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While some speculation surrounds annual private practice incomes of anaesthetists, little is known of the hours of work needed to generate any presumed income (the hourly rate). The benefit maxima of five private medical insurers are published in fee schedules and data on the duration of common operations are now also known. In this study we combined these to generate estimates for hourly rates of reimbursement across 78 common operations in eight surgical subspecialties, for anaesthetists and surgeons. We expected to find significant differences between insurers as a result of market competition, and we expected differences between anaesthetists and surgeons. The median (IQR [range]) rate of reimbursement for anaesthetists was pound167 (132-211 [68-570]).h(-1) with significant variation across subspecialties (p < 0.001); for example, cardiac surgery was best reimbursed at pound283 (257-308 [229-398]).h(-1) and orthopaedics the least at pound146 (133-159 [81-246]).h(-1). Contrary to expectations, the rates of payment to anaesthetists by insurers were similar (p > 0.17). Patterns of reimbursement for surgeons were similar to those for anaesthetists, except that surgeons were reimbursed at about twice the rate. We conclude there is a confluence of insurer reimbursement levels and we discuss potential implications of this finding. Our results also have implications for how incentives between the NHS and private practice, or within a private practice group, might be optimally managed. [ABSTRACT FROM AUTHOR]

A simple algorithm has been produced to assist front line ground ambulance personnel, air ambulance crews, and immediate care doctors attending trauma patients in selecting the most appropriate mode of transport from the incident scene to hospital. [ABSTRACT FROM AUTHOR]

Background: A near miss event (NME) in healthcare is an event that did not happen but would have caused serious harm if it did. The operating room (OR) is prone to risk and incidents, with estimates that 50% of all hospital adverse events occur in the OR, yet reporting of NME is uncommon in the OR., Objective: To carry out a systematic review of studies with mixed methods to establish what is known about NME reporting in the OR., Method: Inclusion criteria will be those studies of mixed methods design, which have been conducted in the OR, with teams of surgeons, anaesthetists or nurses alone or in any combination. Using a publication timeframe of 2001-2023, the following databases were searched: Medline (OVID), CINAHL, Pubmed and Google Scholar. Selected papers for the review were assessed using the Quality Assessment Tool for Studies of Diverse Designs., Results: Fourteen papers were included in the review. NMEs are common occurrences that are underreported in the OR. When NMEs occur in multiples for the same patient, the risk of serious harm increases. Feedback and education about NME helps to improve reporting; ORs with high rates of NME reporting have less serious patient harm events., Discussion: The implications of the findings for improving healthcare safety are discussed and in particular the adoption of the science of Human Factors Ergonomics into healthcare., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Innovative approaches are needed for managing risk and system change in healthcare. This paper presents a case study of a project that took place over two years, taking a systems approach to managing the risk of healthcare acquired infection in an acute hospital setting, supported by an Access Risk Knowledge Platform which brings together Human Factors Ergonomics, Data Science, Data Governance and AI expertise. Evidence for change including meeting notes and use of the platform were studied. The work on the project focused on first systematically building a rich picture of the current situation from a transdisciplinary perspective. This allowed for understanding risk in context and developing a better capability to support enterprise risk management and accountability. From there a linking of operational and risk data took place which led to mapping of the risk pattern in the hospital.

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: People who interact with healthcare services have an ethical and legal right to control their own lives, to make informed decisions, and to consent to what happens to them. For consent to be considered ethically and legally valid, three key criteria must be met: consent must be given voluntarily; people must be sufficiently informed of all options; and people should have capacity to make the decision to give or withhold their consent., Aim: This study set out to explore, through the use of surveys, the perspectives of patients and public in relation to consent., Method: Surveys were developed for patients and the public and administered paper based (patients) and through social media (public)., Results: One hundred and forty surveys were posted to patients, with a 38% response rate; 104 responses were received from the public. Ninety-six percent of patients were satisfied that the decision they made was informed; 100% felt they had made a voluntary decision; 98% felt the clinician seemed knowledgeable about the procedure. What matters most to the public were being informed about the risks associated with the proposed procedure and being assured that whatever choice they make they will receive the best care possible., Conclusions: The results highlight interesting similarities and differences in relation to consent between members of the public thinking about a possible treatment, surgery, or procedure and those patients who have actually been through the process in the past 12 months. Recommendations have been developed on the basis of these findings to co-design improvements in consent practices., (© 2024. The Author(s).)

Introduction: Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity of a novel VUS P93S in Annexin A11 (ANXA11) - an amyotrophic lateral sclerosis/frontotemporal dementia-associated gene - in a corticobasal syndrome kindred. Established ANXA11 mutations cause ANXA11 aggregation, altered lysosomal-RNA granule co-trafficking, and transactive response DNA binding protein of 43 kDa (TDP-43) mis-localization., Methods: We described the clinical presentation and explored the phenotypic diversity of ANXA11 variants. P93S's effect on ANXA11 function and TDP-43 biology was characterized in induced pluripotent stem cell-derived neurons alongside multiomic neuronal and microglial profiling., Results: ANXA11 mutations were linked to corticobasal syndrome cases. P93S led to decreased lysosome colocalization, neuritic RNA, and nuclear TDP-43 with cryptic exon expression. Multiomic microglial signatures implicated immune dysregulation and interferon signaling pathways., Discussion: This study establishes ANXA11 P93S pathogenicity, broadens the phenotypic spectrum of ANXA11 mutations, underscores neuronal and microglial dysfunction in ANXA11 pathophysiology, and demonstrates the potential of cellular models to determine variant pathogenicity., Highlights: ANXA11 P93S is a pathogenic variant. Corticobasal syndrome is part of the ANXA11 phenotypic spectrum. Hybridization chain reaction fluorescence in situ hybridization (HCR FISH) is a new tool for the detection of cryptic exons due to TDP-43-related loss of splicing regulation. Microglial ANXA11 and related immune pathways are important drivers of disease. Cellular models are powerful tools for adjudicating variants of uncertain significance., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: People with disabilities, people experiencing homelessness, and people who have substance use disorders face unique health challenges. Gaps in public health surveillance data limit the identification of public health needs of these groups and data-driven action. This study aimed to identify current practices, challenges, and opportunities for collecting and reporting COVID-19 surveillance data for these populations., Methods: We used a rapid qualitative assessment to explore COVID-19 surveillance capacities. From July through October 2021, we virtually interviewed key informants from the Centers for Disease Control and Prevention, state and local health departments, and health care providers across the United States. We thematically analyzed and contextualized interview notes, peer-reviewed articles, and participant documents using a literature review., Results: We identified themes centered on foundational structural and systems issues that hinder actionable surveillance data for these and other populations that are disproportionately affected by multiple health conditions. Qualitative data analysis of 61 interviews elucidated 4 primary challenges: definitions and policies, resources, data systems, and articulation of the purpose of data collection to these groups. Participants noted the use of multisector partnerships, automated data collection and integration, and data scorecards to circumvent challenges., Conclusions: This study highlights the need for multisector, systematic improvements in surveillance data collection and reporting to advance health equity. Improvements must be buttressed with adequate investment in data infrastructure and promoted through clear communication of how data are used to protect health., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we developed a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrated that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We found that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related protein 1 (DRP1) downstream of DLK, revealing a new mechanism by which DLK can drive apoptosis. Importantly, we show that CRISPR mediated Drp1 depletion protected mouse retinal ganglion neurons from degeneration after optic nerve crush. Our results provide a powerful platform for studying degeneration of human neurons, pinpoint key early events in damage related neural death and new focus for therapeutic intervention.

In neurons, RNA granules are transported along the axon for local translation away from the soma. Recent studies indicate that some of this transport involves hitchhiking of RNA granules on lysosome-related vesicles. In the present study, we leveraged the ability to prevent transport of these vesicles into the axon by knockout of the lysosome-kinesin adaptor BLOC-one-related complex (BORC) to identify a subset of axonal mRNAs that depend on lysosome-related vesicles for transport. We found that BORC knockout causes depletion of a large group of axonal mRNAs mainly encoding ribosomal and mitochondrial/oxidative phosphorylation proteins. This depletion results in mitochondrial defects and eventually leads to axonal degeneration in human induced pluripotent stem cell (iPSC)-derived and mouse neurons. Pathway analyses of the depleted mRNAs revealed a mechanistic connection of BORC deficiency with common neurodegenerative disorders. These results demonstrate that mRNA transport on lysosome-related vesicles is critical for the maintenance of axonal homeostasis and that its failure causes axonal degeneration., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Mutations in progranulin ( GRN ) cause frontotemporal dementia ( GRN -FTD) due to deficiency of the pleiotropic protein progranulin. GRN -FTD exhibits diverse pathologies including lysosome dysfunction, lipofuscinosis, microgliosis, and neuroinflammation. Yet, how progranulin loss causes disease remains unresolved. Here, we report that non-invasive retinal imaging of GRN -FTD patients revealed deficits in photoreceptors and the retinal pigment epithelium (RPE) that correlate with cognitive decline. Likewise, Grn -/- mice exhibit early RPE dysfunction, microglial activation, and subsequent photoreceptor loss. Super-resolution live imaging and transcriptomic analyses identified RPE mitochondria as an early driver of retinal dysfunction. Loss of mitochondrial fission protein 1 (MTFP1) in Grn -/- RPE causes mitochondrial hyperfusion and bioenergetic defects, leading to NF-kB-mediated activation of complement C3a-C3a receptor signaling, which drives further mitochondrial hyperfusion and retinal inflammation. C3aR antagonism restores RPE mitochondrial integrity and limits subretinal microglial activation. Our study identifies a previously unrecognized mechanism by which progranulin modulates mitochondrial integrity and complement-mediated neuroinflammation.

Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote the degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. Here, we show that mRNA transcripts harboring cryptic exons generated de novo proteins in TDP-43-depleted human iPSC-derived neurons in vitro, and de novo peptides were found in cerebrospinal fluid (CSF) samples from patients with ALS or FTD. Using coordinated transcriptomic and proteomic studies of TDP-43-depleted human iPSC-derived neurons, we identified 65 peptides that mapped to 12 cryptic exons. Cryptic exons identified in TDP-43-depleted human iPSC-derived neurons were predictive of cryptic exons expressed in postmortem brain tissue from patients with TDP-43 proteinopathy. These cryptic exons produced transcript variants that generated de novo proteins. We found that the inclusion of cryptic peptide sequences in proteins altered their interactions with other proteins, thereby likely altering their function. Last, we showed that 18 de novo peptides across 13 genes were present in CSF samples from patients with ALS/FTD spectrum disorders. The demonstration of cryptic exon translation suggests new mechanisms for ALS/FTD pathophysiology downstream of TDP-43 dysfunction and may provide a potential strategy to assay TDP-43 function in patient CSF.