoperative mental health and inferior postoperative PROMs. Poorer mental health was associated with an increased rate of complications, readmissions and/or reoperations in four studies. Conclusions: Poorer preoperative mental health is associated with significantly inferior outcomes following foot and ankle surgery. Clinicians should evaluate mental health to stratify likely outcomes and aid in the management of patient expectations. Level of evidence: Level IV: Scoping review of Level II-IV studies.

Point-of-care haemoglobin measurement devices may play an important role in the antenatal detection of anaemia in pregnant people and may be useful in guiding blood transfusion during resuscitation in obstetric haemorrhage. We compared baseline haemoglobin variability of venous and capillary HemoCue® haemoglobin, and Masimo® Rad-67 Pulse CO-Oximeter haemoglobin with laboratory haemoglobin in people on the day of their planned vaginal birth. A total of 180 people undergoing planned vaginal birth were enrolled in this prospective observational study. Laboratory haemoglobin was compared with HemoCue and Masimo Rad-67 Pulse CO-Oximeter measurements using Bland-Altman analysis, calculating mean difference (bias) and limits of agreement. Five (2.8%) people had anaemia (haemoglobin < 110 g.l-1 ). Laboratory haemoglobin and HemoCue venous haemoglobin comparison showed an acceptable bias (SD) 0.7 (7.54) g.l-1 (95%CI -0.43-1.79), with limits of agreement -14.10-15.46 g.l-1 and acceptable agreement range of 29.6 g.l-1 . Laboratory and HemoCue capillary haemoglobin comparison showed an unacceptable bias (SD) 13.3 (14.12) g.l-1 (95%CI 11.17-15.34), with limits of agreement - 14.42-40.93 g.l-1 and unacceptable agreement range of 55.3 g.l-1 . Laboratory and Masimo haemoglobin comparison showed an unacceptable bias (SD) -14.0 (11.15) g.l-1 (95%CI -15.63 to -12.34), with limits of agreement to -35.85 to 7.87 g.l-1 and acceptable agreement range of 43.7 g.l-1 . Venous HemoCue, with its acceptable bias and limits of agreement, should be applied more widely in the antenatal setting to detect, manage and risk stratify pregnant people with anaemia. HemoCue capillary measurement under-estimated haemoglobin and Masimo haemoglobin measurement over-estimated, limiting their clinical use. Serial studies are needed to determine if the accuracy of venous HemoCue haemoglobin measurement is sustained in other obstetric settings.

Aim: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. Design: Parallel two-arm, cluster-level randomized controlled trial. Methods: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. Results: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. Conclusion: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. Implications for the profession and/or patient care: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. Impact: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. Reporting method: CONSORT and CONSERVE. Patient or public contribution: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Introduction: Total knee arthroplasty (TKA) can be performed with either conventional off-the-shelf (OTS) or customized individually-made (CIM) implants. The evidence for CIM implants is limited and variable, and the aim of this review was to compare clinical and radiological outcomes between CIM and OTS implants. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Studies reporting on clinical, radiological, or alignment outcomes for CIM and OTS implants were selected. The studies were appraised using the Methodical index for non-randomized studies tool. Results: Twenty-three studies fulfilled the inclusion criteria. The studies comprised 2856 CIM and 1877 OTS TKAs. Revision rate was higher with CIM (5.9%) compared to OTS (3.7%) implants [OR 1.23(95% CI 0.69-2.18)]. Manipulation under anesthesia (MUA) was higher in CIM (2.2%) compared to OTS (1.1%) group [OR 2.95(95% CI 0.95-9.13)] and complications rate was higher in CIM (5%) vs. OTS (4.5%) [OR 1.45(95% CI 0.53-3.96)] but neither reached statistical significance. Length of stay was significantly shorter in CIM group 2.9 days vs. 3.5 days [MD - 0.51(95% CI - 0.82 to - 0.20)]. Knee Society Score showed no difference between CIM and OTS groups for Knee 90.5 vs. 90.6 [MD - 0.27(95% CI - 4.27 to 3.73)] and Function 86.1 vs. 83.1 [MD 1.51(95% CI - 3.69 to 6.70)]. Conclusion: CIM implants in TKA have theoretical benefits over OTS prostheses. However, in this present review, CIM implants were associated with higher revisions, MUA, and overall complication rates. There was no difference in outcome score and CIM implants did not improve overall target alignment; however, more CIM TKAs were found to be in the HKA target zone compared to OTS TKAs. The findings of this review do not support the general utilization of CIM over OTS implants in TKA.

AIMS: Long-term follow-up and monitoring of asymptomatic shoulder and elbow arthroplasty remains contentious, with a wide spectrum of non-evidence-based mechanisms used. This scoping review aims to outline related evidence, thereby informing research requirements. METHODS: Studies relevant to shoulder and elbow arthroplasty follow-up, surveillance and time-related failure were included. The review included randomised controlled trials, systematic reviews and economic studies indexed in MEDLINE, Embase, Cochrane CDSR and Cochrane CENTRAL since 1 January 2012. In addition, all registry studies, follow-up studies, cohort studies and case reports indexed in MEDLINE since 1 January 2020 were included. The screening was undertaken by two reviewers. Key characteristics of each study were described, alongside a narrative review. RESULTS: Twenty-one articles were included. We were unable to identify evidence that long-term follow-up and monitoring of asymptomatic shoulder and elbow arthroplasty identifies failure or leads to a revision that is of reduced patient morbidity and cost. In addition, no evidence was apparent to inform whether patients will self-present with a failing implant. Several surveillance mechanisms were identified. CONCLUSION: This scoping review highlights the paucity of evidence related to long-term follow-up and monitoring of shoulder and elbow arthroplasty, and the need for high-quality data to inform the development of evidence-based care pathways.

Introduction: Current practice following injury within the United Kingdom is to receive surgery, at the institution of first contact regardless of ability to provide timely intervention and inconsiderate of neighbouring hospital resource and capacity. This can lead to a mismatch of demand and capacity, delayed surgery and stress within hospital systems, particularly with regards to elective services. We demonstrate through a multicentre, multinational study, the impact of this at scale. Methodology: ORTHOPOD data collection period was between 22/08/2022 and 16/10/2022 and consisted of two arms. Arm 1 captured orthopaedic trauma caseload and capacity in terms of sessions available per centre and patients awaiting surgery per centre per given week. Arm 2 recorded patient and injury demographics, time of decision making, outpatient and inpatient timeframes as well as time to surgery. Hand and spine cases were excluded. For this regional comparison, regional trauma networks with a minimum of four centres enroled onto the ORTHOPOD study were exclusively analysed. Results: Following analysis of 11,202 patient episodes across 30 hospitals we found no movement of any patient between hospitals to enable prompt surgery. There is no current system to move patients, between regional centres despite clear discrepancies in workload per capacity across the United Kingdom. Many patients wait for days for surgery when simple transfer to a neighbouring hospital (within 10 miles in many instances) would result in prompt care within national guidelines. Conclusion: Most trauma patients in the United Kingdom are managed exclusively at the place of first presentation, with no consideration of alternative pathways to local hospitals that may, at that time, offer increased operative capacity and a shorter waiting time. There is no oversight of trauma workload per capacity at neighbouring hospitals within a regional trauma network. This leads to a marked disparity in waiting time to surgery, and subsequently it can be inferred but not proven, poorer patient experience and outcomes. This inevitably leads to a strain on the overall trauma system and across several centres can impact on elective surgery recovery. We propose the consideration of inter-regional network collaboration, aligned with the Major Trauma System.

Aims: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. Materials and methods: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. Results: to date: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. Future: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

As digital pathology replaces conventional glass slide microscopy as a means of reporting cellular pathology samples, the annotation of digital pathology whole slide images is rapidly becoming part of a pathologist's regular practice. Currently, there is no recognizable organization of these annotations, and as a result, pathologists adopt an arbitrary approach to defining regions of interest, leading to irregularity and inconsistency and limiting the downstream efficient use of this valuable effort. In this study, we propose a Standardized Annotation Reporting Style for digital whole slide images. We formed a list of 167 commonly annotated entities (under 12 specialty subcategories) based on review of Royal College of Pathologists and College of American Pathologists documents, feedback from reporting pathologists in our NHS department, and experience in developing annotation dictionaries for PathLAKE research projects. Each entity was assigned a suitable annotation shape, SNOMED CT (SNOMED International) code, and unique color. Additionally, as an example of how the approach could be expanded to specific tumor types, all lung tumors in the fifth World Health Organization of thoracic tumors 2021 were included. The proposed standardization of annotations increases their utility, making them identifiable at low power and searchable across and between cases. This would aid pathologists reporting and reviewing cases and enable annotations to be used for research. This structured approach could serve as the basis for an industry standard and be easily adopted to ensure maximum functionality and efficiency in the use of annotations made during routine clinical examination of digital slides.