Royal College of Surgeons in Ireland

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    Eligibility rates and representativeness of the General Medical Services scheme population in Ireland 2017-2021: a methodological report [version 1; peer review: 2 approved]

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    Background: In Ireland, the means tested General Medical Services (GMS) scheme provides access to a range of healthcare services at no or low cost to approximately one third of the population. Individuals eligible for the GMS scheme are often a focus of research, as a population that account for a large proportion of healthcare services use. The aim of this study is to describe the eligibility rates and representativeness of the GMS scheme population over time, with respect to age group, sex, and geographical area in Ireland.  Methods: Population data was obtained from the Central Statistics Office (CSO), using 2016 Census figures and projected population figures for 2017-2021. GMS eligibility figures for 2016-2021 were obtained from the HSE Primary Care Reimbursement Service (PCRS). GMS eligibility rates and relative rates of eligibility were calculated for 2016-2021 by age group and sex. Additionally, 2016 eligibility rates were calculated by geographical area.  Results: The crude eligibility rate decreased from 36.4% in 2016 to 31.2% in 2020, with a slight increase to 31.6% in 2021. In the 75+ years age group, 78.2% of the total population were eligible for the GMS scheme in 2021. The age group with the lowest rate of eligible individuals was the 25-34 age group, with 19.5% eligible in 2021. The eligibility rate was higher among females compared to males throughout the study period. The highest eligibility rate was seen in Donegal, with a crude rate of 52.8%. Dublin had the lowest rate, with a crude rate of 29.3%.  Conclusions: GMS eligibility varies greatly depending on age, sex, and geographical area, and decreased between 2016 and 2021. This study uses the most up-to-date data available to provide age group, sex and area-based figures for GMS eligibility which may inform planning and conduct of research focusing on GMS-eligible individuals</div

    Temporal enzymatic treatment to enhance the remodeling of multiple cartilage microtissues into a structurally organized tissue

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    Scaffold-free tissue engineering aims to recapitulate key aspects of normal developmental processes to generate biomimetic grafts. Although functional cartilaginous tissues are engineered using such approaches, considerable challenges remain. Herein, the benefits of engineering cartilage via the fusion of multiple cartilage microtissues compared to using (millions of) individual cells to generate a cartilaginous graft are demonstrated. Key advantages include the generation of a richer extracellular matrix, more hyaline-like cartilage phenotype, and superior shape fidelity. A major drawback of aggregate engineering is that individual microtissues do not completely (re)model and remnants of their initial architectures remain throughout the macrotissue. To address this, a temporal enzymatic (chondroitinase-ABC) treatment is implemented to accelerate structural (re)modeling and shown to support robust fusion between adjacent microtissues, enhance microtissue (re)modeling, and enable the development of a more biomimetic tissue with a zonally organized collagen network. Additionally, enzymatic treatment is shown to modulate matrix composition, tissue phenotype, and to a lesser extent, tissue mechanics. This work demonstrates that microtissue self-organization is an effective method for engineering scaled-up cartilage grafts with a predefined geometry and near-native levels of matrix accumulation. Importantly, key limitations associated with using biological building blocks can be alleviated by temporal enzymatic treatment during graft development. </p

    Composite quality measures of abdominal surgery at a population level: systematic review

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    Background: Measurement of surgical quality at a population level is challenging. Composite quality measures derived from administrative and clinical information systems could support system-wide surgical quality improvement by providing a simple metric that can be evaluated over time. The aim of this systematic review was to identify published studies of composite measures used to assess the overall quality of abdominal surgical services at a hospital or population level. Methods: A search was conducted in PubMed and MEDLINE for references describing measurement instruments evaluating the overall quality of abdominal surgery. Instruments combining multiple process and quality indicators into a single composite quality score were included. The identified instruments were described in terms of transparency, justification, handling of missing data, case-mix adjustment, scale branding and choice of weight and uncertainty to assess their relative strengths and weaknesses (PROSPERO registration: CRD42022345074). Results: Of 5234 manuscripts screened, 13 were included. Ten unique composite quality measures were identified, mostly developed within the past decade. Outcome measures such as mortality rate (40 per cent), length of stay (40 per cent), complication rate (60 per cent) and morbidity rate (70 per cent) were consistently included. A major challenge for all instruments is the reliance of valid administrative data and the challenges of assigning appropriate weights to the underlying instrument components. A conceptual framework for composite measures of surgical quality was developed. Conclusion: None of the composite quality measures identified demonstrated marked superiority over others. The degree to which administrative and clinical data influences each composite measure differs in important ways. There is a need for further testing and development of these measures.</p

    Glu298Asp variant of the endothelial nitric oxide synthase gene and acute coronary syndrome or premature coronary artery disease: a systematic review and meta-analysis

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    Introduction: Several published studies have reported an association between the Glu298Asp polymorphism (rs1799983), residing in the endothelial nitric oxide synthase (NOS3) gene, and lower levels of circulating nitric oxide, as well as an increased risk of coronary artery disease (CAD). However, association status of this genetic variant with acute coronary syndrome (ACS) or premature CAD (PCAD) is still unclear. Against this background, we conducted a systematic review and study level meta-analysis to assess the association of the NOS3 Glu298Asp polymorphism with ACS or PCAD. Materials and methods: A comprehensive online search to identify relevant studies was performed on several databases including PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science. The identified studies were stratified into two ancestral subgroups: 'European ancestry' and 'All other ancestries combined'. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random/fixed effects employing a Z test. Results: Out of a total of 195 distinct records identified through online search, 37 articles with 39 different studies, with a total sample size of 27,441 (11,516 cases/15,925 controls) were included for quantitative synthesis. Pooled results suggested significant associations of the NOS3 Glu298Asp polymorphism with ACS or PCAD through dominant as well as allelic genetic models (p ≤ 0.002), primarily driven by the 'All other ancestries combined' subgroup. The 'All other ancestries combined' subgroup demonstrated an additional risk of 36% for ACS or PCAD, through both dominant and allelic genetic models (OR = 1.36, 95%CI = 1.13, 1.63, p = 0.001 and OR = 1.36, 95%CI = 1.14, 1.61, p = 0.0005 respectively). On the other hand, the 'European ancestry' subgroup did not show any significant associations. Sensitivity analysis and a sub-analysis for the myocardial infarction endpoint further supported these observed associations. Conclusions: This meta-analysis indicates towards an association between the NOS3 Glu298Asp polymorphism and ACS or PCAD, predominantly driven by 'All other ancestries combined' subgroup. In contrast, the 'European ancestry' subgroup did not demonstrate any significant association. Further large-scale investigations are required to confirm our derived results.</p

    Familial posterior predominant subcortical band heterotopia caused by a CEP85L missense mutation

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    Lissencephaly comprises a spectrum of cortical malformations caused by disruption of neuronal migration. The lissencephaly spectrum includes agyria defined as cortex lacking gyri with sulci >3cm apart, pachygyria defined as abnormally broad gyri with sulci 1.5-3cm apart, and subcortical band heterotopia (SBH) characterised by a band of heterotopic neurons beneath the cortex, separated by a thin layer of white matter. Lissencephaly has heterogeneous genetic aetiologies, including both single gene mutations (for example, LIS1 and DCX variants) and locus deletions (for example, 17p13.3 deletion causing Miller-Dieker syndrome). A systematic analysis of a large lissencephaly cohort, found a causative mutation in 81% of children, with pathogenic variants in LIS1, DCX, TUBA1A and DYNC1H1 accounting for 69% of all cases. Mutations in specific lissencephaly genes correlated with particular patterns of brain MRI abnormalities: DCX mutations were associated with anterior predominant lissencephaly and LIS1 mutations with posterior predominant lissencephaly. Most unsolved cases had posterior predominant lissencephaly. Heterozygous variants in the CEP85L gene were first identified as a cause of lissencephaly in 2020. Here we highlight the characteristic clinico-radiological CEP85L phenotype in an Irish family with parieto-occipital SBH and focal epilepsy.</p

    Revealing the recent demographic history of Europe via haplotype sharing in the UK Biobank

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    Haplotype-based analyses have recently been leveraged to interrogate the fine-scale structure in specific geographic regions, notably in Europe, although an equivalent haplotype-based understanding across the whole of Europe with these tools is lacking. Furthermore, study of identity-by-descent (IBD) sharing in a large sample of haplotypes across Europe would allow a direct comparison between different demographic histories of different regions. The UK Biobank (UKBB) is a population-scale dataset of genotype and phenotype data collected from the United Kingdom, with established sampling of worldwide ancestries. The exact content of these non-UK ancestries is largely uncharacterized, where study could highlight valuable intracontinental ancestry references with deep phenotyping within the UKBB. In this context, we sought to investigate the sample of European ancestry captured in the UKBB. We studied the haplotypes of 5,500 UKBB individuals with a European birthplace; investigated the population structure and demographic history in Europe, showing in parallel the variety of footprints of demographic history in different genetic regions around Europe; and expand knowledge of the genetic landscape of the east and southeast of Europe. Providing an updated map of European genetics, we leverage IBD-segment sharing to explore the extent of population isolation and size across the continent. In addition to building and expanding upon previous knowledge in Europe, our results show the UKBB as a source of diverse ancestries beyond Britain. These worldwide ancestries sampled in the UKBB may complement and inform researchers interested in specific communities or regions not limited to Britain

    The inflammatory cellular constituents of foetal and infant leptomeninges – a survey of hospital-based autopsies without trauma

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    Introduction: We investigated the possible association of leptomeningeal inflammatory infiltrates and iron deposition in neonates and infants, with the objective of deriving a baseline for reference in forensic cases. Methods: Leptomeninges derived from non-forensic deaths with atraumatic, natural causes was studied. Because of the vastly dissimilar neuroanatomy between newborn infants and older ones, 33 cases were divided into two groups, according to set age groups. Inflammatory cells and iron levels in these were quantified. Results: In group 1 there was a correlation between an increased number of inflammatory cells and the presence of subdural or subarachnoid haemorrhages. Inflammatory cells, albeit reduced in number, were also present in a number of cases in the absence of subdural or subarachnoid haemorrhages. Iron was found in the leptomeninges in several cases in similar quantities, even those without recent haemorrhage. Overall and within the two subgroups, ranges and means of the counts were wide and not significantly different. Conclusion: These findings suggest that inflammatory cells and iron in the leptomeninges can be found in a number of natural and non-traumatic conditions. Further, two cases with no reported neuropathology demonstrated the presence of inflammatory cells and iron. Thus, cautious interpretation of neuropathology found in paediatric forensic cases is recommended.</p

    Total ankle arthroplasty: the future of orthopaedic surgery?

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    The ankle is a complex joint with multiple planes of motion, which we heavily rely on for locomotion, balance and independent functioning. Thus, when arthritis affects the ankle, there are serious consequences, which underline the importance of finding a viable treatment option. One such treatment option, total ankle arthroplasty, has been garnering much attention over the past 30 years as it continues to progress towards a level of effectiveness equivalent to knee and hip replacement surgeries. After many failed generations of implant design, we are finally reaching a level of understanding of how the ankle actually works to make anatomically accurate replacements. The implant design, combined with the knowledge of the injury mechanisms leading to the need for an ankle replacement, have made the success of ankle arthroplasty more likely. For ankle replacement to have the success level of the knee or hip replacement, surgeon technique and proper patient selection must be pursued. If these areas of weakness can be overcome, the total ankle arthroplasty may soon be the first choice among orthopaedic surgeons for management of end-stage ankle arthritis.</p

    Investigating serum extracellular vesicles in cystic fibrosis

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    Background: Extracellular vesicles (EVs) are emerging as biomarkers of disease with diagnostic potential in CF. With the advent of highly effective modulator therapy, sputum production is less common and there is a need to identify novel markers of CF disease progression, exacerbation and response to therapies in accessible fluids such as serum. Methods: We used size exclusion chromatography (SEC) to isolate and characterise EVs from the blood of PWCF of different ages and compared to ultracentrifugation (UC). We used nanoparticle tracking analysis to measure the number of EVs present in serum obtained from children and adults with CF. Mass spectrometry based proteomics was used to characterise protein expression changes between the groups. Results: EVs were successfully isolated in SEC fractions from 250 µl serum from PWCF in greater numbers (p Conclusion: In this pilot study, we performed an initial characterisation of EVs in serum from PWCF demonstrating the potential of serum EVs for further diagnostic investigation.</p

    The MMR vaccine and autism

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    In February 1998, the Lancet published a study by Dr Andrew Wakefield, a British gastroenterologist, which suggested a link between the measles, mumps and rubella (MMR) vaccine as an environmental trigger, and a novel bowel disorder that led to a regressive form of autism. Despite repeated assurances from health professionals and extensive epidemiological studies, which categorically refuted such a link, the controversy sparked a huge public health scare in the United Kingdom. After a decade of controversy and investigation, Dr Wakefield was found guilty of ethical, medical and scientific misconduct in carrying out the study and publishing fraudulent data. It is important for healthcare professionals to be aware of the specifics of the controversy in this multifaceted scandal and the ongoing implications, which have led to a resurgence in cases of measles, mumps and rubella. It is also imperative to question how effectively science is being communicated to the general public to allow them to make better health decisions for their children and themselves. </p

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