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Lower limb muscle strength and balance in older adults with a distal radius fracture: a systematic review.
BACKGROUND: Distal radius fractures are common fractures in older adults and associated with increased risk of future functional decline and hip fracture. Whether lower limb muscle strength and balance are impaired in this patient population is uncertain. To help inform rehabilitation requirements, this systematic review aimed to compare lower limb muscle strength and balance between older adults with a distal radius fracture with matched controls, and to synthesise lower limb muscle strength and balance outcomes in older adults with a distal radius fracture. METHODS: We searched Embase, MEDLINE, and CINAHL (1990 to 25 May 2022) for randomised and non-randomised controlled clinical trials and observational studies that measured lower limb muscle strength and/or balance using instrumented measurements or validated tests, in adults aged ≥ 50 years enrolled within one year after distal radius fracture. We appraised included observational studies using a modified Newcastle-Ottawa Scale and included randomised controlled trials using the Cochrane risk-of-bias tool. Due to the clinical and methodological heterogeneity in included studies, we synthesised results narratively in tables and text. RESULTS: Nineteen studies (10 case-control studies, five case series, and four randomised controlled trials) of variable methodological quality and including 1835 participants (96% women, mean age 55-73 years, median sample size 82) were included. Twelve included studies (63%) assessed strength using 10 different methods with knee extension strength most commonly assessed (6/12 (50%) studies). Five included case-control studies (50%) assessed lower limb strength. Cases demonstrated impaired strength during functional tests (two studies), but knee extension strength assessment findings were conflicting (three studies). Eighteen included studies (95%) assessed balance using 14 different methods. Single leg balance was most commonly assessed (6/18 (33%) studies). All case-control studies assessed balance with inconsistent findings. CONCLUSION: Compared to controls, there is some evidence that older adults with a distal radius fracture have impaired lower limb muscle strength and balance. A cautious interpretation is required due to inconsistent findings across studies and/or outcome measures. Heterogeneity in control participants' characteristics, study design, study quality, and assessment methods limited synthesis of results. Robust case-control and/or prospective observational studies are needed. REGISTRATION: International prospective register of systematic reviews (date of registration: 02 July 2020, registration identifier: CRD42020196274).
Predictors of Adherence to a Step Count Intervention Following Total Knee Replacement: An Exploratory Cohort Study.
OBJECTIVE: To explore the person-level predictors of adherence to a step count intervention following total knee replacement (TKR). DESIGN: Prospective cohort study, nested within the PATHway trial. METHODS: Participants who had recently undergone TKR were recruited from 3 rehabilitation hospitals in Sydney, Australia, for the main trial. Only data from participants who were randomized to the TKR intervention group were analyzed. Participants in the intervention group (n = 51) received a wearable tracker to monitor the number of steps taken per day. Step count adherence was objectively measured at 3 months as the number of steps completed divided by the number prescribed and multiplied by 100 to express adherence as a percentage. Participants were classified into 4 groups: withdrawal, low adherence (0%-79%), adherent (80%-100%), and >100% adherent. Ordinal logistic regression was used to identify which factors predicted adherence to the prescribed step count. RESULTS: Of the 51 participants enrolled, nine (18% of 51) withdrew from the study before 3 months. Half of participants were classified as >100% adherent (n = 24%, 47%). Ten were classified as low adherence (20%), and 8 participants were classified as adherent (16%). In the univariable model, lower age (OR 0.90; 95% CI 0.83-0.97), higher patient activation (OR 1.03; 95% CI 1.00-1.06), and higher technology self-efficacy (OR 1.03; 95% CI 1.00-1.06) were associated with higher adherence. After adjusting for age in the multivariable model, patient activation and technology self-efficacy were not significant. CONCLUSION: Younger age, higher patient activation, and higher technology self-efficacy were associated with higher adherence to a step count intervention following TKR in the univariable model. Patient activation and technology self-efficacy were not associated with higher adherence following adjustment for age. J Orthop Sports Phys Ther 2022;52(9):620-629. Epub: 9 July 2022. doi:10.2519/jospt.2022.11133.
Microglial depletion increases aggrecan and hyaluronan levels in the diffuse and aggregated extracellular matrix of the mouse brain.
The extracellular matrix (ECM) in the brain can be divided into aggregated ECM, such as perineuronal nets (PNNs) around neurons, and diffuse ECM, which is present throughout the brain parenchyma. Both aggregated and diffuse ECM restrict synaptic plasticity and stabilize neural circuits in the adult brain. Hyaluronan (HA) acts as a scaffold for the brain ECM, and multiple proteoglycans, such as aggrecan, bind to HA to form a macromolecular complex. Recent evidence suggests that microglia, the resident immune cells of the brain, play a crucial role in ECM homeostasis. However, it remains unclear how microglia influence the molecular composition of the ECM. Using a tissue-clearing technique and histochemical analysis, we found that microglial depletion increased the staining intensity of aggrecan and HA in both PNNs and diffuse ECM. Biochemical analyses further confirmed the accumulation of the aggrecan core protein and HA following microglial depletion. Our findings highlight the essential role of microglia in regulating the ECM composition and provide new insights into the mechanisms by which microglia influence neuronal function.
Radiofrequency thalamotomy for tremor outcomes correlate with dentorubrothalamic tract distance.
BACKGROUND: Thalamotomy was the main surgical treatment for medically refractory tremor before deep brain stimulation (DBS). While DBS is now preferred, it has drawbacks such as hardware failure, infection risk, frequent battery replacements, and multiple programming adjustments. Radiofrequency (RF) thalamotomy avoids these issues, can be performed under local anaesthesia, and suits patients in poor health. This study examines long-term outcomes of RF thalamotomy. METHODS: We reviewed 14 consecutive RF thalamotomies performed in Oxford from 2016 to 2021. Three patients died from unrelated causes, leaving eight for long-term assessment. We recorded Bain and Findlay (BF) tremor scores, Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Change (CGI-C), Patient's Global Impression of Change (PGI-C), and Efficacy Index (EI). The median follow-up was 39 months (range 12-126). Post-operative tractography was correlated with clinical outcomes. RESULTS: Six patients had essential tremor and eight had Parkinson's disease. Reasons for choosing thalamotomy over DBS included medical comorbidities, patient preference, age, and previous DBS failure. Ten patients (71%) reported significant tremor improvement, with relapse in two after six months. The mean BF tremor score decreased from 16.1 preoperatively to 8.5 postoperatively (p = 0.0043). Adverse events occurred in seven patients (50%), resolving completely in three, partially in three, and persisting in one. Sustained outcomes correlated with a wider distance of residual dentrorubrothalamic tract (DRTT) fibres from the lesion. CONCLUSIONS: RF thalamotomy is an effective long-term treatment for medication-refractory tremor and should be considered for select patients needing unilateral tremor control.
Clinical neurocardiology: defining the value of neuroscience-based cardiovascular therapeutics - 2024 update.
The intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience-based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans. A decade after the inaugural edition, this White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology and pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.
Provision of peri-operative patient blood management strategies in the UK: a national survey of practice.
INTRODUCTION: In UK hospitals, it is unclear how organisational structures are arranged to support effective implementation of peri-operative blood management practice strategies. The aim of this study was to conduct a national survey of organisations to describe local practices of peri-operative patient blood management and infrastructure availability in the UK. METHODS: A series of benchmarking standards was developed using recommendations informed by national standards, relevant literature and an expert panel. Through the Research and Audit Federation of Trainees networks, 143 hospitals were approached to participate. The pre-piloted survey was conducted online between January and February 2023. RESULTS: Responses were received from 123 hospitals across 74 NHS Trusts and health boards. Formal elective anaemia pathways were not reported in 37/123 (30%) sites. There was considerable inter-site variation in interventional thresholds for anaemia and screening tests. A variety of oral iron regimens were reported, from once-daily dosing in 41/85 (48%) sites, to three times a day dosing in 14/85 (16%). Ferric carboxymaltose was the preparation used most frequently at sites that administered intravenous iron (61/113, 54%). There was variation between hospitals and surgical specialties in the use of tranexamic acid with 49/122 (39%) hospitals reporting a policy for the use of peri-operative tranexamic acid. For sites that performed major surgery routinely (irrespective of specialty), 20/112 (18%) included tranexamic acid in operating theatre safety briefings. Point-of-care coagulation testing was available at 62/123 (50%) sites. DISCUSSION: Our findings show considerable heterogeneity in peri-operative patient blood management strategies and supporting infrastructure availability across the UK. There is a pressing need for hospitals to review pathways of care offered to surgical patients and implement national recommendations.
Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants.
BACKGROUND: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase 1 clinical trial of Treg therapy in living donor renal transplantation, the ONE Study (ClinicalTrials.gov: NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression. METHODS: We present 7 years of follow-up data on patients treated with adoptive Treg therapy early post-transplantation who exhibited focal lymphocytic infiltrates on a 9-month protocol biopsy. We phenotyped their adoptively transferred and peripherally circulating Treg compartments using CITE-seq and investigated the focal lymphocytic infiltrates with spatial proteomic and transcriptomic technologies. FINDINGS: Graft survival rates were not significantly different between Treg-treated patients and the control reference group. None of the Treg-treated patients experienced clinical rejection episodes or developed de novo donor-specific antibodies, and three of ten successfully reduced their immunosuppression to tacrolimus monotherapy. All Treg-treated patients who underwent a protocol biopsy 9 months post-transplantation exhibited focal lymphocytic infiltrates. Spatial profiling analysis revealed prominent CD20+ B cell and regulatory (IKZF2, IL10, PD-L1, TIGIT) signatures within cell-therapy-associated immune infiltrates, distinct from the pro-inflammatory myeloid signature associated with rejection biopsies. CONCLUSIONS: We demonstrate for the first time that immune cell infiltrates in transplanted kidneys can occur following adoptive Treg therapy in humans, potentially facilitating within-graft T:B cell interactions that promote local immune regulation. FUNDING: This work was funded by the 7th EU Framework Programme, grant/award no. 260687, and the National Institute for Health Research (NIHR).
Exploiting electronic health records to improve infection management
The main goal of effective infection management is to prescribe antimicrobials with an appropriate spectrum to combat the infecting pathogen and with dosing regimens that are optimally adjusted to the patient’s characteristics to ensure efficacy. This first requires identifying the causative organism(s) and their antimicrobial susceptibilities to target therapy. However, this may be delayed due to the time taken to obtain culture results and then susceptibilities, or inconclusive if culture results are negative or only contaminating organisms are identified. Changing demographics, such as an ageing population and rising obesity rates, complicate dosing regimens, which are often developed from studies in healthy volunteers, leading to possible suboptimal outcomes. The widespread adoption of electronic health records (EHR) offers a major opportunity to refine antimicrobial practices. This thesis aims to exploit electronic health records for improving infection management, focusing particularly on how they can be used to improve antimicrobial prescribing and tracking response to infection. I first evaluated the effectiveness of vancomycin prescribing guidelines at Oxford University Hospitals. The results showed that despite good compliance with the new guidelines (70-80%), the proportion of drug levels within the target range remained suboptimal (~30%). Using the real-world pharmacokinetic data, I developed updated dose recommendations to optimise drug levels, taking into account patient age, weight, and renal function. I then explored how routinely collected clinical parameters could guide treatment decisions in patients presenting with presumed bloodstream infections (BSI; based on having a blood culture taken), particularly when blood culture results are pending or negative. I found that how C-reactive protein and vital signs measurements changed over time after blood was taken for culture (“response trajectories”) were associated with specific pathogen groups and infection sources in individuals with suspected BSI. Distinct patterns of clinical response trajectories were identified: early peaks (day 1 or 2) and typical recovery, slow recovery, a delayed peak (day 6), or persistently low levels. Centile reference charts were created based on the subgroups with “normal” responses to antibiotics as determined by latent class modelling to standardise the assessment of infection progression and treatment response in patients with suspected BSI; these could be used to guide management independently of microbiological test results. Finally, I examined the current clinical antibiotic prescribing patterns for suspected BSI and their association with the dynamics of these clinical parameters. Overall, the thesis demonstrates the potential of EHR as a pivotal tool in enhancing the quality of antimicrobial management in clinical settings. By integrating data from EHR with patient-specific characteristics and real-time clinical responses, more personalised treatment recommendations can be developed to improve outcomes in patients with varying demographics and health profiles.
Transformers and large language models are efficient feature extractors for electronic health record studies.
BACKGROUND: Free-text data is abundant in electronic health records, but challenges in accurate and scalable information extraction mean less specific clinical codes are often used instead. METHODS: We evaluated the efficacy of feature extraction using modern natural language processing methods (NLP) and large language models (LLMs) on 938,150 hospital antibiotic prescriptions from Oxfordshire, UK. Specifically, we investigated inferring the type(s) of infection from a free-text "indication" field, where clinicians state the reason for prescribing antibiotics. Clinical researchers labelled a subset of the 4000 most frequent unique indications (representing 692,310 prescriptions) into 11 categories describing the infection source or clinical syndrome. Various models were then trained to determine the binary presence/absence of these infection types and also any uncertainty expressed by clinicians. RESULTS: We show on separate internal (n = 2000 prescriptions) and external test datasets (n = 2000 prescriptions), a fine-tuned domain-specific Bio+Clinical BERT model performs best across the 11 categories (average F1 score 0.97 and 0.98 respectively) and outperforms traditional regular expression (F1 = 0.71 and 0.74) and n-grams/XGBoost (F1 = 0.86 and 0.84) models. A zero-shot OpenAI GPT4 model matches the performance of traditional NLP models without the need for labelled training data (F1 = 0.71 and 0.86) and a fine-tuned GPT3.5 model achieves similar performance to the fine-tuned BERT-based model (F1 = 0.95 and 0.97). Infection sources obtained from free-text indications reveal specific infection sources 31% more often than ICD-10 codes. CONCLUSIONS: Modern transformer-based models have the potential to be used widely throughout medicine to extract information from structured free-text records, to facilitate better research and patient care.
A 3-week pause versus continued Bruton tyrosine kinase inhibitor use during COVID-19 vaccination in individuals with chronic lymphocytic leukaemia (IMPROVE trial): a randomised, open-label, superiority trial.
BACKGROUND: Chronic lymphocytic leukaemia is the commonest leukaemia and is associated with profound immunosuppression. Bruton tyrosine kinase inhibitors (BTKi) have revolutionised chronic lymphocytic leukaemia management; however, therapy impairs vaccine-induced immunity. We evaluated whether a 3-week pause of BTKi treatment improved spike protein receptor binding domain (RBD) immunity to SARS-CoV-2 booster vaccination while maintaining disease control. METHODS: We performed an open-label, two-arm, parallel-group, randomised trial in secondary-care haematology clinics in 11 UK hospitals. Participants aged 18 years or older, diagnosed with chronic lymphocytic leukaemia, and currently taking BTKi therapy (frontline or relapsed setting) for at least 12 months were eligible. Participants were randomly allocated (1:1, by a centralised computer randomisation program, stratified by BTKi therapy line) to pause BTKi for 3 weeks, starting 6 days before their SARS-CoV-2 vaccination booster date, or to continue therapy as usual. Neither participants nor clinical staff were blinded but laboratory staff were. Intramuscular injection of either original BA.1 or original BA.4/5 bivalent mRNA vaccine (50 μg mRNA-1273 or 30 μg BNT162b2), or 5 μg protein-based Vidprevtyn Beta (Sanofi Pasteur, Lyon, France) were received according to the national vaccination programme schedule. The primary outcome measure was anti-spike-RBD-specific antibody titre 3 weeks after vaccination and analysis performed by intention to treat (as randomly allocated, irrespective of compliance) following trial completion. This trial is registered with ISRCTN, 14197181, and has been completed. FINDINGS: Between Oct 10, 2022, and June 8, 2023, 99 individuals (71 [72%] male and 28 [28%] female, with 89 [90%] of White ethnicity) were randomly allocated to groups pausing (n=50 [51%]) or continuing (n=49 [49%]) their BTKi therapy, and followed up for 12 weeks. At 3 weeks after vaccination, the geometric mean anti-spike-RBD-specific antibody titre was 218·8 U/mL (SD 122·9) in the continue group and 153·4 U/mL (103·2) in the pause group, with geometric mean ratio 1·104 (95% CI 0·565-2·158, p=0·77) using a mixed-effects model. The only serious adverse event during the 12-week follow-up was the death of one participant in the pause group due to COVID-19 infection 2 months after randomisation. INTERPRETATION: Although the study was slightly underpowered, the results suggest that pausing BTKi around the time of vaccination is not beneficial for immunity and should not be recommended in clinical practice. FUNDING: National Institute for Health and Care Research.
Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial
This article consists of a citation of a published article describing research funded by the Efficacy and Mechanism Evaluation programme under project number NIHR134607, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1016/S2213-2600(22)00186-2 Background Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Methods We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (≤25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. Findings Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the continue methotrexate group and 127 in the suspend methotrexate group. Their mean age was 59·1 years, 155 (61%) were female, 130 (51%) had rheumatoid arthritis, and 86 (34%) had psoriasis with or without arthritis. After 4 weeks, the geometric mean S1-RBD antibody titre was 22 750 U/mL (95% CI 19 314-26 796) in the suspend methotrexate group and 10 798 U/mL (8970-12 997) in the continue methotrexate group, with a geometric mean ratio (GMR) of 2·19 (95% CI 1·57-3·04; p<0·0001; mixed-effects model). The increased antibody response in the suspend methotrexate group was consistent across methotrexate dose, administration route, type of immune-mediated inflammatory disease, age, primary vaccination platform, and history of SARS-CoV-2 infection. There were no intervention-related serious adverse events. Interpretation A 2-week interruption of methotrexate treatment for people with immune-mediated inflammatory diseases resulted in enhanced boosting of antibody responses after COVID-19 vaccination. This intervention is simple, low-cost, and easy to implement, and could potentially translate to increased vaccine efficacy and duration of protection for susceptible groups. Funding National Institute for Health and Care Research. Funding This publication was funded by the Efficacy and Mechanism Evaluation programme as a part of award number NIHR134607. This article reports on one component of the research award Vaccine Response On/Off Methotrexate (VROOM): does temporarily suspending methotrexate treatment for two weeks enhance COVID-19 vaccine response? A randomised controlled trial. For more information about this research please view the award page [https://fundingawards.nihr.ac.uk/award/NIHR134607] DOI https://doi.org/10.1016/S2213-2600(22)00186-2
JaxMARL: multi-agent RL environments and algorithms in JAX
Benchmarks play an important role in the development of machine learning algorithms, with reinforcement learning (RL) research having been heavily influenced by the available environments. However, RL environments are traditionally run on the CPU, limiting their scalability with typical academic compute. Recent advancements in JAX have enabled the wider use of hardware acceleration to overcome these computational hurdles, enabling massively parallel RL training pipelines and environments. This is particularly useful for multi-agent reinforcement learning (MARL) research. First of all, multiple agents must be considered at each environment step, adding computational burden, and secondly, the sample complexity is increased due to non-stationarity, decentralised partial observability, or other MARL challenges. In this paper, we present JaxMARL, the first open-source code base that combines ease-of-use with GPU enabled efficiency, and supports a large number of commonly used MARL environments as well as popular baseline algorithms. When considering wall clock time, our experiments show that per-run our JAX-based training pipeline is up to 12500x faster than existing approaches. We also introduce and benchmark SMAX, a vectorised, simplified version of the popular StarCraft Multi-Agent Challenge, which removes the need to run the StarCraft II game engine. This not only enables GPU acceleration, but also provides a more flexible MARL environment, unlocking the potential for self-play, meta-learning, and other future applications in MARL. We provide code at https://github.com/flairox/jaxmarl.
Global clubfoot treatment in 2023: an overview of advances and outcomes.
INTRODUCTION: Approximately 200 000 children are born each year with clubfoot, the majority of whom live in low-income and middle-income countries (LMICs). If untreated, clubfoot causes pain and reduced mobility, leading to activity limitations and disability. The Ponseti method is a highly effective and minimally invasive treatment. This observational study aims to quantify the countries providing clubfoot services and the children receiving treatment in 2023 and compares progress since data were first collected in 2005. METHODS: In January and February 2024, data on clubfoot treatment in 2023 were collected from 70 countries. Informants completed a survey about new cases enrolled, treatment outcomes and health system integration. Data were analysed using descriptive statistics, with adjustments made for duplicates, and included clinic locations, the number and ages of children starting treatment, types of support available and Ministry of Health involvement. We compared coverage trends over time and used a cartogram to visualise the extent of clubfoot programme coverage across countries. RESULTS: Responding countries accounted for 83% of all expected cases in LMICs. There was an increase in enrolment numbers, to 40 382, in 2023. Despite this progress, treatment coverage remained low at approximately 22% across respondent countries. While integration of clubfoot services into national healthcare systems varied widely, strong public-private partnerships in many countries suggest a foundation for sustainable, long-term treatment programmes. However, quality care remained a challenge, with only 67% of children receiving their first foot abduction brace, indicating gaps in ensuring comprehensive treatment necessary for successful clubfoot management. Lingering effects of COVID-19 restrictions include a higher percentage of cases enrolled after 1 year of age. CONCLUSIONS: A larger proportion of children in LMICs received Ponseti treatment in 2023 compared with 2005. However, more work is needed to expand national programmes, build sustainable, high-quality treatment capacity and ensure all children get the care they need to avoid lifelong disability.
Mid-term outcomes of the fixed-bearing lateral Oxford unicompartmental knee arthroplasty.
AIMS: Mixed clinical results have been reported following the use of lateral unicompartmental knee arthroplasty (UKA) in patients with isolated lateral compartment osteoarthritis (OA) of the knee. Although this procedure may be appropriate for use in about 10% of knees needing arthroplasty, it is only used in about 1%. The aim of this study was to determine the medium-term results for the Fixed Lateral Oxford (FLO) UKA. METHODS: We report the clinical results and survival for 305 consecutive FLO UKAs implanted in 279 patients between July 2015 and August 2022. A total of 283 knees (93%) satisfied the recommended surgical indications. The mean age of the patients was 70.8 years (SD 11), their mean BMI was 28.4 kg/m2 (SD 5.4), and 219 (72%) were female. Isolated lateral compartment OA was the indication for 298 operations (98%). The mean follow-up was 4.3 years (1 to 8). The Oxford Knee Score (OKS) was recorded pre- and postoperatively. The revision status of all knees was known. RESULTS: There were four revisions (1%): two were conversions to a total knee arthroplasty (TKA) for instability and progressive OA and two had the addition of a medial UKA for medial compartment OA. Three other UKAs required a reoperation. At the last follow-up, the mean OKS was 40.9 (SD 7.8), a mean increase of 20 points from the preoperative score. The cumulative rate of survival with any reoperation, including revision, as the endpoint, at seven years, was 96% (95% CI 91 to 100), with revision as the endpoint was 98% (95% CI 94 to 100) and with revision to a TKA as the endpoint was 99% (95% CI 96 to 100). No revisions required revision TKA components. When those who underwent surgery for indications which were outside the recommended indications were excluded, there were only two revisions, both with the addition of a medial UKA for progressive OA, resulting in a seven-year cumulative survival with revision as the endpoint of 99% (95% CI 93 to 100). CONCLUSION: This study involved the largest published cohort of fixed-bearing lateral UKAs. The good clinical outcomes and medium-term survival of the FLO UKA, particularly in patients satisfying the recommended indications, suggest that it is an excellent alternative to TKA for the treatment of patients with isolated OA of the lateral compartment of the knee.