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

BackgroundThe 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.MethodsAn 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.ResultsA 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 ConclusionsBurnout 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

Distinct Neutralising and Complement-Fixing Antibody Responses Can Be Induced to the Same Antigen in Haemodialysis Patients After Immunisation with Different Vaccine Platforms

Background/Objectives: Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Vaccine-induced immunity is typically reduced in HD populations. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen-Spike (S)-glycoprotein-after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Methods: We compared the total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. Results: After 2 doses of the same vaccine, HD patients had anti-S antibody levels and a complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV (defined by the presence of both complement binding and cross-variant neutralisation activity). Interestingly, an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients without a prior history of SARS-CoV-2 infection. Conclusions: HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population. </p

Acoustic trauma slows AMPAR-mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function

Damaging levels of sound (acoustic trauma, AT) diminish peripheral synapses, but what is the impact on the central auditory pathway? Developmental maturation of synaptic function and hearing were characterized in the mouse lateral superior olive (LSO) from postnatal day 7 (P7) to P96 using voltage-clamp and auditory brainstem responses. IPSCs and EPSCs show rapid acceleration during development, so that decay kinetics converge to similar sub-millisecond time-constants (τ, 0.87 ± 0.11 and 0.77 ± 0.08 ms, respectively) in adult mice. This correlated with LSO mRNA levels for glycinergic and glutamatergic ionotropic receptor subunits, confirming a switch from Glyα2 to Glyα1 for IPSCs and increased expression of GluA3 and GluA4 subunits for EPSCs. The NMDA receptor (NMDAR)-EPSC decay τ accelerated from >40 ms in prehearing animals to 2.6 ± 0.4 ms in adults, as GluN2C expression increased. In vivo induction of AT at around P20 disrupted IPSC and EPSC integration in the LSO, so that 1 week later the AMPA receptor (AMPAR)-EPSC decay was slowed and mRNA for GluA1 increased while GluA4 decreased. In contrast, GlyR IPSC and NMDAR-EPSC decay times were unchanged. Computational modelling confirmed that matched IPSC and EPSC kinetics are required to generate mature interaural level difference functions, and that longer-lasting EPSCs compensate to maintain binaural function with raised auditory thresholds after AT. We conclude that LSO excitatory and inhibitory synaptic drive matures to identical time-courses, that AT changes synaptic AMPARs by expression of subunits with slow kinetics (which recover over 2 months) and that loud sounds reversibly modify excitatory synapses in the brain, changing synaptic function for several weeks after exposure

Primary IgA nephropathy: new insights and emerging therapies

Primary IgA nephropathy (IgAN) is a common glomerular disorder defined by predominant mesangial IgA deposition. Once thought to follow a progressive course in 10-20% of those diagnosed, emerging evidence now suggests most will progress to kidney failure over their lifetimes. Although the lack of safe and effective treatments to impede disease progression continues to present a challenge, the landscape of IgAN has dramatically evolved over the last 2 years. Driven by fundamental changes to accepted end points for IgAN clinical trials as well as fascinating new insights into the pathophysiology of IgAN, a swathe of novel and repurposed therapies are currently being evaluated. Already, two novel drugs, targeted-release formulation budesonide and sparsentan, have received conditional approvals for the treatment of IgAN, with sodium glucose co-transporter 2 inhibitors establishing themselves as further options. Soon to join this ensemble are likely to be treatments that modulate the complement system and B-cell activity; several are currently undergoing clinical trials in IgAN with promising interim results. In this review, we provide an overview of evolving epidemiological insights, disease mechanisms, emerging therapies, and contemporary challenges surrounding the management of IgAN.https://www.sciencedirect.com/science/article/abs/pii/S2949813924000727?via%3Dihu

Can artificial intelligence predict the need for acute renal replacement therapy among inpatients with acute kidney injury?

https://www.rcpjournals.org/content/futurehosp/10/Suppl_3/1

Regional variations in nephrology trainee confidence with clinical skills may relate to the availability of local training opportunities in the UK: results from a national survey

Background: The United Kingdom offers a standardised training program for nephrology fellows. However, local training opportunities vary resulting in mismatches between trainee interests and accessible opportunities. This may impact trainee confidence, satisfaction, and future service provision. Methods: A survey assessing confidence with key procedures and sub-specialities was disseminated. Associations with region of training were probed using Chi square tests, with significance set at p < 0.0008 following a Bonferroni correction. Results were compared to trainee views on available opportunities for development. Results: 139 responses were received (32% response rate, demographics representative of the UK nephrology trainee cohort). Procedural independence varied from 98% for temporary femoral vascular catheters to 5% for peritoneal dialysis catheters (PDIs). Independence with inserting tunnelled vascular catheters varied with region (p < 0.0001). Trainees expressed a desire for formal training in kidney ultrasound scanning and PDIs, corresponding with procedures they had least opportunity to become independent with. Trainees felt least confident managing kidney disease in pregnancy. Suggestions for improving training included protected time for garnering sub-speciality knowledge, developing procedural skills and for experiencing practice in other nephrology units. Conclusions: A mismatch between trainee interests and professional development opportunities exists, which may threaten trainee autonomy and impact patient care particularly with regards to peritoneal dialysis. Provisions to facilitate trainee directed development need to be made while balancing the rigors of service provision. Such measures could prove critical to promoting trainee well-being and preventing attrition within the nephrology workforce.https://link.springer.com/article/10.1007/s10157-022-02228-

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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754810

Technological innovations to improve patient engagement in nephrology

Technological innovation has accelerated exponentially over the last 2 decades. From the rise of smartphones and social media in the early 2000s to the mainstream accessibility of artificial intelligence (AI) in 2023, digital advancements have transformed the way we live and work. These innovations have permeated health care, covering a spectrum of applications from virtual reality training platforms to AI-powered clinical decision support tools. In this review, we explore fascinating recent innovations that have and can facilitate patient engagement in nephrology. These include integrated care mobile applications, wearable health monitoring tools, virtual/augmented reality consultation and education platforms, AI-powered appointment booking systems, and patient information tools. We also discuss potential pitfalls in implementation and paradigms to adopt that may protect patients from unintended consequences of being cared for in a digitalized health care system.https://www.sciencedirect.com/science/article/pii/S2949813923001192?via%3Dihu

The Contribution Of Monocytes And Glomerular Endothelial Cells To The Formation Of Endocapillary Hypercellularity In Iga Nephropathy

IgA nephropathy (IgAN) is the most commonly reported primary glomerular disease worldwide. It mainly affects young adults, with many progressing to kidney failure over their lifetime. Five histopathological kidney lesions independently predict a poor prognosis in IgAN (MEST-C score). Published case series highlight the ‘endocapillary hypercellularity’ (E1) lesion as potentially reversible with systemic immunosuppression, improving clinical outcomes. E1 is defined by the obliteration of glomerular capillary lumens by cells that appear to be mostly macrophages, likely to be derived from circulating monocytes. Delineating differences in the transcriptomes of glomerular endothelial cells (GEnCs) and monocyte subsets from patients with and without E1 (E0) to model how they interact may allow identification of safer therapeutic targets. Laser capture microdissection (LCMD) and digital spatial profiling (DSP) using a Nanostring GeoMx were evaluated as tools for enriching GEnC transcripts from formalin fixed paraffin embedded sections of tissue. A JavaScript based tool was written to facilitate DSP on GEnCs. Two pilot experiments (n = 2 and n = 9) were conducted to evaluate the efficacy of DSP against LCMD at enriching for GEnC signals, using single cell deconvolution (SCD) against two different kidney cell atlases. Subsequently a larger DSP experiment (n = 38) was conducted to identify differences between E1 and E0 GEnCs, and the transcriptomes of intra-glomerular CD68 positive macrophages were also profiled. Circulating monocyte subsets were then profiled in E1 and E0 using flow cytometry, cell sorting, and next generation sequencing (NGS) (n=11), and interactions between monocytes and GEnCs were modelled using STRING. The JavaScript function allowed good segmentation on GEnCs and intra-glomerular macrophages for DSP, and SCD showed significant enrichment for both cells relative to neighbouring cell types over LCMD. A cluster of biologically relevant genes were found to be up-regulated in E1 GEnCs including CCL3, CX3CR1, CD44, TNFRSF12A and IL-7, compared to E0. Pathway analysis highlighted pathways related to cell adhesion, apoptosis, cell death and inflammation mediated by IL-27 to be up-regulated among E1 GEnCs (p<0.05, FDR<0.05). Lineage analysis performed on intra-glomerular macrophages in E1 indicated derivation from circulating non-classical monocytes, and flow cytometry found this subset to be contracted in the circulation in E1, suggesting they were being sequestered within glomeruli. NGS of nonclassical monocytes found up-regulated pathways and transcripts related to inflammation and chemokine signalling (including CCR7, CXCR1, CXCR4, CXCL8, CCL3, CCL4, CCL20, IL6 and TNF). Non-classical monocyte-GEnC interaction modelling using STRING identified a cluster of 89 interacting transcripts with an enrichment p value of <1.0e-16. Central to this cluster were inflammatory cytokines, chemokine-chemokine receptors, and cell adhesion transcripts, including LIGHT, BAFF-R, IL-6, CD44, TNF, CCL3, CCL4 and CCR7. Pathways most enriched for within the cluster were related to inflammation (NF-κB, TNF and IL-18 signalling) and immune mediated signalling (toll like receptor signalling). 27/89 transcripts in the cluster already have therapies developed to inhibit them, with TNF, IL-6, BAFFR and LIGHT likely representing high yield therapeutic targets to treat those with IgAN who have E1.</p