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Objective To contrast the effect of the burden of vasculitis activity with the burden of adverse events on 1-year mortality of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods This study assessed the outcome and adverse events in patients prospectively recruited to four European AAV clinical trials. Data on 524 patients with newly diagnosed AAV were included. The burden of adverse events was quantified using a severity score for leucopenia, infection and other adverse events, with an additional weighting for follow-up duration. A ‘combined burden of events’ (CBOE) score was generated for each patient by summing the individual scores. Vasculitis severity was quantified using the Birmingham vasculitis activity score and glomerular filtration rate (GFR). Results 1-year mortality probability was 11.1%; 59% and 14% of deaths were caused by therapy-associated adverse events and active vasculitis, respectively. Using Cox regression analysis, infection score (p<0.001), adverse event score (p<0.001), leucopenia score (p<0.001) and GFR (p=0.002) were independently associated with mortality. The risk of 1-year mortality remained low (5%) with CBOE scores less than 7, but increased dramatically with scores above this. Hazard ratio for death with a CBOE greater than 7 was 14.4 (95% CI 8.4 to 24.8). Age and GFR were independent predictors of CBOE score. Conclusions The greatest threat to patients with AAV in the first year of therapy is from adverse events rather than active vasculitis. The accumulation of adverse events, monitored using this scoring method, should prompt increased awareness that the patient is at high risk of death.

ObjectiveTo evaluate the effectiveness of reminder letters informed by social normative theory (a type of ‘nudge theory’) on uptake of seasonal influenza vaccination by front-line hospital staff.DesignIndividually randomised controlled trial.SettingA large acute care hospital in England.ParticipantsFront-line staff employed by the hospital (n=7540) were randomly allocated to one of four reminder types in a factorial design.InterventionsThe standard letter included only general information directing the staff to take up the vaccine. A second letter highlighted a type of social norm based on peer comparisons. A third letter highlighted a type of social norm based on an appeal to authority. A fourth letter included a combination of the social norms.Main outcome measureThe proportion of hospital staff vaccinated on-site.ResultsVaccine coverage was 43% (812/1885) in the standard letter group, 43% (818/1885) in the descriptive norms group, 43% (814/1885) in the injunctive norms group and 43% (812/1885) in the combination group. There were no statistically significant effects of either norm or the interaction. The OR for the descriptive norms factor is 1.01 (0.89–1.15) in the absence of the injunctive norms factor and 1.00 (0.88–1.13) in its presence. The OR for the injunctive norms factor is 1.00 (0.88–1.14) in the absence of the descriptive norms factor and 0.99 (0.87–1.12) in its presence.ConclusionsWe find no evidence that the uptake of the seasonal influenza vaccination is affected by reminders using social norms to motivate uptake.

Kidneys from non-white donors have inferior outcomes, but it is unclear if ethnicity matching between donors and recipients achieves better post kidney transplant outcomes. We undertook a retrospective, population cohort study utilising UK Transplant Registry data. The cohort comprised adult, kidney-alone, transplant recipients receiving their first kidney transplant between 2003-2015, with data censored at 1st October 2016. We included 27,970 recipients stratified into white (n = 23,215), black (n = 1,679) and south Asian (n = 3,076) ethnicity, with median post-transplant follow-up of 1,676 days (IQR 716-2,869 days). Unadjusted and adjusted Cox regression survival analyses were performed to investigate ethnicity effect on risk for graft loss and mortality. In unadjusted analyses, matched ethnicity between donors-recipients resulted in better outcomes for delayed graft function, one-year creatinine, graft and patient survival but these differed by ethnicity matches. Compared to white-to-white transplants, risk for death-censored graft loss was higher in black-to-black and similar among Asian-to-Asian transplants, but mortality risk was lower for both black-to-black and Asian-to-Asian transplants. In Cox regression models, compared to white donors, we observed higher risk for graft loss with both south Asian (HR 1.38, 95%CI 1.12-1.70, p = 0.003) and black (HR 1.66, 95%CI 1.30-2.11, p<0.001) donated kidneys independent of recipient ethnicity. We observed no mortality difference with south Asian donated kidneys but increased mortality with black donated kidneys (HR 1.68, 95%CI 1.21-2.35, p = 0.002). Matching ethnicities made no significant difference in any Cox regression model. Similar results were observed after stratifying our analysis by living and deceased-donor kidney transplantation. Our data confirm inferior outcomes associated with non-white kidney donors for kidney transplant recipients of any ethnicity in a risk-adjusted model for the United Kingdom population. However, contrary to non-renal transplant literature, we did not identify any survival benefits associated with donor-recipient ethnicity matching.

ObjectivesThe Fontan procedure provides palliation for patients with complex congenital heart disease. A late complication is the development of a pro-arrhythmogenic environment. Modifications to the surgical technique try and reduce the incidence of late arrhythmia. This study aims to establish incidence and outcome of arrhythmias in Fontan patients with long-term follow-up.MethodsRetrospective analysis of adult patients with a Fontan circulation cared for by University Hospitals Birmingham between 2001 and 2013.Results166 patients, mean age 29.1 years, were identified (63% atriopulmonary (AP) Fontan, 13% lateral tunnel (LT), 24% extracardiac total cavopulmonary connection (TCPC)). The mean follow-up since Fontan surgery was 18.6 years. 42% (70 patients) had suffered at least one tachyarrhythmia, with 100% incidence of arrhythmia in AP Fontan patients surviving at least 26 years following surgery. The most common arrhythmia was intra-atrial re-entrant tachycardia (66%). There was also a significant incidence of arrhythmia in the LT and TCPC groups (23% at mean follow-up of 19.6 years and 13.6 years, respectively). 44 patients had undergone electrical cardioversion, 30 had ablations and 10 had undergone Fontan conversion surgery. Survival analysis showed only age at the time of Fontan as a significant predictor for arrhythmia onset (p<0.001) irrespective of surgical approach.ConclusionsThere is a significant, increasing arrhythmia burden in adult patients with a Fontan circulation. Arrhythmia development could be regarded as an inevitable consequence of an AP Fontan. There remains a high incidence of arrhythmia with more modern surgical approaches. The long-term future of these patients is unclear and their care poses significant challenges.

Recent literature in mechanical ventilation includes strong evidence from randomized trials. Little information is available regarding the influence of these trials on usual clinical practice. To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort. A prospective international observational cohort study, with a nested comparative study performed in 349 intensive care units in 23 countries. We enrolled 4,968 consecutive patients receiving mechanical ventilation over a 1-month period. We recorded demographics and daily data related to mechanical ventilation for the duration of ventilation. We systematically reviewed the literature and developed 11 practice-change hypotheses for the comparative cohort study before seeing these results. In assessing practice changes, we only compared data from the 107 intensive care units (1,675 patients) that also participated in the 1998 cohort (1,383 patients). In 2004 compared with 1998, the use of noninvasive ventilation increased (11.1 vs. 4.4%, P < 0.001). Among patients with acute respiratory distress syndrome, tidal volumes decreased (7.4 vs. 9.1 ml/kg, P < 0.001) and positive end-expiratory pressure levels increased slightly (8.7 vs. 7.7 cm H(2)O, P = 0.02). More patients were successfully extubated after their first attempt of spontaneous breathing (77 vs. 62%, P < 0.001). Use of synchronized intermittent mandatory ventilation fell dramatically (1.6 vs. 11%, P < 0.001). Observations confirmed 10 of our 11 practice-change hypotheses. The strong concordance of predicted and observed practice changes suggests that randomized trial results have advanced mechanical ventilation practices internationally.

Introduction Trials of tight glucose control have compared measures of central tendency, such as average blood glucose, and yielded conflicting results. Other metrics, such as standard deviation, reflect different properties of glucose control and are also associated with changes in outcome. It is possible, therefore, that the conflicting results from interventional studies arise from effects on glycaemic control that have not been reported. Methods Using glucose measurements from patients admitted to four adult intensive care units in one UK hospital, we sought to identify metrics of glycaemic control, examine the relationship between them and identify the metrics that are both independently and most strongly associated with outcome. Results We examined nine previously described metrics and identified a further four. Cluster analysis classified these metrics into two families, namely, those reflecting measures of central tendency and those reflecting measures of dispersion. A measure of minimum glucose was also identified but related to neither family. Plots of the quintiles of these metrics against hospital mortality revealed population-specific relationships. Areas under receiver-operating characteristic curves could not identify an optimum metric of central tendency or dispersion. Using odds ratios, we were able to show that the effect of these metrics is independent of one another. Conclusion Our results suggest that glycaemic control is associated with outcome on the basis of three independent metrics, reflecting measures of central tendency, measures of dispersion and a measure of minimum glucose.

Background There is a need for a large, contemporary, multi-centre series of measured glomerular filtration rates (mGFR) from healthy individuals to determine age- and gender-specific reference ranges for GFR. We aimed to address this and to use the ranges to provide age- and gender-specific advisory GFR thresholds considered acceptable for living kidney donation. Methods Individual-level data including pre-donation mGFR from 2974 prospective living kidney donors from 18 UK renal centres performed between 2003 and 2015 were amalgamated. Age- and gender-specific GFR reference ranges were determined by segmented multiple linear regression and presented as means ± two standard deviations. Results Males had a higher GFR than females (92.0 vs 88.1 mL/min/1.73m 2 , P  < 0.0001). Mean mGFR was 100 mL/min/1.73m 2 until 35 years of age, following which there was a linear decline that was faster in females compared to males (7.7 vs 6.6 mL/min/1.73m 2 /decade, P  = 0.013); 10.5% of individuals aged > 60 years had a GFR < 60 mL/min/1.73m 2 . The GFR ranges were used along with other published evidence to provide advisory age- and gender-specific GFR thresholds for living kidney donation. Conclusions These data suggest that GFR declines after 35 years of age, and the decline is faster in females. A significant proportion of the healthy population over 60 years of age have a GFR < 60 mL/min/1.73m 2 which may have implications for the definition of chronic kidney disease. Age and gender differences in normal GFR can be used to determine advisory GFR thresholds for living kidney donation.

Background Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. Methods We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 μmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. Results Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4–5.3], p  = 0.004) and higher incidence of diabetes (HR 6.33 [1.94–20.63], p  = 0.002), after adjustment for confounding factors. Conclusions The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes.

ObjectiveSusceptibility of patients with cancer to COVID-19 pneumonitis has been variable. We aim to quantify the risk of hospitalisation in patients with active cancer and use a machine learning algorithm (MLA) and traditional statistics to predict clinical outcomes and mortality.DesignRetrospective cohort study.SettingA single UK district general hospital.ParticipantsData on total hospital admissions between March 2018 and June 2020, all active cancer diagnoses between March 2019 and June 2020 and clinical parameters of COVID-19-positive admissions between March 2020 and June 2020 were collected. 526 COVID-19 admissions without an active cancer diagnosis were compared with 87 COVID-19 admissions with an active cancer diagnosis.Primary and secondary outcome measures30-day and 90-day post-COVID-19 survival.ResultsIn total, 613 patients were enrolled with male to female ratio of 1:6 and median age of 77 years. The estimated infection rate of COVID-19 was 87 of 22 729 (0.4%) in the patients with cancer and 526 of 404 379 (0.1%) in the population without cancer (OR of being hospitalised with COVID-19 if having cancer is 2.942671 (95% CI: 2.344522 to 3.693425); p<0.001). Survival was reduced in patients with cancer with COVID-19 at 90 days. R-Studio software determined the association between cancer status, COVID-19 and 90-day survival against variables using MLA. Multivariate analysis showed increases in age (OR 1.039 (95% CI: 1.020 to 1.057), p<0.001), urea (OR 1.005 (95% CI: 1.002 to 1.007), p<0.001) and C reactive protein (CRP) (OR 1.065 (95% CI: 1.016 to 1.116), p<0.008) are associated with greater 30-day and 90-day mortality. The MLA model examined the contribution of predictive variables for 90-day survival (area under the curve: 0.749); with transplant patients, age, male gender and diabetes mellitus being predictors of greater mortality.ConclusionsActive cancer diagnosis has a threefold increase in risk of hospitalisation with COVID-19. Increased age, urea and CRP predict mortality in patients with cancer. MLA complements traditional statistical analysis in identifying prognostic variables for outcomes of COVID-19 infection in patients with cancer. This study provides proof of concept for MLA in risk prediction for COVID-19 in patients with cancer and should inform a redesign of cancer services to ensure safe delivery of cancer care.

BackgroundStudies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients.MethodsPatients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching.ResultsAll patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6).ConclusionsThose of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.