Demographics, distribution and experiences of UK clinical academic trainees using GMC NTS Survey data.

Involvement in research plays an integral role in the delivery of high-quality patient care, benefitting doctors, patients and employers. It is important that access to clinical academic training opportunities are inclusive and equitable. To better understand the academic trainee population, distribution of academic posts and their reported experience of clinical training, we analysed 53 477 anonymous responses from General Medical Council databases and the 2019 National Training Survey. Academic trainees are more likely to be men, and the gender divide begins prior to graduation. There are very low numbers of international medical graduates and less than full-time academic trainees. A small number of UK universities produce a greater prevalence of doctors successfully appointed to academic posts; subsequent academic training also clusters around these institutions. At more senior levels, academic trainees are significantly more likely to be of white ethnicity, although among UK graduates, no ethnicity differences were seen. Foundation academic trainees report a poorer experience of some aspects of their clinical training placements, with high workloads reported by all academic trainees. Our work highlights important disparities in the demographics of the UK clinical academic trainee population and raises concerns that certain groups of doctors face barriers accessing and progressing in UK academic training pathways.

Demographics, distribution and experiences of UK clinical academic trainees using GMC NTS Survey data.

Involvement in research plays an integral role in the delivery of high-quality patient care, benefitting doctors, patients and employers. It is important that access to clinical academic training opportunities are inclusive and equitable. To better understand the academic trainee population, distribution of academic posts and their reported experience of clinical training, we analysed 53 477 anonymous responses from General Medical Council databases and the 2019 National Training Survey. Academic trainees are more likely to be men, and the gender divide begins prior to graduation. There are very low numbers of international medical graduates and less than full-time academic trainees. A small number of UK universities produce a greater prevalence of doctors successfully appointed to academic posts; subsequent academic training also clusters around these institutions. At more senior levels, academic trainees are significantly more likely to be of white ethnicity, although among UK graduates, no ethnicity differences were seen. Foundation academic trainees report a poorer experience of some aspects of their clinical training placements, with high workloads reported by all academic trainees. Our work highlights important disparities in the demographics of the UK clinical academic trainee population and raises concerns that certain groups of doctors face barriers accessing and progressing in UK academic training pathways.

Shared alloimmune responses against blood and transplant donors result in adverse clinical outcomes following blood transfusion post-renal transplantation.

De novo HLA donor-specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyze the development of HLA transfusion-specific antibodies (TSA) to blood donors of transfusions given posttransplant and examine the impact on clinical outcomes. A total of 244 blood donors of transfusions received by 86 transplant patients (46 who developed a DSA post transfusion and 40 who remained DSA negative) were HLA typed. De novo TSA developed against 150/244 (61.5%) blood donors. In 70/150 (46.7%) cases the TSA was of shared HLA antibody specificity with a DSA response in the recipient (DSA+ = TSA+). This occurred when there was a greater overall HLA match between the blood and transplant donor. DSA+ = TSA+ patients had increased risk of allograft failure (P = .0025) and AMR (P = .02) compared with the DSA+ ≠ TSA+ patients. To conclude, PTBT may elicit de novo HLA antibodies. Enhanced HLA matching between the blood and transplant donor is more likely to result in a DSA and TSA of shared antibody specificities. Transfusion avoidance or the use of HLA matched or selected blood may reduce this risk and improve outcomes.

Circulating complement factor H-related proteins 1 and 5 correlate with disease activity in IgA nephropathy.

IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation. From a large cohort of patients, we demonstrated that plasma FHR-1 and the FHR-1/fH ratio were elevated in IgAN and associated with progressive disease. Plasma FHR-1 negatively correlated with eGFR but remained elevated in patients with IgAN with normal eGFR. Serum FHR5 was slightly elevated in IgAN but did not correlate with eGFR. Neither FHR5 levels nor the FHR-5/fH ratio was associated with progressive disease. However, higher serum FHR-5 levels were associated with a lack of response to immunosuppression, the presence of endocapillary hypercellularity, and histology scores of disease severity (the Oxford Classification MEST score). Thus, FHR-1 and FHR-5 have a role in IgAN disease progression.

Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment.

Background: Endocapillary hypercellularity independently predicts renal outcome in immunoglobulin A nephropathy (IgAN). Mycophenolate mofetil (MMF) treatment is offered to patients presenting to the Imperial College Renal and Transplant Centre with IgAN and histological evidence of endocapillary hypercellularity. Clinical trials of MMF in IgAN have been inconclusive and have been limited by a lack of specific histological inclusion and exclusion criteria when recruiting patients. Evidence of histological improvement following MMF treatment would support its therapeutic use. We therefore reviewed histological changes after MMF therapy in a cohort of IgAN patients. Method: Eighteen IgAN patients with native renal biopsies before and after repeated MMF treatment were identified. Patients were excluded if they had received any other immunosuppressive therapy, including corticosteroids. On the basis of the Oxford Classification of IgAN, we reviewed histological changes after MMF treatment. Results: Nine patients (50%) were male. At diagnostic renal biopsy, the median age was 35 years [interquartile range (IQR) 30-41], serum creatinine was 97 µmol/L (IQR 79-153) and urine protein creatinine ratio (UPCR) was 146 mg/mmol (IQR 98-212). The median time between biopsies was 24 months (range 9-41). Following MMF treatment, repeat biopsy demonstrated statistically significant improvement in the mean percentage of glomeruli showing endocapillary hypercellularity and cellular/fibrocellular crescents. There was no change in mesangial hypercellularity, segmental sclerosis or tubular atrophy scores. Mesangial IgA deposition was also significantly reduced. Histopathological improvement persisted after the cessation of MMF therapy, suggesting that 2 years of treatment is adequate for benefit. The median serum creatinine remained stable at 3 years follow-up at 104 µmol/L (IQR 79-147). Conclusion: MMF treatment is associated with histopathological improvement in IgAN.

Rituximab in systemic lupus erythematosus and lupus nephritis.

Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN ­ one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN ­ it is a biologically plausible agent with a huge amount of supportive anecdotal clinical data. Yet the completed trials have been negative to date despite clinical experience strongly suggesting efficacy. It is hoped that the two new trials will determine the role for rituximab, at least in LN.

Delivering Person-Centered Peritoneal Dialysis.

Peritoneal dialysis (PD) enables people to have a home-based therapy, permitting greater autonomy for individuals along with enhanced treatment satisfaction compared with in-center dialysis care. The burden of treatment on PD, however, remains considerable and underpins the need for person-centered care. This reflects the need to address the patient as a person with needs and preferences beyond just the medical perspective. Shared decision making is central to the recent International Society for Peritoneal Dialysis recommendations for prescribing PD, balancing the potential benefits of PD on patient well-being with the burden associated with treatment. This review considers the role of high-quality goal-directed prescribing, incremental dialysis, and remote patient monitoring in reducing the burden of dialysis, including an approach to implementing incremental PD. Although patient-related outcomes are important in assessing the response to treatment and, particularly life participation, the corollary of dialysis burden, there are no clear routes to the clinical implementation of patient-related outcome measures. Delivering person-centered care is dependent on treating people both as individuals and as equal partners in their care.

Perceived Life Expectancy Among Dialysis Recipients: A Scoping Review.

Rationale & Objective: Greater prognostic understanding is associated with higher quality care at the end of life. We undertook a scoping review to explore how long dialysis recipients expect to live. Study Design: Scoping Review. Setting & Study Populations: People with kidney failure over 18 years old. Search Strategy & Sources: Studies were identified by searching Medline, Embase, APA PsycINFO, HMIC, and ProQuest database for terms related to "life expectancy", "self-estimated", and "end stage kidney disease". Data Extraction: Search strategies reported 349 unique, potentially eligible studies, with 8 studies meeting the inclusion criteria after screening. Results: Significant mismatches between dialysis recipients and their health care provider's estimations of prognosis were reported, with patients predicting significantly higher life expectancies than health care professionals and almost no agreement between patient and nephrologist's estimates of 1-year survival. Documented cognitive impairment did not affect 1-year or 5-year prognosis estimates, nor did gender, age, time on dialysis, or discussing perceived life expectancy. Dialysis recipients who thought they were on the transplant list or who self-identified as African American reported higher perceived life expectancy, whereas people who were 75 years or older, or with fair or poor self-reported health status reported a lower perceived life expectancy. Those with a lower perceived life expectancy preferred care focusing on relieving pain and discomfort, whereas people who thought they had a higher chance of survival were significantly more likely to prefer life-extending care. Limitations: There is a marked paucity of research in this area, with most studies conducted in North American cohorts. Conclusions: Optimistic patient prognostic expectations persist in dialysis recipients. Given the effects of perceived life expectancy on treatment choices and subsequent quality of life, it is important that transparent discussions regarding prognosis are conducted with people receiving dialysis and their families. Plain-Language Summary: Understanding illness severity and prognosis allows people to make decisions and prioritize areas of their lives that are important to them. We undertook a scoping review to explore how long dialysis recipients expect to live. We found significant mismatches between the perceived life expectancy of people treated with dialysis and their health care providers. Perceived life expectancy influenced treatment choices; thus, those who thought they would die sooner prioritized care focusing on relieving pain and discomfort. Those who thought they had a higher chance of survival were more likely to prefer life-extending care (with potential effects on quality of life). It is important to have frank discussions about prognosis with people receiving dialysis, to empower individuals and help them make informed decisions about their care.

Sex and Gender in Glomerular Disease.

There is increasing understanding that a multifaceted interplay of sex-dependent genetic and immune dysregulation underpins the development of glomerular disorders. Regional and ethnic variations in glomerular disease incidence make delineating the effects of sex and gender on disease pathophysiology more complex, but there is a marked paucity of research in this area. This review article presents a summary of the current understanding of sex and gender in glomerular disease, highlighting the broader effects of sex and gender on autoimmunity, clinical presentations, and pathophysiology of individual glomerular diseases, as well as exploring sex, gender, and glomerular disease within a wider socioenvironmental context. It is important to specifically consider the effects of sex and gender when presenting and analyzing clinical and scientific studies on glomerular disease. Failure to do so risks promoting disparities within health care provision, neglecting opportunities to identify sex-specific biomarkers, and potentially hindering the development of sex-specific therapies.

Burnout and long COVID among the UK nephrology workforce: results from a national survey investigating the impact of COVID-19 on working lives.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is placing a significant strain on healthcare. We conducted a national survey of the UK nephrology workforce to understand its impacts on their working lives. METHODS: An online questionnaire incorporating the Maslach Burnout Inventory score was distributed between 31 March and 1 May 2021, with a focus on COVID-19 and long COVID incidence, vaccine uptake, burnout and working patterns. Data were analysed qualitatively and quantitatively; multivariable logistic regression was used to identify associations. RESULTS: A total of 423 responses were received. Of them, 29% had contracted COVID-19, which was more common among doctors and nurses {odds ratio [OR] 2.18 [95% confidence interval (CI) 1.13-4.22]} and those <55 years of age [OR 2.60 (95% CI 1.38-4.90)]. Of those who contracted COVID-19, 36% had symptoms of long COVID, which was more common among ethnicities other than White British [OR 2.57 (95% CI 1.09-6.05)]. A total of 57% had evidence of burnout, which was more common among younger respondents [OR 1.92 (95% CI 1.10-3.35)] and those with long COVID [OR 10.31 (95% CI 1.32-80.70)], and 59% with reconfigured job plans continued to work more hours. More of those working full-time wished to retire early. A total of 59% experienced remote working, with a majority preference for continuing this in the future. In terms of vaccination, 95% had received one dose of a COVID-19 vaccine and 86% had received two doses by May 2021. CONCLUSIONS: Burnout and long COVID is prevalent with impacts on working lives. Some groups are more at risk. Vaccination uptake is high and remote and flexible working were well received. Institutional interventions are needed to prevent workforce attrition.

Research engagement by British early-career practitioners in nephrology: a multidisciplinary survey.

OBJECTIVES: To establish barriers and motivators underlying research engagement among early-career practitioners in nephrology across the UK, in order to guide potential interventions to enhance research involvement in renal units. DESIGN: Cross-sectional online survey employing a range of free-text, Likert scale and binomial/multiple-choice responses, distributed via mailing lists and social media. Topics covered research experience, research involvement and barriers, impact of COVID-19 and strategies to improve research engagement. Thematic analysis was used to assess free-text responses. SETTING: Renal units throughout the UK. PARTICIPANTS: Non-consultant healthcare staff self-identifying as working in nephrology were included (n=211), with responses from non-UK respondents or consultant nephrologists excluded (n=12). RESULTS: Responses were received from across the multidisciplinary team (physicians (n=83) and nurses (n=83)) and other allied health professionals (n=45). Most were aware of ongoing local research, but under half of them were actively involved. Multivariate analysis indicated employment as a physician, protected time for research activity and provision of appropriate training were associated with greater research experience and output. There was general enthusiasm to undertake research, but perceived barriers included insufficient staffing, lack of time, funding and encouragement. COVID-19 was felt to have further impacted negatively upon opportunities. Among the suggested strategies to promote engagement, mentorship and an online research resource were felt to be of most interest. CONCLUSIONS: In the first survey of this type in nephrology, we demonstrate differences across the multidisciplinary spectrum in perceived research experience and accessibility, which have been worsened by COVID-19. Our findings will guide strategies to broaden engagement in early-career practitioners and serve as a baseline to assess the impact of these interventions.

Gender Differences in Experiences and Expectations of Hemodialysis in a Frail and Seriously Unwell Patient Population.

Introduction: Surprisingly few studies have explored the experiences of seriously unwell people with kidney disease on hemodialysis therapy: we conducted a mixed-methods study to investigate gender differences in illness experience, symptom burden, treatment considerations or expectations in this cohort. Methods: Seriously unwell people on hemodialysis (1-year mortality risk of >20%) at 3 hospital-based units were invited to take part in a structured interview or to complete the same questions independently via a questionnaire. A total of 54 people took part (36 males, 18 females); data analysis was undertaken using a thematic approach. Results: "Desire to keep living" is the most important and basic thought process when starting dialysis. Fear also predominates influencing risk assessment and decision-making. Once fear is managed, there are physical, social, practical and emotional issues to rationalize, but choice only seems possible if shared decision-making is part of the consultation.Gender differences were seen in perceived hopes and expectations of treatment. Males were more likely to prioritize achievement of physical goals, with females prioritizing a wish to feel well. Both genders reported significantly higher symptom scores than their health care provider perceived, however this difference was more marked in females. Dialysis regret existed in >50% of participants and 6 out of 54 (11%) stated that they would have chosen no dialysis at all. Females were more likely to report feeling depressed (P = 0.001). Conclusion: Different genders approach treatment decisions and prioritize treatment expectations differently. Recognizing this will allow personalized care plans to be developed and improve the experiences of seriously unwell people with kidney disease.

Impact of changing medical workforce demographics in renal medicine over 7 years: Analysis of GMC national trainee survey data.

Increasing numbers of doctors in training are taking career breaks, with burnout cited as a potential cause. This study analysed General Medical Council (GMC) national training survey data (renal medicine) to understand the impacts of changing workforce demographics on trainee outcomes and wellbeing. Increasing proportions of female, Black, Asian and minority ethnic (BAME), and international medical graduates are entering the workforce. Specialty exam pass rates have fallen and are lower for BAME and international medical graduates in renal medicine. Time to complete higher specialty training has increased for female trainees. Self-reported burnout rates for renal trainees were higher than other medical specialties and highest for male BAME trainees. Burnout was only partially mitigated by less-than-full-time working, but had no impact on progression, sick-leave or time out of training. It is important to recognise changes to the workforce and proactively plan to effectively support a more diverse group of trainees, to enable them to succeed and reduce differential attainment.

Perceptions of Illness Severity, Treatment Goals, and Life Expectancy: The ePISTLE Study.

INTRODUCTION: A better understanding of factors influencing perceived life expectancy (PLE), interactions between patient prognostic beliefs, experiences of illness, and treatment behavior is urgently needed. METHODS: Case-notes at 3 hemodialysis units were screened: patients with ≥20% 1-year mortality risk were included. Patients and their health care professionals (HCPs) were invited to complete a structured interview or mixed-methods questionnaire. Four hundred eleven patient notes were screened. Seventy-seven eligible patients were approached and 51 were included. RESULTS: Patients predicted significantly higher life expectancies than HCPs (P < 0.0001). Documented cognitive impairment, gender, or increasing age did not affect 1- or 5-year PLE. PLE influenced priorities of care: one-fifth of patients who estimated themselves to have >95% 1-year survival preferred "care focusing on relieving pain and discomfort," compared with nearly three-quarters of those reporting a ≤50% chance of 1-year survival. Twenty of 51 (39%) patients believed transplantation was an option for them, despite only 4 being waitlisted at the time of the interview. Patients who thought they were transplant candidates were significantly more confident they would be alive at 1 and 5 years and to want resuscitation attempted. Cognitive impairment had no effect on perceived transplant candidacy. A high symptom burden was present and underrecognized by HCPs. High symptom burden was associated with significantly lower PLE at both 1 and 5 years, increased anxiety/depression scores, and treatment choices more likely to prioritize relief of suffering. CONCLUSION: There is a disparity between patient PLE and those of their HCPs. Severity of symptom burden and beliefs regarding PLE or transplant candidacy affect patient treatment preferences.

Resuming Deceased Donor Kidney Transplantation in the COVID-19 Era: What Do Patients Want?

BACKGROUND: The rapidly evolving novel coronavirus 2019 (COVID-19) pandemic bought many kidney transplant (KT) programs to a halt. Integral to resuming KT activity is understanding the perspectives of potential transplant candidates during this highly dynamic time. METHODS: From June 1 to July 7, 2020, a telephone survey of KT candidates on the deceased donor waiting list at Imperial College Renal and Transplant Centre in West London was conducted. The survey captured ongoing COVID-19 exposure risks and patients' views on waitlist (WL) reactivation and undergoing transplantation. RESULTS: Two hundred seven responses were received. Of the respondents, 180 patients (87%) were happy to be reactivated onto the WL; with 141 patients (68%) willing to give consent to transplantation currently, while 53 patients (26%) felt unsure, and 13 patients (6%) would decline a KT. The vast majority of patients had no concerns. In the responses from those who were uncertain or who would decline a KT, concerns about COVID-19 infection and the need for reassurance from transplant units dominated. Universally patients wanted more information about COVID-19 infection risk with KT and the precautions being taken to reduce this risk. CONCLUSIONS: The majority of surveyed patients are in favor of reactivation and receiving a KT despite the ongoing COVID-19 pandemic. Reactivation of candidates cannot be assumed and should take an individualized approach, incorporating clinical risk with patient perspectives. Improved communication with KT candidates is highly requested.

A review of blood product usage in a large emergency department over a one-year period.

OBJECTIVES: To establish blood product usage and wastage within a UK emergency department (ED). METHODS: A retrospective case note review of patients presenting to the ED requiring blood products. RESULTS: Between 1 January 2007 and 31 December 2007, 770 transfusion requests were identified, representing 3209 units of blood products. Gastrointestinal bleeding was the most frequent indication for blood product request. 39.5% (1204 units) of blood products ordered were transfused, 47.8% (1458 units) recycled (including 53.4%; 1260 units; of red cell concentrate; RCC), 3.2% (97 units) wasted and 9.5% (289 units) unaccounted for. Median age of recipients was 65 (IQR 46-78) years and 56% of all transfusions were given to patients over 60 years old. CONCLUSION: Patients receiving blood products are elderly. Up to half of all requested products are recycled having not being used for the indication for which they were requested, and 3% of blood products are wasted. With an ageing population and limited blood product availability, transfusion requests should be more carefully considered.

Food, microbes, sex and old age: on the plasticity of gastrointestinal innervation.

The gastrointestinal tract is innervated by its own enteric nervous system and by extrinsic neurons that connect it with the central nervous system. Innervation allows the gastrointestinal tract to sense and respond to diverse stimuli, adjusting motility and secretion, but also affecting our physiology, behaviour and immunity. The mechanisms underlying the formation of gastrointestinal neurons are beginning to be elucidated; those that keep them plastic over an organism's lifetime remain to be explored. Here, we review the effects of microbiota, nutrients, sex and ageing on the morphology and function of gastrointestinal innervation in mammals, and discuss how this plasticity shapes gut-brain crosstalk and whole-body physiology. We also highlight insights gained by nascent studies of the enteric innervation of Drosophila melanogaster.