Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors.

Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically up-regulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally acting chromatin remodeller. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.

Myosin II tension sensors visualize force generation within the actin cytoskeleton in living cells.

Nonmuscle myosin II (NMII) generates cytoskeletal forces that drive cell division, embryogenesis, muscle contraction and many other cellular functions. However, at present there is no method that can directly measure the forces generated by myosins in living cells. Here, we describe a Förster resonance energy transfer (FRET)-based tension sensor that can detect myosin-associated force along the filamentous actin network. Fluorescence lifetime imaging microscopy (FLIM)-FRET measurements indicate that the forces generated by NMII isoform B (NMIIB) exhibit significant spatial and temporal heterogeneity as a function of donor lifetime and fluorophore energy exchange. These measurements provide a proxy for inferred forces that vary widely along the actin cytoskeleton. This initial report highlights the potential utility of myosin-based tension sensors in elucidating the roles of cytoskeletal contractility in a wide variety of contexts.

The Swi-Snf chromatin remodeling complex mediates gene repression through metabolic control.

In eukaryotes, ATP-dependent chromatin remodelers regulate gene expression in response to nutritional and metabolic stimuli. However, altered transcription of metabolic genes may have significant indirect consequences which are currently poorly understood. In this study, we use genetic and molecular approaches to uncover a role for the remodeler Swi-Snf as a critical regulator of metabolism. We find that snfΔ mutants display a cysteine-deficient phenotype, despite growth in nutrient-rich media. This correlates with widespread perturbations in sulfur metabolic gene transcription, including global redistribution of the sulfur-sensing transcription factor Met4. Our findings show how a chromatin remodeler can have a significant impact on a whole metabolic pathway by directly regulating an important gene subset and demonstrate an emerging role for chromatin remodeling complexes as decisive factors in metabolic control.

The experience of patients undergoing aseptic, elective revision knee joint replacement surgery: a qualitative study.

BACKGROUND: Around 6,000 revision knee replacement procedures are performed in the United Kingdom each year. Three-quarters of procedures are for aseptic, elective reasons, such as progressive osteoarthritis, prosthesis loosening/wear, or instability. Our understanding of how we can best support these patients undergoing revision knee replacement procedures is limited. This study aimed to explore patients' experiences of having a problematic knee replacement and the impact of undergoing knee revision surgery for aseptic, elective reasons. METHODS: Qualitative semi structured interviews with 15 patients (8 women, 7 men; mean age 70 years: range 54-81) who had undergone revision knee surgery for a range of aseptic, elective indications in the last 12 months at an NHS Major Revision Knee Centre. Interviews were audio-recorded, transcribed, de-identified and analysed using reflexive thematic analysis. RESULTS: We developed six themes: Soldiering on; The challenge of navigating the health system; I am the expert in my own knee; Shift in what I expected from surgery; I am not the person I used to be; Lingering uncertainty. CONCLUSIONS: Living with a problematic knee replacement and undergoing knee revision surgery has significant impact on all aspects of patients' lives. Our findings highlight the need for patients with problematic knee replacements to be supported to access care and assessment, and for long-term psychological and rehabilitation support before and after revision surgery.

Anteromedial knee osteoarthritis (AMOA) evaluated with magnetic resonance imaging (MRI): a cohort study of 100 patients.

INTRODUCTION: Magnetic resonance imaging (MRI) scans are increasingly used for knee osteoarthritis evaluation and preoperative planning before unicompartmental knee arthroplasty (UKA), and often patients already have MRI scans before their initial surgeon consultation. This highlights the need for surgeons to understand anteromedial osteoarthritis (AMOA) patterns on MRI. Hence, we aim to describe MRI findings in patients with AMOA meeting current indications for medial UKA. MATERIALS AND METHODS: We analysed MRI scans from 100 knees evaluated for UKA between 2006 and 2013. Inclusion criteria comprised full-thickness medial compartment loss and intact lateral compartment joint space on preoperative radiographs. Assessment included cartilage lesions, osteophytes, meniscal damage, and anterior-cruciate ligament (ACL) status on tibial and femoral surfaces. Final decision to proceed with UKA relied on intraoperative findings, independent of MRI. RESULTS: Complete anteromedial tibial and femoral cartilage loss preserved posterior cartilage rims was evident in all cases. Cartilage thinning occurred in the lateral compartment in 34% of cases. While 62% displayed lateral osteophytes, only 6 exhibited small areas of full-thickness cartilage loss. ACL abnormalities varied: 27% normal, 3% ruptured, and 70% had intrasubstance high signal. Larger osteophytes in the medial (p = 0.012) and lateral (p = 0.002) intercondylar notch correlated significantly with ACL damage. All underwent medial UKA, with no evidence of areas with full lateral compartment cartilage loss intraoperatively. CONCLUSIONS: The MRI findings confirmed the radiographic diagnosis of bone-on-bone medial disease but highlights a range of findings in the ACL, lateral compartment, and patellofemoral joint compartment for patients who met the current x-ray and intraoperative indication for UKA. Further research is required to understand if these MRI changes will affect long-term outcomes.

Analysis of Trans-Ancestral SLE Risk Loci Identifies Unique Biologic Networks and Drug Targets in African and European Ancestries.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of African ancestry (AA) experience the disease more severely and with an increased co-morbidity burden compared to European ancestry (EA) populations. We hypothesize that the disparities in disease prevalence, activity, and response to standard medications between AA and EA populations is partially conferred by genomic influences on biological pathways. To address this, we applied a comprehensive approach to identify all genes predicted from SNP-associated risk loci detected with the Immunochip. By combining genes predicted via eQTL analysis, as well as those predicted from base-pair changes in intergenic enhancer sites, coding-region variants, and SNP-gene proximity, we were able to identify 1,731 potential ancestry-specific and trans-ancestry genetic drivers of SLE. Gene associations were linked to upstream and downstream regulators using connectivity mapping, and predicted biological pathways were mined for candidate drug targets. Examination of trans-ancestral pathways reflect the well-defined role for interferons in SLE and revealed pathways associated with tissue repair and remodeling. EA-dominant genetic drivers were more often associated with innate immune and myeloid cell function pathways, whereas AA-dominant pathways mirror clinical findings in AA subjects, suggesting disease progression is driven by aberrant B cell activity accompanied by ER stress and metabolic dysfunction. Finally, potential ancestry-specific and non-specific drug candidates were identified. The integration of all SLE SNP-predicted genes into functional pathways revealed critical molecular pathways representative of each population, underscoring the influence of ancestry on disease mechanism and also providing key insight for therapeutic selection.

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. METHODS: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score-4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. FINDINGS: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5-13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. INTERPRETATION: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. FUNDING: The UK National Institute for Health Research Health Technology Assessment Programme.

The recombinant Link module of human TSG-6 suppresses cartilage damage in models of osteoarthritis: A potential disease-modifying OA drug.

OBJECTIVE: To investigate the role of endogenous TSG-6 in human osteoarthritis (OA) and assess the disease-modifying potential of a TSG-6-based biological treatment in cell, explant and animal models of OA. DESIGN: Knee articular cartilages from OA patients were analyzed for TSG-6 protein and mRNA expression using immunohistochemistry and RNAscope, respectively. The inhibitory activities of TSG-6 and its isolated Link module (Link_TSG6) on cytokine-induced degradation of OA cartilage explants were compared. Human mesenchymal stem/stromal cell-derived chondrocyte pellet cultures were used to determine the effects of Link_TSG6 and full-length TSG-6 on IL-1α-, IL-1ß-, or TNF-stimulated ADAMTS4, ADAMTS5, and MMP13 mRNA expression. Link_TSG6 was administered i.a. to the rat ACLTpMMx model; cartilage damage and tactile allodynia were assessed. RESULTS: TSG-6 is predominantly associated with chondrocytes in regions of cartilage damage where high TSG-6 expression aligns with low MMP13, the major collagenase implicated in OA progression. Link_TSG6 is more potent than full-length TSG-6 at inhibiting cytokine-mediated matrix breakdown in human OA cartilage explants;>50% of donor cartilages, from 59 tested, were responsive to Link_TSG6 treatment. Link_TSG6 also displayed more potent effects in 3D pellet cultures, suppressing ADAMTS4, ADAMTS5, and MMP13 gene expression, which was consistent with reduced aggrecanase and collagenase activities in explant cultures. Link_TSG6 treatment reduced touch-evoked pain behavior and dose-dependently inhibited cartilage damage in a rodent model of surgically-induced OA. CONCLUSIONS: Link_TSG6 has enhanced chondroprotective activity compared to the full-length TSG-6 protein and shows potential as a disease modifying OA drug via its inhibition of aggrecanase and collagenase activity.

Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs.

5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding-defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.

Less pain reported 5 years after cementless compared to cemented unicompartmental knee replacement: an analysis of pain, neuropathy, and co-morbidity scores.

PURPOSE: To compare patient-reported pain scores and assess the influence of neuropathy and co-morbidity, on knee pain following cemented and cementless medial unicompartmental knee replacement (UKR) 5 years after surgery. METHOD: In this longitudinal study, 262 cemented and 262 cementless Oxford UKR performed for the same indications and with the same techniques were recruited. Patients were reviewed at five years, evaluating patient-reported pain and association with clinical outcomes. Intermittent and Constant Osteoarthritis Pain (ICOAP), PainDETECT (PD), Charnley score, Oxford Knee Score (OKS) and American Knee Society Score (AKSS) were compared. RESULTS: In both cohorts, intermittent pain was more common than constant pain (47% vs 21%). Cementless knees reported significantly less pain than cemented (ICOAP-Total 5/100 vs 11/100, p < 0.0001). A greater proportion of cementless knees experienced no pain at all (ICOAP = 0/100, 61% vs 43%, p < 0.0001) and 75% fewer experienced severe or extreme pain. Pain sub-scores in PD, OKS and AKSS follow this trend. Pain was unlikely to be neuropathic (PD positive: 5.26%), but patients reporting high levels of 'strongest' pain were three times more likely to be neuropathic. Patients with co-morbidities (Charnley C) experienced greater pain than those without (Charnley A+B) across all knee-specific scores, despite scores being knee specific. CONCLUSION: Both cemented and cementless UKR in this study had substantially less pain than that reported in literature following TKR. Cementless UKR had significantly less pain than cemented UKR in all scores. Two-thirds of patients with a cementless UKR had no pain at all at 5 years, and pain experienced was most likely to be mild and intermittent with no patients in severe or extreme pain. Patients with cementless UKR that had higher levels of pain were more likely to have co-morbidity or evidence or neuropathic pain. It is unclear why cementless UKR have less pain than cemented; further study is necessary.

Re-revision Knee Arthroplasty in a Tertiary Center: Infection and Multiple Previous Surgeries Were Associated With Poor Early Clinical and Functional Outcomes.

BACKGROUND: The incidence of re-revision knee arthroplasty (re-revision KA) is increasing and associated with high complication and failure rates. The aim of this study was to investigate re-revision rates, complications, and patient-reported outcomes following re-revision KA and factors associated with poor outcome. METHODS: This was a retrospective cohort study of 206 patients (250 knees) undergoing re-revision KA at a major revision center from 2015 to 2018. The mean follow-up was 26 months (range, 0 to 61) and mean age at re-revision KA was 69 years (range, 31 to 91 years). The main indications for surgery were prosthetic joint infection (PJI) (n = 171/250, 68.4%) and aseptic loosening (n = 25/250, 10.0%). We compared re-revision rates, joint function, and complications for aseptic and infective indications. Logistic regressions were performed to identify risk factors for further reoperation. RESULTS: The estimated re-revision rates at 2 years were 28.7% (95% confidence interval [CI]: 22.7-35.9) and at 4 years were 42.0% (95% CI: 32.8-52.6). Mean Oxford Knee Score was 26 points (range, 1 to 48). Mean EuroQoL-5D-5L utility was 0.539 (range, -0.511 to 1.000). Multivariable analyses demonstrated that PJI (Odds Ratio [OR] 2.39, 95% CI 1.06-5.40, P = .036), greater number of previous surgeries (OR 1.18, 95% CI 1.04-1.33, P = .008), and higher Elixhauser score (OR 1.06, 95% CI 1.01-1.13, P = .045) were independently associated to further surgery. CONCLUSION: Re-revision KA carried a high risk of early failure. Multiple revised joints and patients with more comorbidities had worse function. Patients undergoing re-revision KA for PJI should be counseled to expect higher failure rates and complications than patients who have aseptic indications.

Effect of a Protocol to Reduce Radiographic Imaging in Pediatric Patients With Suspected Fractures.

BACKGROUND: Children with suspected fractures are typically evaluated with multiple x-rays. This approach can add time, discomfort, and radiation exposure without clinical benefit. The purpose of this study was to determine whether a focused radiographic protocol could reduce the number of x-rays performed without missing any fractures. METHODS: Pediatric patients presenting at 2 sites within an academic medical center [urgent care (UC) and the emergency department(ED)] for a suspected fracture were identified. There were 495 patients (UC, 409; ED, 86) over a 3-month period. A retrospective chart review was performed to characterize the standard x-rays performed. Using this data, a simplified protocol was developed and distributed. Subsequently, 333 patients (UC, 259; ED, 74) were evaluated over the same period 1-year later. The main outcome measures included the final diagnosis, the total number of x-rays, the number of anatomic areas imaged, visit length, and the time for additional trips to radiology. Charts were reviewed to identify any missed injuries. Welch 2-sample t tests and Fisher exact tests were used for statistical analysis. RESULTS: After implementing the radiographic protocol, there was a significant reduction in the number of x-ray views, 3.4 versus 5.1 ( P <0.001). There was a decrease in imaging of multiple anatomic areas with the largest reduction occurring in patients presenting with elbow injuries (9% vs. 44%, P <0.001). No difference was found in the rate of patients sent back to radiology (6% vs. 7%, P =0.67). However, among patients presenting with outside imaging, significantly fewer were sent to radiology for additional x-rays (29% vs. 50%, P <0.01). CONCLUSION: A simple radiographic protocol for evaluating pediatric patients with suspected fractures safely led to a decrease in the overall number of x-rays without missing any injuries. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Indications and techniques for non-articulating spacers in massive bone loss following prosthetic knee joint infection: a scoping review.

INTRODUCTION: Prosthetic joint infection (PJI) is a destructive complication of knee replacement surgery (KR). In two-stage revision a spacer is required to maintain limb length and alignment and provide a stable limb on which to mobilise. Spacers may be articulating or static with the gold standard spacer yet to be defined. The aims of this scoping review were to summarise the types of static spacer used to treat PJI after KR, their indications for use and early complication rates. METHODS: We conducted a scoping review based on the Joanna Briggs Institute's "JBI Manual for Evidence Synthesis" Scoping review reported following Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. MEDLINE, EMBASE and CINAHL were searched from 2005 to 2022 for studies on the use of static spacers for PJI after KR. RESULTS: 41 studies (1230 patients/knees) were identified describing 42 static spacer constructs. Twenty-three (23/42 [54.2%]) incorporated cement augmented with metalwork, while nineteen (19/42, [45.9%]) were made of cement alone. Spacers were most frequently anchored in the diaphysis (22/42, [53.3%]), particularly in the setting of extensive bone loss (mean AORI Type = F3/T3; 11/15 studies 78.3% diaphyseal anchoring). 7.1% (79 of 1117 knees) of static spacers had a complication requiring further surgery prior to planned second stage with the most common complication being infection (86.1%). CONCLUSIONS: This study has summarised the large variety in static spacer constructs used for staged revision KR for PJI. Static spacers were associated with a high risk of complications and further work in this area is required to improve the quality of care in this vulnerable group.

Resolving the full spectrum of human genome variation using Linked-Reads.

Large-scale population analyses coupled with advances in technology have demonstrated that the human genome is more diverse than originally thought. To date, this diversity has largely been uncovered using short-read whole-genome sequencing. However, these short-read approaches fail to give a complete picture of a genome. They struggle to identify structural events, cannot access repetitive regions, and fail to resolve the human genome into haplotypes. Here, we describe an approach that retains long range information while maintaining the advantages of short reads. Starting from ∼1 ng of high molecular weight DNA, we produce barcoded short-read libraries. Novel informatic approaches allow for the barcoded short reads to be associated with their original long molecules producing a novel data type known as "Linked-Reads". This approach allows for simultaneous detection of small and large variants from a single library. In this manuscript, we show the advantages of Linked-Reads over standard short-read approaches for reference-based analysis. Linked-Reads allow mapping to 38 Mb of sequence not accessible to short reads, adding sequence in 423 difficult-to-sequence genes including disease-relevant genes STRC, SMN1, and SMN2 Both Linked-Read whole-genome and whole-exome sequencing identify complex structural variations, including balanced events and single exon deletions and duplications. Further, Linked-Reads extend the region of high-confidence calls by 68.9 Mb. The data presented here show that Linked-Reads provide a scalable approach for comprehensive genome analysis that is not possible using short reads alone.

Utility of pre-operative haemoglobin concentration to guide peri-operative blood tests for hip and knee arthroplasty: A decision curve analysis.

OBJECTIVE: Assess the prognostic value of pre-operative haemoglobin concentration (Hb) for identifying patients who develop severe post-operative anaemia or require blood transfusion following primary total hip or knee, or unicompartmental knee arthroplasty (THA, TKA, UKA). BACKGROUND: Pre-operative group and save (G&S), and post-operative Hb measurement may be unnecessary for many patients undergoing hip and knee arthroplasty provided individuals at greatest risk of severe post-operative anaemia can be identified. METHODS AND MATERIALS: Patients undergoing THA, TKA, or UKA between 2011 and 2018 were included. Outcomes were post-operative Hb below 70 and 80 g/L, and peri-operative blood transfusion. Logistic regression assessed the association between pre-operative Hb and each outcome. Decision curve analysis compared strategies for selecting patients for G&S and post-operative Hb measurement. RESULTS: 10 015 THA, TKA and UKA procedures were performed in 8582 patients. The incidence of blood transfusion (4.5%) decreased during the study. Using procedure specific Hb thresholds to select patients for pre-operative G&S and post-operative Hb testing had a greater net benefit than selecting all patients, no patients, or patients with pre-operative anaemia. CONCLUSIONS: Pre-operative G&S and post-operative Hb measurement may not be indicated for UKA or TKA when adopting restrictive transfusion thresholds, provided clinicians accept a 0.1% risk of patients developing severe undiagnosed post-operative anaemia (Hb < 70 g/L). The decision to perform these blood tests for THA patients should be based on local institutional data and selection of acceptable risk thresholds.

Preoperative Severe Acute Respiratory Syndrome Coronavirus 2 Polymerase Chain Reaction Test at Between 48 and 72 Hours Preoperatively is Safe for Patients Undergoing Primary and Revision Hip and Knee Arthroplasty: A Multicentre International Study.

BACKGROUND: Patients undergoing lower limb arthroplasty who are severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive at the time of surgery have a high risk of mortality. The National Institute for Health and Clinical Care Excellence and the British Orthopaedic Association advise self-isolation for 14 days preoperatively in patients at a high risk of adverse outcomes due to COVID-19. The aim of the study is to assess whether preoperative polymerase chain reaction (PCR) for SARS-CoV-2 could be performed at between 48 and 72 hours preoperatively with specific advice about minimizing the risk of SARS-CoV-2 restricted to between PCR and admission. METHODS: A multicentre, international, observational cohort study of 1,000 lower limb arthroplasty cases was performed. The dual primary outcomes were 30-day conversion to SARS-CoV-2 positive and 30-day SARS-CoV-2 mortality. Secondary outcomes included 30-day SARS-CoV-2 morbidity. RESULTS: Of the 1,000 cases, 935 (94%) had a PCR between 48 and 72 hours preoperatively. All cases were admitted to and had surgery through a COVID-free pathway. Primary knee arthroplasty was performed in 41% of cases, primary hip arthroplasty in 40%, revision knee arthroplasty in 11%, and revision hip arthroplasty in 9%. Six percent of operations were emergency operations. No cases of SARS-CoV-2 were identified within the first 30 days. CONCLUSION: Preoperative SARS-CoV-2 PCR test between 48 and 72 hours preoperatively with advice about minimizing the risk of SARS-CoV-2 restricted to between PCR and admission in conjunction with a COVID-free pathway is safe for patients undergoing primary and revision hip and knee arthroplasty. Preoperative SARS-CoV-2 PCR test alone may be safe but further adequately powered studies are required. This information is important for shared decision making with patients during the current pandemic.

Investigating the impact of bank branch closures on access to financial services in the early stages of the COVID-19 pandemic.

There is a longstanding policy interest in understanding the impacts of changes in access to public and private services in rural areas. To date much of the empirical analysis concerning changing patterns of accessibility has been predicated on assumptions regarding the mode of transport used to access such facilities. The availability of new and open sources of data, and the increasing sophistication of spatial analytical tools, has enabled alternative transportation modes to be included when investigating the impact of service changes. In this study a nationwide analysis of changes in public transport provision and bank closures has enabled the identification of those parts of Wales that were disproportionally impacted by the loss of financial services during the early years of the COVID-19 pandemic. Drawing on local scenarios which show the combined impact of such changes, the findings demonstrate how temporal variations in accessibility can be used to examine potential patterns of exclusion that arise from the loss of key services. We conclude by suggesting that any assessment of changes in accessibility needs a holistic approach that considers changes in the transport infrastructure alongside other facets of service provision to understand the full impact of such closures on rural communities.

Optimized medial unicompartmental knee arthroplasty outcome: learning from 20 years of propensity score matched registry data.

BACKGROUND AND PURPOSE: Unicompartmental knee arthroplasty (UKA) has increased in use. We investigated changes to UKA revision risk over the last 20 years compared with total knee arthroplasty (TKA), examined external and patient factors for correlation to UKA revision risk, and described the survival probability for current UKA and TKA practice. PATIENTS AND METHODS: All knee arthroplasties reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were linked to the National Patient Register and the Civil Registration System for comorbidity, emigration, and mortality information. All primary UKA and TKA patients with primary osteoarthritis were included and propensity score matched 4 TKAs to 1 UKA. Revision and mortality were analyzed using competing risk cox regression with a shared gamma frailty component. RESULTS: The matched cohort included 48,195 primary knee arthroplasties (9,639 UKAs). From 1997-2001 to 2012-2017 the 3-year hazard ratio decreased from 5.5 (95% CI 2.7-11) to 1.5 (CI 1.2-1.8) due to increased UKA survival. Cementless fixation, a high percentage usage of UKA, and increased surgical volume decreased UKA revision risk, and increased in occurrence parallel to the decreasing revision risks. Current UKA practice using cementless fixation at a high usage unit has a 3-year implant survival of 96% (CI 97-95), 1.1% lower than current TKA practice. INTERPRETATION: UKA revision risk has decreased over the last 20 years, nearing that of TKA surgery. High usage rates, surgical volume, and the use of cementless fixation have increased during the study and were associated with decreased UKA revision risks.

Interpretation threshold values for the Oxford Knee Score in patients undergoing unicompartmental knee arthroplasty.

BACKGROUND AND PURPOSE: Developing meaningful thresholds for the Oxford Knee Score (OKS) advances its clinical use. We determined the minimal important change (MIC), patient acceptable symptom state (PASS), and treatment failure (TF) values as meaningful thresholds for the OKS at 3-, 12-, and 24-month follow-up in patients undergoing unicompartmental knee arthroplasty (UKA). PATIENTS AND METHODS: This is a cohort study with data from patients undergoing UKA collected at a hospital in Denmark between February 2016 and September 2021. The OKS was completed preoperatively and at 3, 12, and 24 months postoperatively. Interpretation threshold values were calculated with the anchor-based adjusted predictive modeling method. Non-parametric bootstrapping was used to derive 95% confidence intervals (CI). RESULTS: Complete 3-, 12-, and 24-month postoperative data was obtained for 331 of 423 (78%), 340 of 479 (71%), and 235 of 338 (70%) patients, median age of 68-69 years (58-59% females). Adjusted OKS MIC values were 4.7 (CI 3.3-6.0), 7.1 (CI 5.2-8.6), and 5.4 (CI 3.4- 7.3), adjusted OKS PASS values were 28.9 (CI 27.6-30.3), 32.7 (CI 31.5-33.9), and 31.3 (CI 29.1-33.3), and adjusted OKS TF values were 24.4 (CI 20.7-27.4), 29.3 (CI 27.3-31.1), and 28.5 (CI 26.0-30.5) at 3, 12, and 24 months postoperatively, respectively. All values statistically significantly increased from 3 to 12 months but not from 12 to 24 months. INTERPRETATION: The UKA-specific measurement properties and clinical thresholds for the OKS can improve the interpretation of UKA outcome and assist quality assessment in institutional and national registries.

Patient beliefs and perceptions play a crucial role in the decision-making process when managing a meniscal tear. A qualitative systematic review of the literature.

INTRODUCTION: There has been an increase in research on the effectiveness of treatment options for the management of meniscal tears. However, there is very little evidence about the patient experiences of meniscal tears. AIM: To summarise the available qualitative evidence on patients' experiences and expectations of meniscal tears. METHOD: A search of EMBASE, Medline, Sociofile and Web of Science up to November 2020 was performed to identify studies reporting patient experiences of meniscal tears. Studies were critically appraised using the CASP (Critical Appraisal Skills Program) checklist, and a meta-synthesis was performed to generate third-order constructs (new themes). RESULTS: Two studies reporting semi-structured interviews from 34 participants (24 male; 10 female) were included. The mean interview length ranged from 16 to 45 min. Five themes were generated: (1) the imaging (MRI) results are a key driver in the decision-making process, (2) surgery is perceived to be the definitive and quicker approach, (3) physiotherapy and exercise is a slower approach which brought success over time, (4) patient perceptions and preferences are important in the clinical decision-making process and, (5) the impact on patient lives is a huge driver in seeking care and treatment decisions. CONCLUSION: This is the first study to summarise the qualitative evidence on patient experiences with meniscal tears. The themes generated demonstrate the importance of patient perceptions of MRI findings and timing of treatment success as important factors in the decision-making process. This study demonstrates the need to strengthen our understanding of patients' experiences of meniscal tears.