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Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to study the genotype distribution of FCS-causing genes in the United Kingdom, genotype-phenotype correlation, and clinical differences between FCS and multifactorial chylomicronemia syndrome (MCS)., Methods: The study included 154 patients (FCS, 74; MCS, 80) from the UK FCS national registry and the UK arm of the FCS International Quality Improvement and Service Evaluation Project., Results: FCS was relatively common in non-Europeans and those with parental consanguinity ( P <0.001 for both). LPL variants were more common in European patients with FCS (European, 64%; non-European, 46%), while the genotype was more diverse in non-European patients with FCS. Patients with FCS had a higher incidence compared with patients with MCS of acute pancreatitis (84% versus 60%; P =0.001), recurrent pancreatitis (92% versus 63%; P <0.001), unexplained abdominal pain (84% versus 52%; P <0.001), earlier age of onset (median [interquartile range]) of symptoms (15.0 [5.5-26.5] versus 34.0 [25.2-41.7] years; P <0.001), and of acute pancreatitis (24.0 [10.7-31.0] versus 33.5 [26.0-42.5] years; P <0.001). Adverse cardiometabolic features and their co-occurrence was more common in individuals with MCS compared with those with FCS ( P <0.001 for each). Atherosclerotic cardiovascular disease was more prevalent in individuals with MCS than those with FCS ( P =0.04). However, this association became nonsignificant after adjusting for age, sex, and body mass index. The prevalence of pancreatic complications and cardiometabolic profile of variant-positive MCS was intermediate between FCS and variant-negative MCS., Conclusions: The frequency of gene variant distribution varies based on the ethnic origin of patients with FCS. Patients with FCS are at a higher risk of pancreatic complications while the prevalence of atherosclerotic cardiovascular disease is lower in FCS compared with MCS. Carriers of heterozygous pathogenic variants have an intermediate phenotype between FCS and variant-negative MCS., Competing Interests: H. Soran received personal fees from Amgen, Akcea, Synageva, Napp, Novartis, Takeda, Sanofi, Pfizer, and Kowa and research grants and donations from Akcea, Pfizer, Merck Sharp & Dohme, Amgen, Genzyme-Sanofi, Synageva, Amryt, Synageva, and Alexion. A.S. Wierzbicki is a site investigator on trials from Akcea and Regeneron; received royalties from Elsevier for a book on familial chylomicronemia syndrome; and is a board member for the Familial Hyperlipidaemia group, Europe. D. Datta received honoraria for advisory board from Swedish Orphan Biovitrum. N. Forrester received honoraria for presentations from SOBI. Y. Teoh received speakers fee from Daiichi Sankyo and Amarin. P. Downie received honoraria from SOBI, Novartis, Amgen, and Daiichi Sankyo. R.A. Hegele received consulting fees from Acasti, Aegerion, Akcea/Ionis, Amgen, Arrowhead, HLS Therapeutics, Pfizer, Novartis, Regeneron, Sanofi, and UltraGenyx. The other authors report no conflicts.

Background and Aims: Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it., Methods: A retrospective validation study was conducted using data from 151 patients comprising 75 FCS and 76 MCS patients. All participants had undergone genetic testing for genes implicated in FCS. Validation was performed by standard methods. Additional variables were identified from clinical data by logistic regression analysis., Results: At the recommended FCS score threshold ≥10 points, the sensitivity and specificity of the score in the UK population were 96% and 75%, respectively. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.88 (95% CI 0.83-0.94, p < 0.001). This study identified non-European (predominantly South Asian) ethnicity, parental consanguinity, body mass index (BMI) < 25 kg/m 2 , and recurrent pancreatitis as additional positive predictors, while BMI >30 kg/m 2 was found to be a negative predictor for FCS. However, inclusion of additional FCS predictors had no significant impact on performance of standard FCS score., Conclusions: Our study validates the FCS score in the UK population to distinguish FCS from MCS. While additional FCS predictors were identified, they did not improve further the score diagnostic performance., Competing Interests: Declaration of competing interest HS: Received personal fees from Amgen, Akcea, Synageva, NAPP, Novartis, Takeda, Sanofi, Pfizer, SOBI and Kowa and research grants and donations from Akcea, Pfizer, MSD, Amgen, Genzyme-Sanofi, Synageva, Amryt, Synageva and Alexion. ASW: Received grants from Akcea, Regeneron; Royalties from Elsevier and is a board member for familial hyperlipidaemia group, Europe. DD: Received honoraria for advisory boards from SOBI. NF: Received honoraria for presentations from SOBI. YT: Received speakers fee from Daiichi Sankyo and Amarin. PD: Received honoraria from SOBI, NOVARTIS, AMGEN and Daiichi Sankyo. PM: Participated on a Data Safety Monitoring Board and Advisory Board for Ionis, AKCEA, AMRYT, AMARIN, Ultragenix AG: received research grants from AMGEN, SANOFI, AMRYT, ULTRAGENYX, Consulting fee or honoraria from AMGEN, SANOFI, AMRYT, ULTRAGENYX, NOVARTIS, AKCEA, SERVIER. BB, SK, CD, AJ, FJ, MM, HD, PH, MM, AA, DO, PND: None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We multiply ascertained the BRCA1 pathogenic missense variant c.5207T > C; p.Val1736Ala (V1736A) in clinical investigation of breast and ovarian cancer families from Orkney in the Northern Isles of Scotland, UK. We sought to investigate the frequency and clinical relevance of this variant in those of Orcadian ancestry as an exemplar of the value of population cohorts in clinical care, especially in isolated populations. Oral history and birth, marriage and death registrations indicated genealogical linkage of the clinical cases to ancestors from the Isle of Westray, Orkney. Further clinical cases were identified through targeted testing for V1736A in women of Orcadian ancestry attending National Health Service (NHS) genetic clinics for breast and ovarian cancer family risk assessments. The variant segregates with female breast and ovarian cancer in clinically ascertained cases. Separately, exome sequence data from 2088 volunteer participants with three or more Orcadian grandparents, in the ORCADES research cohort, was interrogated to estimate the population prevalence of V1736A in Orcadians. The effects of the variant were assessed using Electronic Health Record (EHR) linkage. Twenty out of 2088 ORCADES research volunteers (~1%) carry V1736A, with a common haplotype around the variant. This allele frequency is ~480-fold higher than in UK Biobank participants. Cost-effectiveness of population screening for BRCA1 founder pathogenic variants has been demonstrated at a carrier frequency below the ~1% observed here. Thus we suggest that Orcadian women should be offered testing for the BRCA1 V1736A founder pathogenic variant, starting with those with known Westray ancestry., (© 2023. The Author(s).)

NHS genetics centres in Scotland sought to investigate the Genomics England 100,000 Genomes Project diagnostic utility to evaluate genome sequencing for in rare, inherited conditions. Four regional services recruited 999 individuals from 394 families in 200 rare phenotype categories, with negative historic genetic testing. Genome sequencing was performed at Edinburgh Genomics, and phenotype and sequence data were transferred to Genomics England for variant calling, gene-based filtering and variant prioritisation. NHS Scotland genetics laboratories performed interpretation, validation and reporting. New diagnoses were made in 23% cases - 19% in genes implicated in disease at the time of variant prioritisation, and 4% from later review of additional genes. Diagnostic yield varied considerably between phenotype categories and was minimal in cases with prior exome testing. Genome sequencing with gene panel filtering and reporting achieved improved diagnostic yield over previous historic testing but not over now routine trio-exome sequence tests. Re-interpretation of genomic data with updated gene panels modestly improved diagnostic yield at minimal cost. However, to justify the additional costs of genome vs exome sequencing, efficient methods for analysis of structural variation will be required and / or cost of genome analysis and storage will need to decrease., (© 2022. The Author(s).)

Purpose: Stroke can cause physical and emotional problems affecting sexual well-being; healthcare professionals (HCPs) are often uncomfortable discussing this topic with patients. We explored the perspectives of HCPs and stroke survivors about barriers to discussing sexual well-being poststroke., Design: A mixed methodology was employed., Methods: A postal survey of stroke survivors (n = 50), a focus group with HCPs on a stroke unit (n = 6), and a focus group with community-living stroke survivors (n = 6) were used in this study. Focus group data were analyzed thematically., Findings: No patient surveyed (60% response rate) had discussed sexual well-being with an HCP. Focus groups revealed barriers on multiple levels: structural, HCP, patient, and professional-patient interface., Conclusions: Healthcare professionals were poorly trained, adopted a passive role, and addressed sexual activity based on individual beliefs rather than having an agreed team approach., Clinical Relevance: Relatively simple steps like inclusion in policy, training to empower HCPs, and the provision of written information for patients could help to improve practice.

Background: screening for cognitive impairment in Emergency Department (ED) requires short, reliable tools., Objective: to validate the 4AT and 6-Item Cognitive Impairment Test (6-CIT) for ED dementia and delirium screening., Design: diagnostic accuracy study., Setting/subjects: attendees aged ≥70 years in a tertiary care hospital's ED., Methods: trained researchers assessed participants using the Standardised Mini Mental State Examination, Delirium Rating Scale-Revised 98 and Informant Questionnaire on Cognitive Decline in the Elderly, informing ultimate expert diagnosis using Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for dementia and delirium (reference standards). Another researcher blindly screened each participant, within 3 h, using index tests 4AT and 6-CIT., Result: of 419 participants (median age 77 years), 15.2% had delirium and 21.5% had dementia. For delirium detection, 4AT had positive predictive value (PPV) 0.68 (95% confidence intervals: 0.58-0.79) and negative predictive value (NPV) 0.99 (0.97-1.00). At a pre-specified 9/10 cut-off (9 is normal), 6-CIT had PPV 0.35 (0.27-0.44) and NPV 0.98 (0.95-0.99). Importantly, 52% of participants had no family present. A novel algorithm for scoring 4AT item 4 where collateral history is unavailable (score 4 if items 2-3 score ≥1; score 0 if items 1-3 score is 0) proved reliable; PPV 0.65 (0.54-0.76) and NPV 0.99 (0.97-1.00). For dementia detection, 4AT had PPV 0.39 (0.32-0.46) and NPV 0.94 (0.89-0.96); 6-CIT had PPV 0.46 (0.37-0.55) and NPV 0.94 (0.90-0.97)., Conclusion: 6-CIT and 4AT accurately exclude delirium and dementia in older ED attendees. 6-CIT does not require collateral history but has lower PPV for delirium., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: A large proportion of older adults with dementia remain undiagnosed, presenting to hospital with occult dementia, and are at risk for adverse outcomes, especially delirium. Routine screening for cognitive impairment among older adult patients presenting to acute hospitals could help alleviate this problem; however, this is hampered by time constraints, poor knowledge of screening instruments and lack of consensus as to which screening tool is best. Cognitive tests with attention items may be particularly useful in acute settings, given the importance of delirium detection. However, it is crucial that cognitive screening instruments are fast and reliable., Summary: The Six-Item Cognitive Impairment Test (6-CIT) is a feasible instrument for cognitive screening among older adults attending a general practitioner or hospital. Although researchers have investigated its accuracy in diagnosing cognitive impairment in primary and secondary care settings, its validity in primary care use has been questioned and there are limited validation studies on its use in secondary care., Key Messages: This paper presents a review of validation studies conducted on the 6-CIT. We recommend that larger studies, which test the psychometric properties of the 6-CIT in primary and acute care settings, are conducted to establish recommendations for routine screening use., (© 2016 S. Karger AG, Basel.)

Aim: To determine whether the provision of an information booklet on mobilisation improves early mobility postsurgical repair of hip fracture., Background: Hip fracture among older people can have long-lasting consequences with the majority of patients failing to achieve their prefracture functional status. Early postoperative mobility may have a positive effect on long-term recovery. The importance of providing postoperative information on mobility has been highlighted. It is suggested that patients remain passive in their recovery when they do not understand the importance of mobilisation., Design: The study used a pretest-post-test design of two treatments and a usual care control group., Methods: Eighty-three adults postsurgical repair of hip fracture, aged 65 years and older, were recruited to the study. Participants were assigned to one of three groups, a usual care group, treatment group 1 (T(1)) usual care plus basic information booklet or treatment group 2 (T(2)) usual care plus detailed information booklet. Data collection three days postsurgery and prior to discharge included the Mini-Mental State Examination, a Demographic Questionnaire, the Elderly Mobility Scale and a Numerical Pain Scale., Results: Greatest improvements in Elderly Mobility Scale scores occurred in T(1), with least changes observed in T(2). Changes did not reach significance level (p=0·105)., Conclusion: The results of the study suggest that the provision of basic information is preferable and highlights a deficiency of education in usual care., Relevance to Clinical Practice: Hip fracture patients should be provided with an educational booklet containing basic information on mobility to promote optimal recovery., (© 2011 Blackwell Publishing Ltd.)

End stage renal disease and renal replacement therapies predispose individuals to a multitude of unwanted symptoms. Fatigue is one of the most frequently reported and disruptive symptoms experienced by patients with ESRD. Living with fatigue places added burdens on individuals and can impact negatively on quality of life. Nephrology nurses must ensure that patients'fatigue is managed effectively. Researching interventions to reduce fatigue among patients with ESRD should therefore become a priority. This article provides a review of research on the symptom of fatigue in individuals living with ESRD.

Aim: To measure fatigue and physical functioning in patients with end stage renal disease (ESRD) receiving haemodialysis and to investigate the relationships between fatigue and physical functioning., Background: Fatigue and reduced physical functioning are among the most bothersome symptoms experienced by individuals receiving haemodialysis for ESRD. Research has shown that increasing activity levels has resulted in decreased fatigue levels and improved physical functioning in individuals with cancer. Establishing whether or not a relationship exists between both concepts in haemodialysis patients is a preliminary step in identifying potential fatigue reducing strategies necessary for improved wellbeing., Method: A quantitative exploratory correlational design was used with 46 individuals completing the Multi-dimensional Fatigue Inventory, the Medical Outcomes Study Short-Form 36-item questionnaire and a Demographic Questionnaire., Results: Results indicated fatigue was prevalent with highest scores achieved for physical fatigue; reduced activity and general fatigue. Substantial limitations in physical functioning were found. A significant moderate negative relationship between general fatigue and physical functioning indicated that, as physical functioning levels increased, fatigue levels decreased. A significant difference was also found between general fatigue scores for males and females. Significant relationships were found between overall physical functioning, older age and employment status., Conclusion: The research indicates the prevalence of fatigue and limitations in physical functioning in individuals with ESRD. However, as physical functioning increased fatigue decreased; a finding relevant to clinical nursing., Relevance to Clinical Practice: Understanding the levels of fatigue and the value of exercise is of relevance to clinical practice thus assessment of fatigue and physical functioning ability in the clinical setting is necessary.

This review presents an analysis of research published by Irish nurses during the period 1990-2005. The analysis is the first effort made to identify the main characteristics of Irish nursing research. Overall, 213 published studies were identified for consideration, from which, 152 were included in the review. The studies were published in 60 journals, 4 books, and 8 research reports. Journal articles selected from 6 journals accounted for 52%. Inclusion criteria were quality of research design, sampling (including sample size), data analysis, scientific merit, and authorship. Each article was analyzed based on this schema. The major areas of research identified included clinical practice (56%) (e.g., medical surgical, mental health, intellectual disability, and maternal and child), nursing management and professional issues (19%), and nursing education (25%).