Biomarkers in prosthetic joint infection & the molecular role of antibiotics in soft tissue repair

Background: In Orthopaedic surgery the diagnosis, treatment and prevention of infection are key to successful patient outcomes, this has led to the increased use of antibiotics. Infection following implant or graft surgery has high levels of patient morbidity and associated costs of treatment. Antibiotic prophylaxis coupled with early accurate diagnosis can improve outcomes. Currently, implant related infection is diagnosed using diagnostic algorithms which combine numerous blood and tissue investigations, however, there is no single test available to rule infection in or out and reliance on clinical judgement is still at the forefront. Novel gene sequencing techniques are coming to the forefront of diagnostics across all medical specialties and here I present a pilot study of the use of a new sequencing method and diagnostic rationale - looking at the patient’s own immune response to identify the presence of implant infection. Antibiotic prophylaxis, usually given intravenously at the time of surgery has led to a significant reduction in implant infection. Developing more localised ways to administer this prophylaxis led to the introduction of an antibiotic ‘wrap’ - whereby tissue graft is wrapped in antibiotic solution prior to insertion. This method has significantly reduced infection rates following graft surgery however, it remains unknown if this antibiotic has any adverse molecular or biomechanical effect on the graft tissue, an issue this work aims to address. Key Findings: Tissue and blood from patients undergoing orthopaedic implant related revision surgery was sequenced on a novel immune gene panel. From this, patterns of gene expression were identified in tissue which defined the infected from the aseptic control cohort. Furthermore, the immune gene response was able to characterise different time points of infection, identifying signatures for acute infection and chronic infection. Sequencing blood samples from the same cohort I was able to establish a gene signature which provided genus level bacterial identification, previously only provided following microbiology culture. Vancomycin antibiotic treatment of tendon graft tissue, used in anterior cruciate ligament reconstruction, was not associated with an increase in apoptotic gene or protein expression. Furthermore, no consistent changes were seen in tendon matrix gene or protein expression. I did identify a consistent trend of reduced levels of inflammatory cytokines following vancomycin compared with control conditions. Conclusions: Novel gene sequencing techniques and a ‘switched’ diagnostic strategy have shown promise in diagnosing and categorising infection in orthopaedic implant surgery. Antibiotic ‘wrap’ of the hamstring graft in ACL surgery may induce a beneficial homeostatic molecular environment, via a reduction in inflammatory cytokines

Digital communication between clinician and patient in General Practice and the impact on marginalised groups : a realist review

Background Increasingly, the NHS is embracing the use of digital communication technology for communication between clinicians and patients. Policymakers deem digital clinical communication as presenting a solution to the capacity issues currently faced by general practice. There is some concern that these technologies may exacerbate existing inequalities in accessing health care. It is not known what impact they may have on groups who are already marginalised in their ability to access general practice. Aim To assess the potential impact of the availability of digital clinician–patient communication on marginalised groups’ access to general practice in the UK. Design and setting Realist review in general practice. Method A four-step realist review process was used: to define the scope of the review; to search for and scrutinise evidence; to extract and synthesise evidence; and to develop a narrative, including hypotheses. Results Digital communication has the potential to overcome the following barriers for marginalised groups: practical access issues, previous negative experiences with healthcare service/staff, and stigmatising reactions from staff and other patients. It may reduce patient-related barriers by offering anonymity and offers advantages to patients who require an interpreter. It does not impact on inability to communicate with healthcare professionals or on a lack of candidacy. It is likely to work best in the context of a pre-existing clinician–patient relationship. Conclusion Digital communication technology offers increased opportunities for marginalised groups to access health care. However, it cannot remove all barriers to care for these groups. It is likely that they will remain disadvantaged relative to other population groups after their introduction

Treatment of periscapular tendinopathy with radiofrequency coblation: a case report

Overuse injuries of the tendon – ‘tendinopathy’ – account for 30%–50% of all sporting injuries and a high proportion of orthopaedic referrals from primary care physicians. Tendinopathies often have a multifactorial aetiology and injury can be due to a combination of both acute and chronic trauma which contributes to loss of tissue integrity and eventual rupture. Our incomplete understanding of the mechanisms surrounding tendon pathophysiology continues to cause difficulties in treatments beyond loading regimes which can be unsuccessful in up to 30% of cases. We describe an uncommon case of tendinopathy affecting the periscapular muscle/tendon unit in a 35-year-old female with persistent pain around the inferior posterior pole of her right scapula. Magnetic resonance imaging findings confirmed oedema of the muscles around the inferior scapular margin in keeping with enthesopathy/tendinopathy and she was treated with radiofrequency coblation to the area. This case highlights radiofrequency ablation as a surgical option should non-operative treatments fail in the rare diagnosis of periscapular tendinopathy

Diurnal and Seasonal Solar Induced Chlorophyll Fluorescence and Photosynthesis in a Boreal Scots Pine Canopy

Solar induced chlorophyll fluorescence has been shown to be increasingly an useful proxy for the estimation of gross primary productivity (GPP), at a range of spatial scales. Here, we explore the seasonality in a continuous time series of canopy solar induced fluorescence (hereafter SiF) and its relation to canopy gross primary production (GPP), canopy light use efficiency (LUE), and direct estimates of leaf level photochemical efficiency in an evergreen canopy. SiF was calculated using infilling in two bands from the incoming and reflected radiance using a pair of Ocean Optics USB2000+ spectrometers operated in a dual field of view mode, sampling at a 30 min time step using custom written automated software, from early spring through until autumn in 2011. The optical system was mounted on a tower of 18 m height adjacent to an eddy covariance system, to observe a boreal forest ecosystem dominated by Scots pine. (Pinus sylvestris) A Walz MONITORING-PAM, multi fluorimeter system, was simultaneously mounted within the canopy adjacent to the footprint sampled by the optical system. Following correction of the SiF data for O2 and structural effects, SiF, SiF yield, LUE, the photochemicsl reflectance index (PRI), and the normalized difference vegetation index (NDVI) exhibited a seasonal pattern that followed GPP sampled by the eddy covariance system. Due to the complexities of solar azimuth and zenith angle (SZA) over the season on the SiF signal, correlations between SiF, SiF yield, GPP, and LUE were assessed on SZ

Improving health outcome for young people with long term conditions: The role of digital communication in current and future patient-clinician communication for NHS providers of specialist clinical services for young people receiving specialist clinical services:LYNC study protocol.

Background: Young people living with long term conditions are vulnerable to health service disengagement. This endangers their long term health. Studies report requests for digital forms of communication - email, text, social media - with their health care team. Digital clinical communication is troublesome for the UK NHS. Aim: To present the research protocol for evaluating the impacts and outcomes of digital clinical communications for young people living with long term conditions and provide critical analysis of their use, monitoring and evaluation by NHS providers. Methods: The research involves: 1) Patient and Public Involvement activities with 16-24 year olds with and without long term health conditions; 2) six literature reviews; 3) case studies – the main empirical part of the study – and 4) synthesis and a consensus meeting. Case studies use a mixed methods design. Interviews and non-participant observation of practitioners and patients communicating in up to 20 specialist clinical settings will be combined with data, aggregated at the case level (non-identifiable patient data), on a range of clinical outcomes meaningful within the case and across cases. We will describe the use of digital clinical communication from the perspective of patients, clinical staff, support staff and managers, interviewing up to 15 young people and 15 staff per case study. Outcome data includes emergency admissions, A&E attendance and DNA rates. Case studies will be analysed to understand impacts of digital clinical communication on patient health outcomes, health care costs and consumption, ethics and patient safety

Exploring the experiences and preferences of South Asian patients' of primary care in England since COVID‐19

Introduction: Remote (digital and/or telephone) access and consultation models are being driven by national policy with the goal being that the National Health Service operate on a remote‐first (digital‐first) basis by 2029. Previous research has suggested that remote methods of access to care and consulting may act to widen health inequalities for certain patients and/or groups such as those from ethnic minorities. South Asian (SA) patients comprise the largest ethnic minority group in England. Understanding the experiences and needs of this group is critical to ensuring that general practice can deliver equitable, quality health care. Methods: Qualitative study. 37 participants (from Indian, Pakistani and/or Bangladeshi background) were recruited to take part in either in‐person preferred language focus groups or remote semistructured interviews in the English language. Thematic analysis was conducted to identify themes in the qualitative data. Findings: Three major interlinked themes were identified: (1) reduced access, (2) reduced patient choice and (3) quality and safety concerns. The findings highlight access issues split by (i) general issues with appointment access via any remote means and (ii) specific issues related to language barriers creating additional barriers to access and care. Some patients valued the convenience of remote access but also raised concerns regarding appointment availability and reduced patient choice. Face‐to‐face consultations were preferable but less available. The findings underscore how participants perceived remote care to be of lesser quality and less safe. Concerns were greatest for those with limited English proficiency (LEP), with the removal of non‐verbal aspects of communication and ‘hands‐on’ care leading to perceptions of reduced psycho‐social safety. Conclusion: SA patients' experiences of remote‐led primary care access and care delivery were negative with only a minority viewing it positively and for certain limited scenarios. Face‐to‐face models of care remain the preferred mode of consultation, particularly for those with LEP. Hybrid models of access offer patients the greatest choice, and are likely to meet the varying needs of the South‐Asian patient population going forwards. The remote first approach to primary care may be achievable as a service ideal, but its limitations need to be recognised and accounted for to ensure that primary care can be an equitable service, both now and in the future. Public Contribution: Members of the public were involved in all phases of research in the study. This included co‐working in partnership throughout the study including, reviewing patient‐facing documents, recruiting participants, data facilitation, translation work, interpretation of the data and co‐authors on this manuscript. The key to the success of our study was collaborative teamwork, which involved experienced members of the public with SA cultural knowledge working together with and integral to the research team for all components

Vancomycin wrap for anterior cruciate ligament surgery

Background: The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft. Purpose: To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR. Study Design: Controlled laboratory study. Methods: Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression. Results: Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05). Conclusion: Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment. Clinical Relevance: Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

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Mode of access: Internet

Multiscale remote sensing of plant physiology and carbon uptake

This study investigated the use of optical remote sensing for estimating leaf and canopy scale light use efficiency (LUE) and carbon exchange. In addition, a new leaf level model capable of predicting dynamic changes in apparent reflectance due to chlorophyll fluorescence was developed. A leaf level study was conducted to assess the applicability of passive remote sensing as a tool to measure the reduction, and the subsequent recovery, of photosynthetic efficiency during the weeks following transplantation. Spectral data were collected on newly planted saplings for a period of 8 weeks, as well as gas exchange measurements of LUE and PAM fluorescence measurements. A set of spectral indices, including the Photochemical Reflectance Index (PRI), were calculated from the reflectance measurements. A marked depression in photosynthetic rate occurred in the weeks after outplanting followed by a gradual increase, with recovery occurring in the later stages of the experimental period. As with photosynthetic rate, there was a marked trend in PRI values over the study period but no trend was observed in chlorophyll based indices. The study demonstrated that hyperspectral remote sensing has the potential to be a useful tool in the detection and monitoring of the dynamic effects of transplant shock. Relationships between hyperspectral reflectance indices, airborne carbon exchange measurements and satellite observations of ground cover were then explored across a heterogeneous Arctic landscape. Measurements were collected during August 2008, using the University of Edinburgh’s research aircraft, from an Arctic forest tundra zone in northern Finland as part of the Arctic Biosphere Atmosphere Coupling at Multiple Scales (ABACUS) study. Surface fluxes of CO2 were calculated using the eddy covariance method from airborne data that were collected from the same platform as hyperspectral reflectance measurements. Airborne CO2 fluxes were compared to MODIS vegetation indices. In addition, LUE was estimated from airborne flux data and compared to airborne measurements of PRI. There were no significant relationships between MODIS vegetation indices and airborne flux observations. There were weak to moderate (R2 = 0.4 in both cases) correlations between PRI and LUE and between PRI and incident radiation. A new coupled physiological radiative transfer model that predicts changes in the apparent reflectance of a leaf, due to chlorophyll fluorescence, was developed. The model relates a physically observable quantity, chlorophyll fluorescence, to the sub leaf level processes that cause the emission. An understanding of the dynamics of the processes that control fluorescence emission on multiple timescales should aid in the interpretation of this complex signal. A Markov Chain Monte Carlo (MCMC) algorithm was used to optimise biochemical model parameters by fitting model simulations of transient chlorophyll fluorescence to measured reflectance spectra. The model was then validated against an independent data set. The model was developed as a precursor to a full canopy scheme. To scale to the canopy and to use the model on trans-seasonal time scales, the effects of temperature and photoinhibition on the model biochemistry needs to be taken into account, and a full canopy radiative transfer scheme, such as FluorMOD, must be developed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo