Quality assurance in surgical trials of arteriovenous grafts for haemodialysis: A systematic review, a narrative exploration and expert recommendations.

BACKGROUND: Introducing new procedures and challenging established paradigms requires well-designed randomised controlled trials (RCT). However, RCT in surgery present unique challenges with much of treatment tailored to the individual patient circumstances, refined by experience and limited by organisational factors. There has been considerable debate over the outcomes of arteriovenous grafts (AVG) compared to AVF, but any differences may reflect differing practice and potential variability. It is essential, therefore, when considering an RCT of a novel surgical procedure or device that quality assurance (QA) is defined for both the new approach and the comparator. The aim of this systematic review was to evaluate the QA standards performed in RCT of AVG using a multi-national, multi-disciplinary approach and propose an approach for future RCT. METHOD: The methods of this have been previously registered (PROSPERO: CRD420234284280) and published. In summary, a four-stage review was performed: identification of RCT of AVG, initial review, multidisciplinary appraisal of QA methods and reconciliation. QA measures were sought in four areas - generic, credentialing, standardisation and monitoring, with data abstracted by a multi-national, multi-speciality review body. RESULTS: QA in RCT involving AVG in all four domains is highly variable, often sub-optimally described and has not improved over the past three decades. Few RCT established or defined a pre-RCT level of experience, none documented a pre-trial education programme, or had minimal standards of peri-operative management, no study had a defined pre-trial monitoring programme, and none assessed technical performance. CONCLUSION: QA in RCT is a relatively new area that is expanding to ensure evidence is reliable and reproducible. This review demonstrates that QA has not previously been detailed, but can be measured in surgical RCT of vascular access, and that a four-domain approach can easily be implemented into future RCT.

A practical review of barriers and challenges to a definitive randomised trial of grafts versus fistula.

A definitive randomised controlled trial of arteriovenous fistula (AVF) versus arteriovenous grafts (AVG) has been advocated for more than a decade, but as yet, none has been completed. The aim of this article is to summarise the theoretical barriers, review the difficulties in trial design and practicalities that have thus far prevented this from occurring.

De novo assembly and annotation of the Patagonian toothfish (Dissostichus eleginoides) genome.

BACKGROUND: Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae. Juveniles occupy progressively deeper waters as they mature and grow, and adults have been caught as deep as 2500 m, living on or in just above the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. As apex predators, they are a key part of the food web, feeding on a variety of prey, including krill, squid, and other fish. Despite its importance, genomic sequence data, which could be used for more accurate dating of the divergence between Patagonian and Antarctic toothfish, or establish whether it shares adaptations to temperature with fish living in more polar or equatorial climes, has so far been limited. RESULTS: A high-quality D. eleginoides genome was generated using a combination of Illumina, PacBio and Omni-C sequencing technologies. To aid the genome annotation, the transcriptome derived from a variety of toothfish tissues was also generated using both short and long read sequencing methods. The final genome assembly was 797.8 Mb with a N50 scaffold length of 3.5 Mb. Approximately 31.7% of the genome consisted of repetitive elements. A total of 35,543 putative protein-coding regions were identified, of which 50% have been functionally annotated. Transcriptomics analysis showed that approximately 64% of the predicted genes (22,617 genes) were found to be expressed in the tissues sampled. Comparative genomics analysis revealed that the anti-freeze glycoprotein (AFGP) locus of D. eleginoides does not contain any AFGP proteins compared to the same locus in the Antarctic toothfish (Dissostichus mawsoni). This is in agreement with previously published results looking at hybridization signals and confirms that Patagonian toothfish do not possess AFGP coding sequences in their genome. CONCLUSIONS: We have assembled and annotated the Patagonian toothfish genome, which will provide a valuable genetic resource for ecological and evolutionary studies on this and other closely related species.

Patient-Centred, Technology-Based Interventions for High Treatment Burden: An Overview of the State of the Art.

This study provides an overview of recent efforts to develop technology-based interventions for patients with high treatment burden. Adoption of a technological intervention for high treatment burden will depend on a range of factors, including: the reliability and accessibility of the technology, patient factors including age, socio-economic factors, technology literacy, overall health status and personal priorities - as well as the perceived benefits provided by the technology intervention, from the perspectives of both patients and clinicians.

What are the observed procedural costs of vascular access surgery? Protocol for a systematic review.

INTRODUCTION: A central component in the introduction of a novel surgical procedure or technique is an evaluation of its cost efficiency when compared with a benchmark standard of care. Accurate assessment of costs is thus essential in ensuring appropriate allocation of resources within a healthcare system. The treatment of kidney failure requires a significant volume of resources, and vascular access provision is the main modifiable cost. The costs of providing this service are obscured by generic NHS reference costs, which lack adequate granularity to allow meaningful comparisons between treatments. The aim of this systematic review will be to assess the reporting of procedural costs in all published economic analyses of vascular access surgery and perform a comparison of the reported procedural costs involved in arteriovenous fistula (AVF) and arteriovenous graft (AVG) creation. This will provide an estimate as to the accuracy of the NHS reference costs in this field. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A systematic search will be performed of the MEDLINE, Embase and Cochrane databases to identify full-text economic analyses of vascular access for haemodialysis in which the procedural cost of AVF or AVG creation is reported. Publications in English from 1 January 2000 to 30 August 2023, will be eligible for inclusion. Studies will be selected by title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Studies not reporting the procedural costs of surgery will be excluded. Data collected will pertain to procedural costs of AVF and AVG creation. Costs will be adjusted to a common currency using a gross domestic product (GDP) deflator index and conversion rates based on purchasing power parities for GDP. Comparison with NHS reference costs will indicate their reliability for use in future economic analyses in this field. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023458779.

Association between major histocompatibility complex haplotypes and susceptibility of unvaccinated and vaccinated cattle to paratuberculosis.

Bovine Johne's disease (BJD) or paratuberculosis is caused by Mycobacterium avium spp. paratuberculosis (MAP) and is a worldwide problem among domestic and wild ruminants. While vaccines are available, natural differences in background immunity between breeds within species and between individuals within herds suggest that genetic differences may be able to be exploited in marker-assisted selection as an aid to disease control. The major histocompatibility complex (MHC) is an important component in immune recognition with considerable genetic variability. In this study, associations between the MHC and resistance to BJD were explored in dairy cattle across two herds in which some of the cattle had been vaccinated with Silirum® (n = 540 cows). A BJD susceptible animal was exposed to MAP and became infected, while a resistant animal was exposed but did not become infected. There are different ways to define both exposure and infection, with different levels of stringency, therefore many classifications of the same set of animals are possible and were included in the analysis. The polymorphic regions of major histocompatibility complex class I (MHC I) and class II (MHC II) genes were amplified from the genomic DNA by PCR and sequenced, targeting exons 2 and 3 of the classical and non-classical MHC I genes and exon 2 from the DRB3, DQA1, DQA2 + 3 and DQB MHC II genes. The frequencies of MHC I and MHC II haplotypes and alleles were determined in susceptible and resistant populations. In unvaccinated animals, seven MHC I haplotypes and seven MHC II haplotypes were associated with susceptibility while two MHC I and six MHC II haplotypes were associated with resistance (P < 0.05). In vaccinated animals, two MHC I and three MHC II haplotypes were associated with susceptibility, while one MHC I and two MHC II haplotypes were associated with resistance (P < 0.05). The alleles in significant haplotypes were also identified. Case definitions with higher stringency resulted in fewer animals being included in the analyses, but the power to detect an association was not reduced and there was an increase in strength and consistency of associations. Consistent use of stringent case definitions is likely to improve agreement in future association studies.

Early-cannulation arteriovenous grafts: Multidisciplinary learning is essential to optimize outcomes.

BACKGROUND: It is likely that there will be an increasing role for early-cannulation arteriovenous grafts (ecAVG) with a wider recognition of the need to tailor vascular access to avoid futile procedures and unnecessary TCVC. However, experience of these products is not common and limited to early surgical adopters, with little information on the systemic changes and multi-disciplinary care needed to optimize outcomes. The aim of this study was to report the impact of a multi-disciplinary approach on quantifiable outcomes. METHODS: A retrospective analysis of a prospectively maintained database of 295 ecAVG implanted over an 8-year time-period was performed. Indicative outcomes were chosen to reflect nephrology (patient selection), nursing care (cannulation complications of infection and pseudoaneurysm) and radiology (thrombosis) on cumulative impact (functional patency) over three distinct time periods. RESULTS: The incidence of ecAVG increased 10-fold over the three time periods. The use of ecAVG changed significantly from salvage tertiary access to TCVC avoidance and salvage of existing AVF. Nursing complications reduced markedly with significantly fewer over-cannulation episodes and pseudo-aneurysms. With an improved pro-active surveillance programme, the time to first thrombosis doubled and the risk of thrombosis halved. Ultimately this resulted in significantly improved functional patency with a risk of ecAVG loss less than one-third by the last time-period. CONCLUSIONS: All aspects of ecAVG use require scrutiny and critical appraisal. Failure or success is not simply achieved by performing good technical surgery with an efficacious product, but by the care taken across a wide range of elements spanning case selection, implantation, use and maintenance.

Bayesian Disease Mapping to Identify High-Risk Population for Oral Cancer: A Retrospective Spatiotemporal Analysis.

Objectives: Bayesian mapping is an effective spatiotemporal approach to identify high-risk geographic areas for diseases and has not been used to identify oral cancer hotspots in Australia previously. This retrospective disease mapping study was undertaken to identify the oral cancer trends and patterns within the Queensland state in Australia. Methods: This study included data obtained from Queensland state Cancer Registry from 1982 to 2018. Domains mapped included the oral cancer incidence and mortality in Queensland (QLD). Local government areas (LGAs) and suburbs were utilized as geographical units for the estimation using Bayesian mapping approach. Results: Of the 78 LGAs, 21 showed high-oral cancer incidence as measured using higher median smoothed incidence risk (SIR), above the state average. Specifically, nine LGAs within predominantly rural areas had SIR above 100% of the state average. Of these, only one LGA (Mount Isa City) had a median smoothed SIR and 95% CI of 2.61 (2.14-3.15) which was constantly above 100% of the state average. Furthermore, mortality risk estimated using smoothed mortality risk (SMR), were significantly higher than the state average in 31 LGAs. Seventeen LGAs had a median SMR above 100% of the state average while three LGAs had the highest overall, 3- and 5-year mortality risks. Considering the 95% credible interval which is indicative of the uncertainty around the estimates, three LGAs had the highest overall mortality risks-Yarrabah Aboriginal Shire (3.80 (2.16-6.39)), Cook Shire (3.37 (2.21-5.06)), and Mount Isa City (3.04 (2.40-3.80)). Conclusion: Bayesian disease mapping approach identified multiple incidence and mortality hotspots within regional areas of the Queensland. Findings from our study can aid in designing targeted public health screening and interventions for primary prevention of oral cancer in regional and remote communities.

Effect of restricted feeding on hen performance, egg quality and organ characteristics of individual laying hens.

This study was to assess the impact of permanent or temporary restricted feeding on laying hen production traits, physiology, and egg quality. Two hundred and forty individually housed ISA Brown hens were monitored across 2 phases, assigned to 3 treatments: ad libitum feeding (ALF), temporary restricted feeding (TRF) and permanent restricted feeding (PRF), n = 80 hens per treatment. In Phase 1 (P1), 22 to 40 weeks, the TRF and PRF hens were offered 115 g of feed daily. In Phase 2 (P2), 41 to 46 weeks, the TRF hens were transitioned to ALF status while the ALF and PRF hens remained as in P1. From 35 to 40 weeks, eggs were collected once weekly from 15 hens per treatment and assessed for differences in albumen, yolk, and shell variables. At 45 weeks, 10 hens each from the ALF and PRF groups were euthanized and differences in organ characteristics were assessed. In P1, feed intake, feed to egg conversion ratio and body weight (BW) change were lower (P < 0.01), while albumen height and Haugh unit were higher (P < 0.01) in both PRF and TRF hen treatments compared to hens allocated the ALF treatment. In P2, TRF and ALF hens had a higher egg production and egg mass than PRF (P < 0.01) than ALF. Body weight change in P2 was higher in TRF and similar in both ALF and PRF, while feed intake and feed conversion ratio were higher in TRF followed by ALF and least in the PRF treatment group (P < 0.01). At 45 weeks ALF hens had a greater abdominal fat pad weight and fatty liver haemorrhagic syndrome lesion score compared to PRF. Restricting hens to 115 g of feed per day from point of lay restrained BW, improved feed conversion ratio and albumen quality and reduced abdominal fat pad deposition and clinical signs of fatty liver haemorrhagic syndrome in individually housed laying hens.

Quality assurance in surgical trials of arteriovenous grafts for haemodialysis: protocol for a systematic review.

INTRODUCTION: Decisions regarding the optimal vascular access for haemodialysis patients are becoming increasingly complex, and the provision of vascular access is open to variations in systems of care as well as surgical experience and practice. Two main surgical options are recognised: arteriovenous fistula and arteriovenous graft (AVG). All recommendations regarding AVG are based on a limited number of randomised controlled trials (RCTs). It is essential that when considering an RCT of a surgical procedure, an appropriate definition of quality assurance (QA) is made for both the new approach and the comparator, otherwise replication of results or implementation into clinical practice may differ from published results. The aim of this systematic review will be to assess the methodological quality of RCT involving AVG, and the QA measures implemented in delivering interventions in these trials. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A systematic search will be performed of the MEDLINE, Embase and Cochrane databases to identify relevant literature. Studies will be selected by title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data collected will pertain to generic measures of QA, credentialing of investigators, procedural standardisation and performance monitoring. Trial methodology will be compared against a standardised template developed by a multinational, multispecialty review body with experience in vascular access. A narrative approach will be taken to synthesise and report data. ETHICS AND DISSEMINATION: Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations, with the ultimate aim of providing recommendations for future RCT of AVG design.

Quantitative trait and transcriptome analysis of genetic complexity underpinning cardiac interatrial septation in mice using an advanced intercross line.

Unlike single-gene mutations leading to Mendelian conditions, common human diseases are likely to be emergent phenomena arising from multilayer, multiscale, and highly interconnected interactions. Atrial and ventricular septal defects are the most common forms of cardiac congenital anomalies in humans. Atrial septal defects (ASD) show an open communication between the left and right atria postnatally, potentially resulting in serious hemodynamic consequences if untreated. A milder form of atrial septal defect, patent foramen ovale (PFO), exists in about one-quarter of the human population, strongly associated with ischaemic stroke and migraine. The anatomic liabilities and genetic and molecular basis of atrial septal defects remain unclear. Here, we advance our previous analysis of atrial septal variation through quantitative trait locus (QTL) mapping of an advanced intercross line (AIL) established between the inbred QSi5 and 129T2/SvEms mouse strains, that show extremes of septal phenotypes. Analysis resolved 37 unique septal QTL with high overlap between QTL for distinct septal traits and PFO as a binary trait. Whole genome sequencing of parental strains and filtering identified predicted functional variants, including in known human congenital heart disease genes. Transcriptome analysis of developing septa revealed downregulation of networks involving ribosome, nucleosome, mitochondrial, and extracellular matrix biosynthesis in the 129T2/SvEms strain, potentially reflecting an essential role for growth and cellular maturation in septal development. Analysis of variant architecture across different gene features, including enhancers and promoters, provided evidence for the involvement of non-coding as well as protein-coding variants. Our study provides the first high-resolution picture of genetic complexity and network liability underlying common congenital heart disease, with relevance to human ASD and PFO.

Oral cavity and oropharyngeal carcinoma disparities in age and survival in Indigenous and non-Indigenous populations of Queensland.

OBJECTIVES: To investigate the risk and prognosis of oral squamous cell carcinoma (SCC) between Indigenous and non-Indigenous populations of Queensland. MATERIALS AND METHODS: Retrospective analysis of data from the Queensland Cancer Registry (QCR) between the years 1982-2018. Main outcome measures were age at diagnosis and cumulative survival to compare the risk and prognosis of oral SCC between the populations. RESULTS: 9424 patients with self-declared ethnicity were identified with oral SCC from the QCR, with a male to female ratio of 2.56:1. Of these patients, 9132 were non-Indigenous (96.9%) and 292 Indigenous (3.1%). Indigenous people were significantly younger at diagnosis (mean (SD) age 54.3 (10.1) years), compared to 62.0 (12.1) years in non-Indigenous people. Mean survival in the full cohort was 4.3 years (SD: 5.6), with Indigenous people presenting a significant shorter mean survival of 2.0 years (SD: 3.5) when compared with 4.4 years (SD: 5.7) in non-Indigenous people (p < 0.001). CONCLUSIONS: Indigenous Australians are diagnosed at a significantly younger age and present with worse survival and poorer prognosis. Due to missing variables in the Queensland Cancer Registry, it is not possible in the current study to ascertain the scientific or social reasons behind these disparities. CLINICAL RELEVANCE: Results from this study can inform public policy and raise awareness in Queensland regarding disparity in oral cancer prognosis.

Influence of time between surgery and adjuvant radiotherapy on prognosis for patients with head and neck squamous cell carcinoma: A systematic review.

The timing of postoperative radiotherapy following surgical intervention in patients with head and neck cancer remains a controversial issue. This review aims to summarize findings from available studies to investigate the influence of time delays between surgery and postoperative radiotherapy on clinical outcomes. Articles between 1 January 1995 and 1 February 2022 were sourced from PubMed, Web of Science, and ScienceDirect. Twenty-three articles met the study criteria and were included; ten studies showed that delaying postoperative radiotherapy might negatively impact patients and lead to a poorer prognosis. Delaying the start time of radiotherapy, 4 weeks after surgery did not result in poorer prognoses for patients with head and neck cancer, although delays beyond 6 weeks might worsen patients' overall survival, recurrence-free survival, and locoregional control. Prioritization of treatment plans to optimize the timing of postoperative radiotherapy regimes is recommended.

Predicting oral cancer survival-Development and validation of an Asia-Pacific nomogram.

BACKGROUND: Nomograms are graphical calculating devices that predict response to treatment during cancer management. Oral squamous cell carcinoma (OSCC) is a lethal and deforming disease of rising incidence and global significance. The aim of this study was to develop a nomogram to predict individualized OSCC survival using a population-based dataset obtained from Queensland, Australia and externally validated using a cohort of OSCC patients treated in Hong Kong. METHODS: Clinico-pathological data for newly diagnosed OSCC patients, including age, sex, tumour site and grading, were accessed retrospectively from the Queensland Cancer Registry (QCR) in Australia and the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Multivariate Cox proportional hazard regression was used to construct overall survival (OS) and cancer-specific survival (CSS) prediction models. Nomograms were internally validated using 10-fold cross validation, and externally validated against the Hong Kong dataset. RESULTS: Data from 9885 OSCC patients in Queensland and 465 patients from Hong Kong were analysed. All clinico-pathological variables significantly influenced survival outcomes. Nomogram calibration curves demonstrated excellent agreement between predicted and actual probability for Queensland patients. External validation in the Hong Kong population demonstrated slightly poorer nomogram performance, but predictive power remained strong. CONCLUSION: Based upon readily available data documenting patient demographic and clinico-pathological variables, predictive nomograms offer pragmatic aid to clinicians in individualized treatment planning and prognosis assessment in contemporary OSCC management.

Recruitment into randomised trials of arteriovenous grafts: A systematic review.

Although randomised controlled trials (RCT) are considered the optimal form of evidence, there are relatively few in surgery. Surgical RCT are particularly likely to be discontinued with poor recruitment cited as a leading reason. Surgical RCT present challenges over and above those seen in drug trials as the treatment under study may vary between procedures, between surgeons in one unit, and between units in multi-centred RCT. The most contentious and debated area of vascular access remains the role of arteriovenous grafts, and thus the quality of the data that is used to support opinions, guidelines and recommendations is critical. The aim of this review was to determine the extent of variation in the planning and recruitment in all RCT involving AVG. The findings of this are stark: there have been only 31 RCT performed in 31 years, the vast majority of which exhibited major limitations severe enough to undermine the results. This underlines the need for better quality RCT and data, and further inform the design of future studies. Perhaps most fundamental is the planning for a RCT that accounts for the intended population, the uptake of a RCT and the attrition for the significant co-morbidity in this population.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: associations with mortality in a haemodialysis cohort.

Background: Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a coronavirus disease 2019 (COVID-19) infection subpopulation. Methods: A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland during 2010-21. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan-Meier and Cox proportional hazards analyses were used to assess mortality associations. Results: In 1720 haemodialysis patients over a median of 21.9 (interquartile range 9.1-42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥8.23) versus quartile 1 (NLR <3.12) 1.63, 95% confidence interval (CI) 1.32-2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53-6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34-2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48-14.92 and PLR: aHR 3.40, 95% CI 1.02-11.36; for highest vs lowest quartiles). Conclusions: NLR is strongly associated with mortality in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients.

The Impact of Surgery on Circulating Malignant Tumour Cells in Oral Squamous Cell Carcinoma.

IMPORTANCE: The extent to which surgical management of oral squamous cell carcinoma (OSCC) disseminates cancer is currently unknown. OBJECTIVE: To determine changes in numbers of malignant cells released into systemic circulation immediately following tumour removal and over the first seven post-operative days. DESIGN: An observational study from March 2019 to February 2021. SETTING: This study was undertaken at Queen Mary University Hospital, Hong Kong. PARTICIPANTS: Patients with biopsy-proven oral SCC were considered for eligibility. Patients under 18 years of age, pregnant or lactating women and those unable to understand the study details or unable to sign the consent form were excluded. Twenty-two patients were enrolled (12 male and 10 female) with mean age of 65.5 years. INTERVENTION: Primary tumour management was performed in accord with multi-disciplinary team agreement. Anaesthesia and post-operative care were unaltered and provided in accord with accepted clinical practice. MAIN OUTCOMES AND MEASURES: Three types of malignant cells detected in peripheral blood samples were enumerated and sub-typed based on the presence of chromosomal aneuploidy and immunohistochemical characteristics. To test the hypothesis that malignant cells are released by surgery, the numbers of single circulating tumour cells (CTCs), circulating tumour microemboli (CTM) and circulating endothelial cells (CTECs) were recorded pre-operatively, upon tumour removal and the second and seventh post-operative days. RESULTS: Of a potential 88 data collection points, specimens were not obtainable in 12 instances. Tumour removal resulted in a statistically significant increase in CTCs and a non-statistically significant rise in CTMs. CTCs, CTMs and CTECs were detected in the majority of patients up to the seventh post-operative day. Individual patients demonstrated striking increases in post-operative CTCs and CTECs numbers. CONCLUSIONS/RELEVANCE: Surgical management of OSCC has a significant impact on the systemic distribution of cancer cells. Malignant cells persisted post-operatively in a manner independent of recognised staging methods suggesting differences in tumour biology between individuals. Further investigation is warranted to determine whether circulating malignant cell enumeration can be used to refine risk stratification for patients with OSCC.

Oral cancer in Australia: Rising incidence and worsening mortality.

BACKGROUND: Oral cancer, predominantly squamous cell carcinoma (SCC), is a lethal and deforming disease of rising incidence. Although largely preventable by eliminating harmful tobacco and alcohol risk factor behaviour, 5-year survival rates remain around 50%, primarily due to late presentation of advanced stage disease. Whilst low socio-economic status, regional and remote location and indigenous status are associated with head and neck cancer in general, detailed incidence and demographic data for oral SCC in Australia are limited. This study aimed to characterise the Queensland population at risk of oral SCC development. METHODS: Following ethical approval, the Queensland Cancer Register (QCR) dataset was analysed to determine patterns of incidence, anonymised patient demographics, clinical presentation and outcome data for oral SCC cases diagnosed between 1982 and 2018. RESULTS: Data from 9887 patients were obtained. Mean age at diagnosis was 64.55 years, with a male-to-female ratio of 2.51:1; males were diagnosed at a younger age (p < 0.001). At study census date, 59% of patients had died, with females demonstrating longer mean survival (p < 0.001). Clinicopathological data confirmed that SCC most commonly arose from tongue sites (49%) and, whilst tumours were predominantly moderately differentiated in nature (63%), patients with poorly differentiated carcinomas exhibited shortest survival times (p < 0.05). Over the 36-year study period, the number of diagnoses increased 4.49-fold, whilst the number of deaths increased 19.14-fold. CONCLUSION: Oral SCC poses a significant and growing healthcare problem in Queensland. In the absence of national screening, characterising the high-risk oral SCC population facilitates pragmatic opportunities to raise disease awareness, to deliver targeted screening and effective primary prevention strategies, and to provide early interventional treatment intervention to reduce disease mortality and morbidity.

Red Meat Derived Glycan, N-acetylneuraminic Acid (Neu5Ac) Is a Major Sialic Acid in Different Skeletal Muscles and Organs of Nine Animal Species-A Guideline for Human Consumers.

Sialic acids (Sias) are acidic monosaccharides and red meat is a notable dietary source of Sia for humans. Among the Sias, N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN) play multiple roles in immunity and brain cognition. On the other hand, N-glycolylneuraminic acid (Neu5Gc) is a non-human Sia capable of potentiating cancer and inflammation in the human body. However, their expression within the animal kingdom remains unknown. We determined Neu5Ac and KDN in skeletal muscle and organs across a range (n = 9) of species using UHPLC and found that (1) caprine skeletal muscle expressed the highest Neu5Ac (661.82 ± 187.96 µg/g protein) following by sheep, pig, dog, deer, cat, horse, kangaroo and cattle; (2) Among organs, kidney contained the most Neu5Ac (1992−3050 µg/g protein) across species; (3) ~75−98% of total Neu5Ac was conjugated, except for in dog and cat muscle (54−58%); (4) <1% of total Sia was KDN, in which ~60−100% was unconjugated, with the exception of sheep liver and goat muscle (~12−25%); (5) Neu5Ac was the major Sia in almost all tested organs. This study guides consumers to the safest red meat relating to Neu5Ac and Neu5Gc content, though the dog and cat meat are not conventional red meat globally.

Validation of a vascular access specific quality of life measure (VASQoL).

BACKGROUND: A self-administered 11 item vascular access specific quality of life measure (VASQoL) was previously derived from detailed qualitative interviews with adult patients with kidney failure who have experienced vascular access using the Capabilities Approach as a theoretical base. This study reports the psychometric validation of the VASQoL measure including its reliability, content validity and responsiveness to change. METHODS: Cognitive interviews were conducted with 23 adult patients with kidney failure after completion of the VASQoL measure. Focus group discussion with a vascular access professional multidisciplinary team was undertaken (n = 8) and subsequently a further 101 adult kidney failure patients with vascular access (TCVC, AVF or AVG) completed the digital VASQoL measure, EQ-5D and SF-36 questionnaires in a longitudinal study with prospectively recorded vascular access events. RESULTS: Transcript analysis of cognitive interviews after VASQoL completion indicated that the content was comprehensive and well understood by participants. Assessment of Internal reliability for the VASQoL measure was high (Cronbach's alpha 0.858). Test-retest reliability of the overall VASQoL measure was high (intra class correlation coefficient 0.916). In those patients who experienced a vascular access event, significant differences were observed in paired analysis of the VASQoL physical domain questions and vascular access function domain questions and in the EQ-5D usual activities, pain and anxiety domains. In those with no vascular access event, variation was observed in longitudinal analysis in VASQoL questions relating to worry about VA function and capability domains, whilst no variation was observed in the EQ5D measure. CONCLUSION: The VASQoL measure has good internal consistency, test-retest reliability, convergent validity and responsiveness to change for clinically relevant vascular access outcomes. This provides a validated, vascular access specific quality of life measure that can be used in future trials of vascular access, evaluation of new technologies and routine use as a patient reported outcome measure (PROM).