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With two thirds of the world's population having no access to safe and affordable surgery, a major report published today in The Lancet highlights the urgent need to invest resources in improving surgical care globally.
An Integrated Education and Exercise Programme for Tamil People With Osteoarthritis Knee
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Osteoarthritis knee (OA knee) is a chronic joint condition associated with pain, disability and reduced quality of life. Guidelines recommend self‐management, patient education, behavioural support and tailored exercise as core components of non‐surgical treatment.</jats:p></jats:sec><jats:sec><jats:title>Purpose</jats:title><jats:p>To develop and evaluate an OA knee patient education booklet and a physiotherapist‐led integrated programme involving the core components of non‐surgical care to improve clinical outcomes in Tamil‐speaking people with OA knee of Tamil Nadu state (Population 72.1 million, 2011 census), India.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A patient education booklet was developed through an iterative process and evaluated in 50 patients, carers, and physiotherapists. The impact of the integrated programme on knee pain, function, physical performance, and adherence was assessed at six weeks and during a follow‐up at six months.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The Tamil booklet was easy to read, useful and relevant. 31 patients (26 women; 5 men, average age 60.4 years) took part in the integrated programme. Improvements in pain, function and performance measures were statistically significant and clinically meaningful. The majority of them found the programme useful and satisfactory and reported that their condition improved. There were no adverse events.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our Tamil OA knee education booklet was deemed relevant and useful. The integrated education and exercise programme was feasible and acceptable and our findings provided preliminary evidence on its clinical benefits in people with OA knee.</jats:p></jats:sec>
Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death.
Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness.
Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes.
The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.
Thalamic deep brain stimulation for central poststroke pain syndrome: an international multicenter study.
OBJECTIVE: The effectiveness and optimal stimulation site of deep brain stimulation (DBS) for central poststroke pain (CPSP) remain elusive. The objective of this retrospective international multicenter study was to assess clinical as well as neuroimaging-based predictors of long-term outcomes after DBS for CPSP. METHODS: The authors analyzed patient-based clinical and neuroimaging data of previously published and unpublished cohorts from 6 international DBS centers. DBS leads were reconstructed and normalized. A stimulation map was constructed on the basis of individual stimulation settings and associated outcomes. Furthermore, the authors projected the individual segmented stroke lesions and volumes of tissue activated (VTAs) of the stimulating electrode onto a normalized human connectome to obtain the connectivity profiles of the individual lesions and VTAs. RESULTS: The authors analyzed the data of 54 patients, of whom 15 were excluded from the final analysis due to a lack of imaging data. Among the remaining 39 patients from 6 different cohorts, the authors found 14 (35.9%) responders who were defined by pain relief of at least 50% at 12-month follow-up. Stimulation mapping identified areas in the posterior limb of the internal capsule, the sensorimotor thalamus, and the medial and intralaminar thalamus as effective for pain reduction. Baseline characteristics did not differ between responders and nonresponders. The stimulation sites of the responders showed significantly reduced structural connectivity to the sensory areas of the cerebral cortex compared to nonresponders. CONCLUSIONS: This comprehensive, multicenter analysis corroborates the efficacy of DBS in treating CPSP for a relevant number of patients. The posterior limb of the internal capsule and the sensorimotor thalamus emerged as potential stimulation sweet spots. The difference in structural connectivity between responders and nonresponders may constitute a biomarker of effective stimulation that can help guide surgical planning in future well-designed prospective trials.
Development of the rehabilitation interventions for people with an acute patellar dislocation in the Physiotherapy Rehabilitation Post Patellar Dislocation (PRePPeD) pilot randomized controlled trial.
AIMS: To develop the rehabilitation interventions for people with an acute patellar dislocation in the Physiotherapy Rehabilitation Post Patellar Dislocation (PRePPeD) pilot randomized controlled trial (RCT), and to describe how these interventions are delivered. METHODS: We developed the interventions drawing on a range of established intervention development approaches and frameworks. We selected intervention components after reviewing the existing evidence, clinical guidelines, UK NHS practice, and relevant scientific theory. We then created early versions of the interventions, and discussed these with clinical experts and patient and public partners. We finalized the interventions considering their feedback, findings from our preliminary study, and what would be acceptable and deliverable in the UK NHS. RESULTS: Upon randomization, all participants receive a workbook containing advice and initial exercises to implement before their first physiotherapy session. Self-managed rehabilitation then involves a single one-to-one session with a physiotherapist who provides advice, introduces a structured home exercise programme, and uses strategies to support exercise adherence. Participants then continue their recovery independently. Supervised rehabilitation involves four to six one-to-one physiotherapy sessions over a maximum of six months. Physiotherapists also provide advice, prescribe home exercise, and use exercise adherence strategies. Routine follow-up sessions enable physiotherapists to reassess participants and tailor the advice and exercises accordingly. CONCLUSION: The interventions were developed and are currently being assessed in the PRePPeD pilot RCT. This will determine whether a full-scale RCT comparing these interventions is feasible. Results are anticipated in Summer 2025.
The burden of hand trauma surgery on primary care in the United Kingdom: a nation-wide analysis of antibiotic and opioid prescriptions.
Although surgical site infection (SSI) risk after hand trauma surgery is around 5%, the severity of these infections is not known. The risk of superficial SSI in a cohort study was evaluated using NHS UK-wide primary care records (n = 641,223), using the Clinical Practice Research Datalink GOLD database. Within this cohort, a subcohort of those who had undergone a hand surgery operation for trauma were identified (n = 3,088). Antibiotic and analgesic prescriptions were analysed at 30 and 90 days postoperatively. By 30 days, 6.2% had been prescribed antibiotics appropriate for SSI, rising to 14.4% (CI [13.2 to 15.8]) by 90 days. By 30 days, 10% had been prescribed opioid analgaesia and by 90 days this had increased to 13.8%. Antibiotics prescriptions for SSI in primary care are substantially higher than the NICE estimate for SSI overall and the expected risk in hand trauma. The implications of this study are that many patients are receiving treatment for SSI in primary care and may be in more pain, for longer, than we expect. Further exploration of this is warranted and future research in hand trauma surgery should capture adverse events occurring outside of the hospital environment.Level of evidence: II.
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement.
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.
T cell phenotypes in COVID-19 - a living review.
COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.
2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.
OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.
Microneedles in diagnostic, treatment and theranostics: An advancement in minimally-invasive delivery system.
Microneedle (MN) technology plays an important role in biomedical engineering for their less intrusive access to the skin due to minimally or painless penetration, enhancement of drug permeability, improvement of detectability of biomolecules in the epidermal and dermal layers with therapeutic efficacy and safety. Furthermore, MNs possess some major disadvantages like difficulty in scale-up technique, variation in drug delivery pattern with respect to external environment of skin, blockage of arrays due to dermal tissues, induction of inflammation or allergy at the site of administration and restriction of dosing range based on the size of active. Additionally, microneedle acts as a transdermal theranostic device for monitoring the physiological parameters in clinical studies. The investigation of drug transfer mechanisms through microneedles includes coat and poke, poke and flow, poke and patch and poke and release method. This review article discusses different categories of microneedles with fabrication methods such as photolithography, laser cutting, 3D printing, etc. in therapeutic applications for treating cancer, diabetes, arthritis, obesity, neurological disorders, and glaucoma. Biosensing devices based on microneedles may detect target analytes directly in the interstitial fluid by penetrating the stratum corneum of the skin and thus microneedles-based devices can be considered as a single tool in diagnostic sensing and therapeutic administration of drugs inside the body. Moreover, the clinical status and commercial availability of microneedle devices are discussed in this review article to offer new insights to researchers and scientists. Continuous monitoring particularly for the determination of blood glucose concentration is one of the most important requirements for the development of next-generation healthcare devices. The aim of this review article focuses mainly on the theranostic applications of microneedles in various medical conditions such as malaria, glaucoma, cancer, etc.
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
The immune-epithelial-stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD intestinal biopsy samples. Here we show that in CD, epithelial populations shifted toward a progenitor state, with interferon-driven transcriptional responses, and perturbation of secretory and enteroendocrine populations. Mucosal T cells showed numeric and functional changes in regulatory and follicular helper-like CD4+ T cells, intraepithelial lymphocytes, CD8+ and γδ T cell subsets, with skewed T cell antigen receptor repertoires. Mucosal changes remained detectable despite treatment, representing a persistent immune-epithelial 'scar'. Spatial transcriptomics defined transcriptional niches beyond those captured in conventional histological scores, including CD-specific lymphoid aggregates containing T cell-B cell interactions. Receptor-ligand spatial analyses integrated with disease susceptibility gene expression defined networks of altered chemokine and morphogen signaling, and provide potential therapeutic targets for CD prevention and treatment.
FRCS Trauma and Orthopaedics Viva
Based on the highly successful Oxford revision course, this book helps candidates prepare for the viva section of the FRCS Trauma and Orthopaedics exam.
Clinical and cost-effectiveness of a personalised guided consultation versus usual physiotherapy care in people presenting with shoulder pain: a protocol for the PANDA-S cluster randomised controlled trial and process evaluation.
INTRODUCTION: Musculoskeletal shoulder pain is a common reason for people to be treated in physiotherapy services, but diagnosis can be difficult and often does not guide treatment or predict outcome. People with shoulder pain cite a need for clear information, and timely, tailored consultations for their pain. This trial will evaluate the introduction of a personalised guided consultation to help physiotherapists manage care for individuals with shoulder pain. METHODS AND ANALYSIS: This is a cluster randomised controlled trial to evaluate the clinical and cost-effectiveness of introducing a personalised guided consultation compared with usual UK NHS physiotherapy care. Physiotherapy services (n=16) will be randomised in a 1:1 ratio to either intervention (physiotherapy training package and personalised guided consultation incorporating a new prognostic tool) or control (usual care); 832 participants (416 in each arm) identified from participating physiotherapy service waiting lists aged 18 years or over with shoulder pain will be enrolled. Follow-up will occur at 3 time points: 6 weeks, 6 months and 12 months. The primary outcome will be the Shoulder Pain and Disability Index (SPADI) score over 12 months. Secondary outcomes include global perceived change of the shoulder condition, sleep, work absence and the impact of shoulder pain on work performance, healthcare utilisation and health-related quality of life (using EuroQol 5 Dimension 5 Level (EQ-5D-5L)). A multimethod process evaluation will investigate views and experiences of participants and physiotherapists, assess uptake, facilitators and barriers to delivery, and changes in factors assumed to explain intervention outcomes. Primary analysis of effectiveness will be by intention-to-treat, and a health economic evaluation will assess cost-utility of introducing the personalised consultation. ETHICS AND DISSEMINATION: The trial received ethics approval from the Yorkshire & The Humber (South Yorkshire) Research Ethics Committee (REC reference: 23/YH/0070). Findings will be shared through journal publications, media outlets and conference presentations. Supported by patient contributors and clinical advisors, we will communicate findings through a designated website, networks, newsletters, leaflets and in the participating physiotherapy services. TRIAL REGISTRATION NUMBER: ISRCTN45377604.
A review of the statistical analysis of randomised controlled trials conducted within OCTRU.
INTRODUCTION: Despite a proliferation of statistical methodologies and developments within randomised controlled trials (RCTs) in recent decades, it is unclear which approaches are being implemented in practice. Oxford Clinical Trials Research Unit (OCTRU) is a UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Unit (CTU) that has been operational since 2013 based in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford. We performed a review of all published RCTs conducted within OCTRU, with particular emphasis on trial methodology, statistical study design and statistical analysis. METHODS: Studies were considered eligible if they were: RCTs conducted by OCTRU, have been completed and disseminated their primary results. Studies were ineligible if they were: a pilot or feasibility trial, a simulation study, a secondary analysis of an existing RCT, or a phase I trial. Phase II trials were considered if they were randomised. We performed double data extraction of all fields for all eligible trials. General trial information, such as primary disease area, main funding source, sample size, trial design and analysis information (e.g. number of study outcomes and analyses performed), were extracted and summarised. An analysis was defined as any time a statistical model was fit or a corresponding statistical test (e.g. χ2 test) and/or estimation of a parameter was performed. RESULTS: Of the 142 OCTRU studies registered & funded (as of June 2023), 70 were completed and written up and 27 were eligible at the time of this review. The rest were ongoing or found to be ineligible. Included studies were published between 2014 and 2023, the majority in the last 5 years (20/27, 74% published between 2020 and 2023). All trials were multi-centre, prospectively designed and referred to both a study protocol and sample size justification (usually a power calculation) in their published results. Most included studies had elements of what could be referred to as a 'standard' RCT; used a parallel group design (93%), powered with superiority question (26/27, 96%), had two randomised groups (23/27, 85%) or used an equal allocation ratio (25/27, 93%). The median sample size was 451 (interquartile range: 238-836). The median total number of analyses performed was 22 (Interquartile range: 14-30) with the most analyses performed within a single trial being 69. Eighty-one per cent (22/27) of trials had a primary outcome with either binary or continuous data. Linear mixed effects, linear regression or logistic regression was used as the primary analysis model in 74% of the 27 trials. All trials that included at least one analysis (26/27) featured at least one additional analysis on the primary outcome, the most popular additional analyses were on an alternative population (for example a per-protocol population), occurring in 20/27, 74% of all trials, or a subgroup (18/27, 67%)). CONCLUSIONS: This review summarises RCTs conducted by one academic UKCRC-registered CTU with a focus on the trial design and statistical analysis. We found most RCTs adopted what could be considered a 'standard' design, using appropriate, but not complex, analysis methods. Consideration of variation in practice across other groups, both academic and commercial, through a larger review would allow systematic exploration of methodological differences, less common study design usage, and would enable a fuller understanding of practice, outcomes, and methods used in different clinical areas and contexts.
Ethnic disparities in COVID-19 mortality and cardiovascular disease in England and Wales between 2020-2022
Previous studies reported higher COVID-19 mortality risk among certain ethnic groups, but data on ethnic disparities in COVID-19-related cardiovascular disease (CVD) were lacking. We estimated age-standardised incidence rates and adjusted hazard ratios for 28-day mortality and 30-day CVD for individual ethnicity groups from England and Wales, using linked health and administrative data. We studied 6-level census-based ethnicity group classification, 10-level classification (only for Wales), and 19-level classification as well as any ethnicity sub-groups comprising >1000 individuals each (only for England). COVID-19 28-day mortality and 30-day CVD risk was increased in most non-White ethnic groups in England and Asian population in Wales between 23rd January 2020 and 1st April 2022. English data show mortality decreased during the Omicron variant's dominance, whilst CVD risk [95% confidence interval] remained elevated for certain ethnic groups when compared to White populations (January-April 2022): by 120% [28-280%] in White and Asian men and 58% [32-90%] in Pakistan men, as compared to White British men; and by 75% [13-172%] in Bangladeshi women, 55% [19-102%] in Caribbean women, and 82% [31-153%] in Any Other Ethnic Group women, as compared to White British women. Ethnically diverse populations remained disproportionately affected by CVD throughout and beyond the COVID-19 pandemic.