Exploring the immunological relevance of pre-transplant donor-specific antibody in intestinal transplantation, with special consideration to the liver.

Despite recent advances that have improved outcomes following intestinal transplantation (ITx), achieving long-term patient survival and rejection-free survival is still challenging. Understanding the relevance of pre-transplant human leukocyte antigen (HLA) donor-specific antibody (DSA) in ITx and the immunomodulatory potential of the liver within the allograft is crucial to providing an accurate assessment of pre-transplant immunological risk, which could influence and improve post-transplant outcomes further. This was the primary objective of this retrospective study of 95 adult ITx transplants which took place at Cambridge University Hospitals (United Kingdom) between 2007 and 2019. Two novel programs were developed and validated to identify DSA (tested by Luminex single antigen beads) in this dataset. Data analysis utilised Kaplan-Meier survival methods, and statistical analysis was performed using log-rank tests and adjusted Cox models. Fifty-four (57%) ITx cases contained a liver, and 36 (38%) were sensitised to HLA. Pre-transplant DSA > 500 mean fluorescent intensity appeared to negatively affect post-ITx patient survival and rejection outcomes. Additionally, liver-inclusive allografts seemed to show particular resistance to HLA class I DSA. Our data hints towards consistency with other ITx studies where deleterious effects of DSA have been demonstrated, and where liver inclusion is protective from HLA class I DSA. This is in line with current national guidelines for immunological risk. Our publicly available research programs could support future large or multicentre studies where statistically relevant data might be gained.

Pharmacogenomic alerts: Developing guidance for use by healthcare professionals.

AIMS: For diseases with a genetic cause, genomics can deliver improved diagnostics and facilitate access to targeted treatments. Drug pharmacodynamics and pharmacokinetics are often dependent on genetic variation underlying these processes. As pharmacogenomics comes of age, it may be the first way in which genomics is utilised at a population level. Still required is guidance and standards of how genomic information can be communicated within the health record, and how clinicians should be alerted to variation impacting the use of medicines. METHODS: The Professional Record Standards Body commissioned by NHS England developed guidance on using pharmacogenomics information in clinical practice. We conducted research with those implementing pharmacogenomics in England and internationally to produce guidance and recommendations for a systems-based approach. RESULTS: A consensus viewpoint is that systems need to be in place to ensure the safe provision of pharmacogenomics information that is curated, actionable and up-to-date. Standards should be established with respect to notification and information exchange, which could impact new or existing prescribing and these must be in keeping with routine practice. Alerting systems should contribute to safer practices. CONCLUSION: Ensuring pharmacogenetics information is available to make safer use of medicines will require a major effort, of which this guidance is a beginning. Standards are required to ensure useful genomic information within the health record can be communicated to clinicians in the right format and at the right times to be actioned successfully. A multidisciplinary group of stakeholders must be engaged in developing pharmacogenomic standards to support the most appropriate prescribing.

Genetically distinct subsets within ANCA-associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS: A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS: We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding α(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P=6.2×10(-89), P=5.6×10(-12,) and P=2.6×10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P=2.1×10(-8)). CONCLUSIONS: This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.).

Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis.

OBJECTIVE: ANCA-associated vasculitis (AAV) is characterized by a chronic relapsing course. Rituximab (RTX) is an effective maintenance treatment; however, the long-term outcomes after its discontinuation are unclear. The aim of this study was to explore the long-term outcomes of AAV patients treated with repeat-dose RTX maintenance therapy. METHODS: AAV patients receiving a RTX treatment protocol consisting of an induction and maintenance phase were included. For initial remission induction, RTX was dosed at 1 g every 2 weeks or 375 mg/m(2) weekly for 4 consecutive weeks and for remission maintenance at 1 g every 6 months for 24 months. At the first RTX administration, ongoing immunosuppressives were withdrawn. RESULTS: Sixty-nine patients were identified, 67 of whom were failing other therapies. Nine relapsed during the RTX treatment protocol; however, all 69 were in remission at the end of the maintenance phase on a median prednisolone dose of 2.5 mg/day and 9% were receiving additional immunosuppression. During subsequent observation, 28 patients relapsed a median of 34.4 months after the last RTX infusion. Risk factors for relapse were PR3-associated disease (P = 0.039), B cell return within 12 months of the last RTX infusion (P = 0.0038) and switch from ANCA negativity to positivity (P = 0.0046). Two patients died and two developed severe hypogammaglobulinaemia. CONCLUSION: This study supports the efficacy and safety of a fixed-interval RTX maintenance regimen in relapsing/refractory AAV. Relapses after discontinuation of maintenance therapy did occur, but at a lower rate than after a single RTX induction course. PR3-associated disease, the switch from ANCA negative to positive and the return of B cells within 12 months of the last RTX administration were risk factors for further relapse.

Impact of donor mismatches at individual HLA-A, -B, -C, -DR, and -DQ loci on the development of HLA-specific antibodies in patients listed for repeat renal transplantation.

We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus-specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus. Two-thirds of patients awaiting repeat transplantation were sensitized (calculated reaction frequency over 15%) and half were highly sensitized (calculated reaction frequency of 85% and greater). Antibody levels peaked after re-listing for repeat transplantation, were independent of graft nephrectomy and were associated with length of time on the waiting list (odds ratio 8.4) and with maintenance on dual immunosuppression (odds ratio 0.2). Sensitization was independently associated with increasing number of donor HLA mismatches (odds ratio 1.4). All mismatched HLA loci contributed to the development of HLA locus-specific antibodies (HLA-A: odds ratio 3.2, HLA-B: odds ratio 3.4, HLA-C: odds ratio 2.5, HLA-DRB1: odds ratio 3.5, HLA-DRB3/4/5: odds ratio 3.9, and HLA-DQ: odds ratio 3.0 (all significant)). Thus, the risk of allosensitization following failure of a first renal transplant increases incrementally with the number of mismatches at all HLA loci assessed. Maintenance of re-listed patients on dual immunosuppression was associated with a reduced risk of sensitization.

The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease.

BACKGROUND: Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. METHODS: We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. RESULTS: Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG <6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG <6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG <3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG <6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG <5 g/L and recurrent infection. CONCLUSIONS: In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. Repeat dose rituximab therapy appears safe with judicious monitoring.

Association of calcium, phosphate and parathyroid hormone with renal allograft function: a retrospective cohort study.

BACKGROUND: Significant variations in postoperative levels of parathyroid hormone (PTH), calcium and phosphate exist after renal transplantation, but whether they affect allograft function is unknown. We investigated the association between early post-transplant levels of PTH, calcium and phosphate and graft function. METHODS: We performed a single-centre cohort study of renal transplant recipients from Addenbrooke's Hospital, Cambridge, between April 1997 and March 2007, evaluating the association between plasma calcium, phosphate and PTH 1 month after transplantation and change in epidermal growth factor receptor (eGFR) in the first 12 months after transplantation (estimated using the Modification of Diet in Renal Disease Study equation). Differences in eGFR between 26 and 52 weeks after transplantation were computed using mixed effects linear regression models for repeated measures of eGFR, while adjusting for sociodemographic and biochemical variables. RESULTS: Three hundred and forty-three patients were eligible for study. The mean age (standard deviation) at transplant was 43 years (13 years). Between 30 and 90 days after transplantation, the median (25th-75th percentile) eGFR was 33 (26-50) ml/min/1.73 m(2), the mean calcium level was 2.4 (0.17) mmol/l and the mean phosphate level was 0.78 (0.23) mmol/l. There was a significant interaction between calcium and phosphate levels (p = 0.006). In patients with low levels of phosphate, higher levels of calcium were associated with declining eGFR over time. However, in patients with a high phosphate level, higher calcium was associated with improved eGFR. CONCLUSIONS: Higher serum calcium in patients with low serum phosphate after transplantation is associated with a decline in graft function during the first year after transplantation. Disorders of mineral metabolism after transplant may represent an important therapeutic target to preserve allograft function.

Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Rituximab is effective induction therapy in refractory or relapsing antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, further relapse is common, and maintenance strategies are required. The aim of this study was to reduce relapse rates using a fixed-interval rituximab re-treatment protocol. METHODS: Retrospective, standardized collection of data from sequential patients receiving rituximab for refractory or relapsing AAV at a single center was studied. Group A patients (n = 28) received rituximab induction therapy (4 infusions of 375 mg/m(2) or 2 infusions 1 gm) and further rituximab at the time of subsequent relapse. Group B patients (n = 45) received routine rituximab re-treatment for 2 years: 2 doses of 1 gm each for remission induction, then 1 gm every 6 months (total of 6 gm). Group C patients (n = 19) comprised patients in group A who subsequently relapsed and began routine re-treatment for 2 years. RESULTS: Response (complete/partial remission) occurred in 26 of the 28 patients (93%) in group A, 43 of the 45 patients (96%) in group B, and 18 of the 19 patients (95%) in group C. At 2 years, relapses had occurred in 19 of 26 patients (73%) in group A, 5 of 43 (12%) in group B (P < 0.001), and 2 of 18 (11%) in group C (P < 0.001). At the last followup (median of 44 months), relapses had occurred in 85% of those in group A (22 of 26), 26% of those in group B (11 of 43; P < 0.001), and 56% of those in group C (10 of 18; P = 0.001). Glucocorticoid dosages were decreased and immunosuppression therapy was withdrawn in the majority of patients. Routine rituximab re-treatment was well tolerated, and no new safety issues were identified. CONCLUSION: Two-year, fixed-interval rituximab re-treatment was associated with a reduction in relapse rates during the re-treatment period and a more prolonged period of remission during subsequent followup. In the absence of biomarkers that accurately predict relapse, routine rituximab re-treatment may be an effective strategy for remission maintenance in patients with refractory and relapsing AAV.

The accuracy of diagnostic coding for acute kidney injury in England - a single centre study.

BACKGROUND: Acute kidney injury (AKI) is an independent risk factor for mortality and is responsible for a significant burden of healthcare expenditure, so accurate measurement of its incidence is important. Administrative coding data has been used for assessing AKI incidence, and shows an increasing proportion of hospital bed days attributable to AKI. However, the accuracy of coding for AKI and changes in coding over time have not been studied in England. METHODS: We studied a random sample of admissions from 2005 and 2010 where ICD-10 code N17 (acute renal failure) was recorded in the administrative coding data at one acute NHS Foundation Trust in England. Using the medical notes and computerised records we examined the demographic and clinical details of these admissions. RESULTS: Against a 6.3% (95% CI 4.8-7.9%) increase in all non-elective admissions, we found a 64% increase in acute renal failure admissions (95% CI 41%-92%, p < 0.001) in 2010 compared to 2005. Median age was 78 years (IQR 72-87), 11-25% had a relevant pre-admission co-morbidity and 64% (55-73%) were taking drugs known to be associated with AKI. Over both years, 95% (91-99%) of cases examined met the Kidney Disease: Improving Global Outcomes criteria for AKI. CONCLUSIONS: Patients with hospital admissions where AKI has been coded are elderly with multiple co-morbidities. Our results demonstrate a high positive predictive value of coding data for a clinical diagnosis of AKI, with no suggestion of marked changes in coding of AKI between 2005 and 2010.

Structured clinical assessment of the ear, nose and throat in patients with granulomatosis with polyangiitis (Wegener's).

The objective of this prospective cross-sectional study is to describe the clinical otorhinolaryngological manifestations of granulomatosis with polyangiitis (Wegener's) (GPA) in a prospective cohort. All patients suffering from GPA seen in a tertiary centre between March 2007 and November 2008 had a detailed clinical assessment by an ENT surgeon of their ear, nose and head and neck complaints. An evaluation of whether there was disease activity and/or infection in each ENT area was made using the European Vasculitis Study Group guidelines. The number of patients assessed was 144. The proportion of female patients was 47 % (n = 69) and the median age was 57.7 years (IQ range 42.5-68.5). The prevalence of ENT involvement was 87 % (125/144). Hearing loss and abnormal tympanic membrane appearance were more common in patients with active disease and no infection (7/8 and 6/8, respectively, in active disease cf. 59/131 and 52/131, respectively, in remission). Nasal crusting was the most common nasal complaint recorded (52/144, 36 %) and bloody rhinorrhoea was the most common symptom in patients with disease activity. Rhinoscopy was highly sensitive in diagnosing disease activity (100 %). Subglottic stenosis was the most common head and neck manifestation (27/121, 22 %) and 74 % were symptomatic. In conclusion, the pattern and frequency of clinical ENT manifestations in GPA have been described in a large patient cohort. The use of tools readily available in the ENT clinic was essential to assess these patients accurately. This dataset will form the basis of an objective scoring system to measure disease activity in the ENT system.

Proof-of-concept solution to create an interoperable timeline of healthcare data.

OBJECTIVES: To overcome the barriers of interoperability by sharing simulated patient data from different electronic health records systems and presenting them in an intuitive timeline of events. METHODS: The 'Patient Story' software comprising database and blockchain, PS Timeline Windows interface, PS Timeline Web interface and network relays on Azure cloud was customised for Epic and Lorenzo electonic patient record (EPR) systems used at different hospitals, using site-specific adapters. RESULTS: Each site could view their own clinical documents and view each other's site specific, fully coded test sets of (Care Connect) medications, conditions and allergies, in an aggregated single view. DISCUSSION: This work has shown that clinical data from different EPR systems can be successfully integrated and visualised on a single timeline, accessible by clinicians and patients. CONCLUSION: The Patient Story system combined the timeline visualisation with successful interoperability across healthcare settings, as well giving patients the ability to directly interact with their timeline.

Using machine learning to model older adult inpatient trajectories from electronic health records data.

Electronic Health Records (EHR) data can provide novel insights into inpatient trajectories. Blood tests and vital signs from de-identified patients' hospital admission episodes (AE) were represented as multivariate time-series (MVTS) to train unsupervised Hidden Markov Models (HMM) and represent each AE day as one of 17 states. All HMM states were clinically interpreted based on their patterns of MVTS variables and relationships with clinical information. Visualization differentiated patients progressing toward stable 'discharge-like' states versus those remaining at risk of inpatient mortality (IM). Chi-square tests confirmed these relationships (two states associated with IM; 12 states with ≥1 diagnosis). Logistic Regression and Random Forest (RF) models trained with MVTS data rather than states had higher prediction performances of IM, but results were comparable (best RF model AUC-ROC: MVTS data = 0.85; HMM states = 0.79). ML models extracted clinically interpretable signals from hospital data. The potential of ML to develop decision-support tools for EHR systems warrants investigation.

Moving from non-emergency bleeps and long-range pagers to a hospital-wide, EHR-integrated secure messaging system: an implementer report.

INTRODUCTION: Obsolete bleep/long-range pager equipment remains firmly embedded in the National Health Service (NHS). OBJECTIVE: To introduce a secure, chart-integrated messaging system (Epic Secure Chat) in a large NHS tertiary referral centre to replace non-emergency bleeps/long-range pagers. METHODS: The system was socialised in the months before go-live. Operational readiness was overseen by an implementation group with stakeholder engagement. Cutover was accompanied by a week of Secure Chat and bleeps running in parallel. RESULTS: Engagement due to socialisation was high with usage stabilising approximately 3 months after go-live. Contact centre internal call activity fell significantly after go-live. No significant patient safety concerns were reported. DISCUSSION: Uptake was excellent with substantial utilisation well before cutover indirectly supporting high levels of engagement. The majority of those who previously carried bleeps were content to use personal devices for messaging because of user convenience after reassurance about privacy. CONCLUSION: An integrated secure messaging system can replace non-emergency bleeps with beneficial impact on service.

Venous thromboembolism with concurrent pulmonary haemorrhage in systemic vasculitis.

BACKGROUND: Pulmonary haemorrhage (PH) is a serious manifestation of systemic vasculitis with high mortality rates yet vasculitis is associated with an increased prevalence of venous thromboembolism (VTE). The concurrent presentation of severe PH and VTE poses a challenge in terms of therapeutic management. METHODS: This is a retrospective case review of the clinical manifestations and response to treatment in vasculitis patients presenting with concurrent pulmonary haemorrhage and VTE (pulmonary embolism and/or deep venous thrombosis). RESULTS: Of 35 patients with severe PH due to systemic vasculitis, 7 (20%) had concurrent VTE. The most common cause was anti-neutrophil cytoplasm antibody-associated vasculitis, followed by anti-glomerular basement membrane disease. Vasculitis responded to conventional therapies and VTE treatment with anticoagulation was uncomplicated in five of six cases. In one case, anticoagulation precipitated the PH and another was not anticoagulated and developed recurrent VTE. All patients survived without further complications after a mean follow-up of 46 months (3-98). CONCLUSIONS: Concurrent VTE occurred in one-fifth of cases with severe PH due to vasculitis. Management of VTE with anticoagulation was effective but led to pulmonary haemorrhage in one patient.

Switching of anti-TNF-α agents in Behçet's disease.

OBJECTIVES: Recent reports suggest efficacy of anti-tumour necrosis factor-alpha (TNF-α) therapy in Behçet's disease. However, the switching of anti-TNF-α agents for treatment failure remains unexplored. Our aims were to describe the efficacy and safety of a second anti-TNF-α agent in Behçet's disease patients after failure of a first agent. METHODS: In this retrospective case series, 34 Behçet's disease patients receiving anti-TNF-α agents, 19 of whom switched to a second anti-TNF-α agent, were identified. We assessed the response to anti-TNF-α agents, the duration of anti-TNF-α therapy, the reasons for withdrawal, adverse events, the Behçet's Disease Current Activity Form (BDCAF), C-reactive protein (CRP), ESR and concomitant therapies at the onset of the first and second anti-TNF-α therapies, and after 6, 12 and 24 months. RESULTS: Clinical improvements were seen in 26/34 (76%) after the first and 18/19 (95%) after the second anti-TNF-α agent. Continuation rates at 24 months were 14.4% after the first and 22.3% after the second anti-TNF-α agent. The most frequent reason for discontinuation was secondary failure in both groups (12 after the first anti-TNF-α agent and 8 after the second). Adverse events leading to treatment withdrawal were seen in 10 after the first anti-TNF-α agent and three after the second. CONCLUSIONS: [corrected] The second anti-TNF-α agent in Behçet's disease demonstrated similar efficacy to that seen with the first agent without new safety concerns, supporting switching to a second anti-TNF-α agent. However, long-term continuation rates for anti-TNF-α therapy were low after both the first and second agents.

Alemtuzumab for refractory primary systemic vasculitis-a randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE).

BACKGROUND: Primary systemic vasculitis (PSV) is a heterogeneous group of autoimmune conditions. There is an unmet need for alternative therapies that lead to sustained remission in patients with refractory disease. Alemtuzumab, an anti-CD52 antibody, depletes lymphocytes for prolonged periods and, in retrospective studies, has induced sustained, treatment-free remissions in patients with refractory/relapsing vasculitis but has raised safety concerns of infection and secondary autoimmunity. This phase IIb clinical trial aimed to assess the efficacy and safety of alemtuzumab, at two different doses, in inducing remission in refractory vasculitis patients. METHODS: The ALEVIATE trial was a randomised, prospective, open-label, dose ranging clinical trial. Patients with refractory ANCA-associated vasculitis (AAV) or Behçet's disease (BD) were randomised to receive either 60 mg or 30 mg alemtuzumab. Treatments were administered at baseline and 6 months or earlier where clinically appropriate. A maximum of three treatments were allowed within the 12-month study period. RESULTS: Twenty-three patients received at least one dose of alemtuzumab. Twelve had AAV, and 11 a diagnosis of BD. The median age was 40 years (range 28-44), with a prior disease duration of 61 months (42-103). Sixteen (70%) achieved either complete (6/23, 26%) or partial (10/23, 44%) response at 6 months. Eight (35%) maintained remission to the end of the trial without relapse. Ten severe adverse events were observed in 7 (30%) patients; 4 were related to alemtuzumab. There were no differences in clinical endpoints between the 60 and 30 mg alemtuzumab treatment groups. CONCLUSION: In a selected group of refractory vasculitis patients, alemtuzumab led to remission in two thirds of patients at 6 months. Remission was maintained to 12 months in a third of the patients, and the safety profile was acceptable. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01405807, EudraCT Number: 2009-017087-17. Registered on April 07, 2011.

A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.

OBJECTIVES: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs). METHODS: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. RESULTS: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms. CONCLUSIONS: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK.

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts. Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient. Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.

UK Renal Registry 13th Annual Report (December 2010): Chapter 14: enhancing access to UK Renal Registry data through innovative online data visualisations.

INTRODUCTION: As the volume of data and analyses grows with time, so does the need to present this increasingly complex information in an accessible and clinically informative manner which is responsive to, and reflects the nature of, the enquiries made by those seeking to access the data. THE UK RENAL REGISTRY INTERACTIVE DATA PORTAL: The UK Renal Registry (UKRR) now has a bespoke interactive data portal which provides a focussed point of access to a variety of graphical display formats and analyses of UKRR data including: · Centre-specific reports--a distillation of annual UKRR data including a colour-coded dashboard summary as well as both funnel plots and longitudinal statistical process control charts for a range of clinical parameters. · Interactive flash-based longitudinal Statistical Process Control charts on a per-centre and per-parameter basis allowing for a more detailed review of performance over time. These charts are the interactive correlates of those available in the centre-specific reports. · Rosling/Gapminder-style motion charts on a perparameter basis simultaneously detailing performance and activity data from multiple centres interactively over time (more details below). · An interactive graphical pivot chart solution using OLAP technology allowing users to design and export their own charts/analyses in real-time using UKRR data. CONCLUSION: This work builds strongly on the wealth of information arising from the high-quality validated UKRR datasets. The portal will empower and engage the UK renal community in the comparative analysis of delivered renal care ultimately leading to enhanced quality improvement over time.

Novel expression signatures identified by transcriptional analysis of separated leucocyte subsets in systemic lupus erythematosus and vasculitis.

OBJECTIVE: To optimise a strategy for identifying gene expression signatures differentiating systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis that provide insight into disease pathogenesis and identify biomarkers. METHODS: 44 vasculitis patients, 13 SLE patients and 25 age and sex-matched controls were enrolled. CD4 and CD8 T cells, B cells, monocytes and neutrophils were isolated from each patient and, together with unseparated peripheral blood mononuclear cells (PBMC), were hybridised to spotted oligonucleotide microarrays. RESULTS: Using expression data obtained from purified cells a substantial number of differentially expressed genes were identified that were not detectable in the analysis of PBMC. Analysis of purified T cells identified a SLE-associated, CD4 T-cell signature consistent with type 1 interferon signalling driving the generation and survival of tissue homing T cells and thereby contributing to disease pathogenesis. Moreover, hierarchical clustering using expression data from purified monocytes provided significantly improved discrimination between the patient groups than that obtained using PBMC data, presumably because the differentially expressed genes reflect genuine differences in processes underlying disease pathogenesis. CONCLUSION: Analysis of leucocyte subsets enabled the identification of gene signatures of both pathogenic relevance and with better disease discrimination than those identified in PBMC. This approach thus provides substantial advantages in the search for diagnostic and prognostic biomarkers in autoimmune disease.