United Kingdom Cohort Research Articles

Generating synthetic identifiers to support development and evaluation of data linkage methods

We aimed to develop a framework for generating synthetic identifier datasets to support development and evaluation of data linkage methods. We evaluated whether replicating associations between attributes and identifiers improved the utility of the synthetic data for assessing linkage error. We determined the steps required to generate synthetic identifiers that replicate the properties of real-world data collection. We generated synthetic versions of a large United Kingdom cohort study (the Avon Longitudinal Study of Parents and Children), according to the quality and completeness of identifiers recorded over several waves of the cohort. We evaluated the utility of the synthetic identifier data in terms of assessing linkage quality (false matches and missed matches). Comparing data from two collection points in ALSPAC, we found within-person disagreement in identifiers (differences in recording due to both natural change and non-valid entries) in 18% of surnames and 12% of forenames. Rates of disagreement varied by maternal age and ethnic group. Synthetic data provided accurate estimates of linkage quality metrics compared with the original data (within 0.13-0.55% for missed matches and 0.00-0.04% for false matches). Incorporating associations between identifier errors and maternal age/ethnicity improved synthetic data utility. Replicating dependencies between attribute values (e.g. ethnicity), values of identifiers (e.g. name), identifier disagreements (e.g. missing values, errors or changes over time), and their patterns and distribution structure enables generation of realistic synthetic data that can be used for robust evaluation of linkage methods. Our framework provides a novel and generalisable mechanism for developing and benchmarking record linkage algorithms.

Unveiling unique clinical phenotypes of hip fracture patients and the temporal association with cardiovascular events

Cardiovascular events are the leading cause of death among hip fracture patients. This study aims to identify subphenotypes of hip fracture patients and investigate their association with incident cardiovascular events, all-cause mortality, and health service utilisation in Hong Kong and the United Kingdom populations. By the latent class analysis, we show three distinct clusters in the Hong Kong cohort (n = 78,417): Cluster 1 has cerebrovascular and hypertensive diseases, hyperlipidemia, and diabetes; Cluster 2 has congestive heart failure; Cluster 3 consists of relatively healthy patients. Compared to Cluster 3, higher risks of major adverse cardiovascular events are observed in Cluster 1 (hazard ratio 1.97, 95% CI 1.83 to 2.12) and Cluster 2 (hazard ratio 4.06, 95% CI 3.78 to 4.35). Clusters 1 and 2 are also associated with a higher risk of mortality, more unplanned accident and emergency visits and longer hospital stays. Self-controlled case series analysis shows a significantly elevated risk of major adverse cardiovascular events within 60 days post-hip fracture. Similar associations are observed in the United Kingdom cohort (n = 27,948). Pre-existing heart failure is identified as a unique subphenotype associated with poor prognosis after hip fractures.

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

Deep Learning-based Segmentation of Computed Tomography Scans Predicts Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

Rationale: Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. Objectives: To develop automated imaging biomarkers using deep learning-based segmentation of CT scans. Methods: We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort. The relationships among CT biomarkers, lung function, disease progression, and mortality were assessed. Measurements and Main Results: Data from 446 PROFILE patients were analyzed. Median follow-up duration was 39.1 months (interquartile range, 18.1-66.4 mo), with a cumulative incidence of death of 277 (62.1%) over 5 years. Segmentation was successful on 97.8% of all scans, across multiple imaging vendors, at slice thicknesses of 0.5-5 mm. Of four segmentations, lung volume showed the strongest correlation with FVC (r = 0.82; P < 0.001). Lung, vascular, and fibrosis volumes were consistently associated across cohorts with differential 5-year survival, which persisted after adjustment for baseline gender, age, and physiology score. Lower lung volume (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.96-0.99]; P = 0.001), increased vascular volume (HR, 1.30 [95% CI, 1.12-1.51]; P = 0.001), and increased fibrosis volume (HR, 1.17 [95% CI, 1.12-1.22]; P < 0.001) were associated with reduced 2-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR, 3.41 [95% CI, 1.36-8.54]; P = 0.009) and increasing fibrosis volume (HR, 2.23 [95% CI, 1.22-4.08]; P = 0.009) were associated with differential survival. Conclusions: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints.

Identifying critically ill children in Malawi: A modified qSOFA score for low-resource settings.

In low-resource settings, a reliable bedside score for timely identification of children at risk of dying, could help focus resources and improve survival. The rapid bedside Liverpool quick Sequential Organ Failure Assessment (LqSOFA) uses clinical parameters only and performed well in United Kingdom cohorts. A similarly quick clinical assessment-only score has however not yet been developed for paediatric populations in sub-Saharan Africa. In a development cohort of critically ill children in Malawi, we calculated the LqSOFA scores using age-adjusted heart rate and respiratory rate, capillary refill time and Blantyre Coma Scale, and evaluated its prognostic performance for mortality. An improved score, the Blantyre qSOFA (BqSOFA), was developed (omitting heart rate, adjusting respiratory rate cut-off values and adding pallor), subsequently validated in a second cohort of Malawian children, and compared with an existing score (FEAST-PET). Prognostic performance for mortality was evaluated using area under the receiver operating characteristic curve (AUC). Mortality was 15.4% in the development (N = 493) and 22.0% in the validation cohort (N = 377). In the development cohort, discriminative ability (AUC) of the LqSOFA to predict mortality was 0.68 (95%-CI: 0.60-0.76). The BqSOFA and FEAST-PET yielded AUCs of 0.84 (95%-CI:0.79-0.89) and 0.83 (95%-CI:0.77-0.89) in the development cohort, and 0.74 (95%-CI:0.68-0.79) and 0.76 (95%-CI:0.70-0.82) in the validation cohort, respectively. We developed a simple prognostic score for Malawian children based on four clinical parameters which performed as well as a more complex score. The BqSOFA might be used to promptly identify critically ill children at risk of dying and prioritize hospital care in low-resource settings.

Do child mental &amp; physical health explain inequalities in adolescent NEET status? A UK Cohort Study

Abstract Around 1 in 10 young people (YP) (16-24 years) are Not in Education, Employment, or Training (NEET) in the United Kingdom (UK). Socioeconomically disadvantaged YP are more likely to become NEET. Poor physical and mental health and disability are known risk factors for NEET status, yet their potential to mediate the relationship between socioeconomic circumstances (SEC) and NEET status remains unclear. We aimed to quantify which childhood health pathways explain inequalities in adolescent NEET status. We analysed data on 5,786 YP from the Millennium Cohort Study (MCS), a nationally representative sample of the UK population. Early life SEC was measured by highest parental occupational status at birth. NEET status was derived from four questions on education, employment, and training at 17 years. Mediators across childhood were grouped into family health (parental limiting illness, mental and general health, and young carer status) perinatal health (birth weight, smoking during pregnancy, school readiness score), physical health (weight status, asthma, general health, longstanding illness at 11 years), and mental health (mental health score, self-esteem, and ASD/ADHA statement). We used logistic regression to examine the total effect of SEC on adolescent NEET status whilst adjusting for confounders (sex, maternal age, and education), then adjusted for potential mediators. Using causal mediation analysis, we will estimate the proportion mediated by blocks of mediators and the natural indirect effect (NIE) via each block of mediators. After adjustment for confounding, YP whose parents were unemployed were more than 8 times as likely to be NEET at 17 years compared with those whose parents had managerial occupations (Odds Ratio (OR) 8.55, 95% CI 3.73 to 19.64). After adjustment for all childhood health conditions, there was a 34% reduction to aOR 5.99 (95% CI 2.42 to 14.85). Childhood health conditions partially contribute to inequalities in adolescent NEET status. Key messages • Childhood mental and physical health are important for targeting interventions to reduce inequalities in adolescent NEET status. • More than a third of the social inequality in NEET status was explained by perinatal, physical, and mental health during childhood.

Conceptualising compulsivity through network analysis: A two-sample study

Compulsivity is a transdiagnostic construct crucial to understanding multiple psychiatric conditions and problematic repetitive behaviours. Despite being identified as a clinical- and research-relevant construct, there are limited insights into the internal conceptual structure of compulsivity. To provide a more nuanced understanding of compulsivity, the current study estimated the structure of compulsivity (indexed using the previously validated Cambridge-Chicago Compulsivity Trait Scale, CHI-T) among two large-scale and geographically distinct samples using the network estimation method. The samples consisted of a United Kingdom cohort (n = 122,346, 51.4% female, Mean age = 43.7, SD = 16.5, range = 9–86 years) and a South Africa cohort (n = 2674, 65.6% female, Mean age = 24.6, SD = 8.6, range = 18–65 years). Network community analysis demonstrated that compulsivity was constituted of three interrelated dimensions, namely: perfectionism, cognitive rigidity and reward drive. Further, ‘Completion leads to soothing’ and ‘Difficulty moving from task to task’ were identified as core (central nodes) to compulsivity. The dimensional structure and central nodes of compulsivity networks were consistent across the two samples. These findings facilitate the conceptualisation and measurement of compulsivity and may contribute to the early detection and treatment of compulsivity-related disorders.

The Hidden Economic Consequences of Migraine to the UK Government: Burden-of-Disease Analysis Using a Fiscal Framework.

Background: Migraine is a highly prevalent and incapacitating neurological disorder associated with the highest global disability burden in people aged 15 to 49 years. Europe has the fourth-highest prevalence of migraine, after North America, South America, and Central America, and above Asia and Africa. Migraine leads to relatively modest direct healthcare expenditure but has substantial indirect costs due to reduced productivity. Methods: The economic burden of migraine was estimated in comparison with the general population of the United Kingdom (UK) using an analytical fiscal modeling framework applying the government cost perspective. Published measures of migraine's impact on labor participation were applied to rates of economic activity/inactivity of the general population. The model estimates lifetime changes to earnings from employment, direct and indirect taxes paid, and financial support requirements over the life course. Incremental differences between those affected and unaffected by migraine are reported as net fiscal consequences to public accounts. Fiscal costs are reported as the discounted average per capita over a 20-year time horizon and for the entire annual UK cohort with prevalent migraine. Results: People affected by migraine are more likely to be absent from work, unemployed, and disabled, and to retire early. A 44-year-old individual affected by migraine was associated with £19 823 in excess fiscal costs to the UK government, £1379 per year living with the condition, compared with someone not affected by the disease. Annually, migraine was estimated to represent £12.20 billion to the public economy, approximately £130.63 per migraine episode. The model predicted annual productivity losses in the health and social care workforce to be £2.05 billion and total annual productivity losses to be over £5.81 billion. Conclusions: This fiscal analysis monetizes the occupational consequences of migraine to the UK government, both in terms of lost tax revenue and transfer payments. The findings are substantial and useful to characterize disease severity and to inform the body of evidence considered by decision makers appraising the cost-effectiveness of health technologies.

The Hidden Economic Consequences of Migraine to the UK Government: Burden-of-Disease Analysis Using a Fiscal Framework

Background: Migraine is a highly prevalent and incapacitating neurological disorder associated with the highest global disability burden in people aged 15 to 49 years. Europe has the fourth-highest prevalence of migraine, after North America, South America, and Central America, and above Asia and Africa. Migraine leads to relatively modest direct healthcare expenditure but has substantial indirect costs due to reduced productivity. Methods: The economic burden of migraine was estimated in comparison with the general population of the United Kingdom (UK) using an analytical fiscal modeling framework applying the government cost perspective. Published measures of migraine’s impact on labor participation were applied to rates of economic activity/inactivity of the general population. The model estimates lifetime changes to earnings from employment, direct and indirect taxes paid, and financial support requirements over the life course. Incremental differences between those affected and unaffected by migraine are reported as net fiscal consequences to public accounts. Fiscal costs are reported as the discounted average per capita over a 20-year time horizon and for the entire annual UK cohort with prevalent migraine. Results: People affected by migraine are more likely to be absent from work, unemployed, and disabled, and to retire early. A 44-year-old individual affected by migraine was associated with £19 823 in excess fiscal costs to the UK government, £1379 per year living with the condition, compared with someone not affected by the disease. Annually, migraine was estimated to represent £12.20 billion to the public economy, approximately £130.63 per migraine episode. The model predicted annual productivity losses in the health and social care workforce to be £2.05 billion and total annual productivity losses to be over £5.81 billion. Conclusions: This fiscal analysis monetizes the occupational consequences of migraine to the UK government, both in terms of lost tax revenue and transfer payments. The findings are substantial and useful to characterize disease severity and to inform the body of evidence considered by decision makers appraising the cost-effectiveness of health technologies.

Obesity Burden and Impact of Weight Loss in Saudi Arabia: A Modelling Study.

Obesity and its complications are associated with morbidity, mortality and high economic cost in Saudi Arabia. Estimating this impact at the population level and potential benefits to be gained from obesity reduction is vital to underpin policy initiatives to prevent disease risks. We combined data in an adapted version of the value of weight loss simulation model, to predict reductions in complication rates and cost savings achievable with 15% weight loss in Saudi Arabia over 10years. To obtain model inputs, we conducted a systematic literature review(SLR) to identify data on the prevalence of obesity and its complications in Saudi Arabia, and surveyed specialist physicians and hospital administrators in public (governmental) and private healthcare sectors. We used combinations of age, sex, obesity and type 2 diabetes (T2D) rates in Saudi Arabia to sample a UnitedKingdom (UK) cohort, creating a synthetic Saudi Arabia cohort expected to be representative of the population. The synthetic Saudi Arabia cohort reflected expected comorbidity prevalences in the population, with a higher estimated prevalence of T2D, hypertension and dyslipidaemia than the UK cohort in all age groups. For 100,000 people with body mass index 30-50kg/m2, it was estimated that 15% weight loss would lead to a 53.9% reduction in obstructive sleep apnoea, a 37.4% reduction in T2D and an 18.8% reduction in asthma. Estimated overall cost savings amounted to 1.026 billion Saudi Arabian Riyals; the largest contributors were reductions in T2D (30% of total cost savings for year 10), dyslipidaemia (26%) and hypertension (19%). Sustained weight loss could significantly alleviate the burden of obesity-related complications in Saudi Arabia. Adopting obesity reduction as a major policy aim, and ensuring access to support and treatment should form an important part of the transformation of the healthcare system, as set out under 'Vision 2030'.

Editor's Choice Articles for December.

Editor's Choice Articles for December.

Mid-Regional Pro-Adrenomedullin in Combination With Pediatric Early Warning Scores for Risk Stratification of Febrile Children Presenting to the Emergency Department: Secondary Analysis of a Nonprespecified United Kingdom Cohort Study.

Current sepsis guidelines do not provide good risk stratification of subgroups in whom prompt IV antibiotics and fluid resuscitation might of benefit. We evaluated the utility of mid-regional pro-adrenomedullin (MR-proADM) in identification of patient subgroups at risk of requiring PICU or high-dependency unit (HDU) admission or fluid resuscitation. Secondary, nonprespecified analysis of prospectively collected dataset. Pediatric Emergency Department in a United Kingdom tertiary center. Children less than 16 years old presenting with fever and clinical indication for venous blood sampling ( n = 1,183). None. Primary outcome measures were PICU/HDU admission or administration of fluid resuscitation, with a secondary outcome of definite or probable bacterial infection. Biomarkers were measured on stored plasma samples and children phenotyped into bacterial and viral groups using a previously published algorithm. Of the 1,183 cases, 146 children (12.3%) required fluids, 48 (4.1%) were admitted to the PICU/HDU, and 244 (20.6%) had definite or probable bacterial infection. Area under the receiver operating characteristic (AUC) was used to assess performance. MR-proADM better predicted fluid resuscitation (AUC, 0.73; 95% CI, 0.67-0.78), than both procalcitonin (AUC, 0.65; 95% CI, 0.59-0.71) and Pediatric Early Warning Score (PEWS: AUC, 0.62; 95% CI, 0.56-0.67). PEWS alone showed good accuracy for PICU/HDU admission 0.83 (0.78-0.89). Patient subgroups with high MR-proADM (≥ 0.7 nmol/L) and high procalcitonin (≥ 0.5 ng/mL) had increased association with PICU/HDU admission, fluid resuscitation, and bacterial infection compared with subgroups with low MR-proADM (< 0.7 nmol/L). For children with procalcitonin less than 0.5 ng/mL, high MR-proADM improved stratification for fluid resuscitation only. High MR-proADM and high procalcitonin were associated with increased likelihood of subsequent disease progression. Incorporating MR-proADM into clinical risk stratification may be useful in clinician decision-making regarding initiation of IV antibiotics, fluid resuscitation, and escalation to PICU/HDU admission.

The causal association of polyunsaturated fatty acids with allergic disease: A two-sample Mendelian randomization study.

ObjectivesPrevious studies have reported a potential association of polyunsaturated fatty acids (PUFAs) levels with allergic disease risk and the possible benefit of PUFAs supplementation on allergic disease prevention. This study was performed to estimate the genetic association between PUFAs and allergic diseases using the method of both univariable and multivariable two-sample Mendelian randomization (MR).MethodsAs indicators of the PUFAs levels, we included the omega-3, omega-6, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), linoleic acid (LA), and the ratio of omega-6 to omega-3 (omega-6:3). Summarized statistics of genome-wide association studies (GWASs) for these PUFAs were obtained from the United Kingdom Biobank and the Twins United Kingdom cohort. Genetic data relating to allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), allergic urticaria (AU) and asthma, were accessed from the FinnGen biobank analysis. Odds ratios and 95% CIs were used to express the impact.ResultsThe MR results denoted a genetic association between the genetically determined increase in omega-3 levels and the decreased risk of some allergic diseases including AD (OR: 0.863; 95% CI: 0.785 to 0.949; p = 3.86E-03), AC (OR:0.720; 95% CI: 0.547 to 0.947; p = 1.87E-02) and AU (OR:0.821; 95% CI: 0.684 to 0.985; p = 3.42E-02), while omega-6 and DHA level was only found to have negatively correlation with risk of AC with ORs of 0.655 (95% CI: 0.445 to 0.964; p = 3.18E-02) and 0.671 (95% CI 0.490 to 0.918; p = 1.25E-02), respectively. Omega-6:3 were causally significantly associated with the increased risk of AD (OR:1.171; 95% CI: 1.045 to 1.312; p = 6.46E-03) and AC (IVW: OR:1.341; 95% CI: 1.032 to 1.743; p = 2.83E-02). After adjustment of age, economic level, BMI, smoking and alcohol behaviors in the multivariable MR analysis, a direct causal protective effect of omega-3 on AD and AC, as well as a direct causal association between DHA and AD were observed. Omega-6:3 was also found to be directly associated with an increased risk of AD and AC. No association was found of EPA or LA with allergic diseases.ConclusionHigher PUFA concentrations (omega-3, omega-6, DHA) and lower omega-6:3 ratios were genetically associated with a lower risk of some allergic diseases.

The Oxford Cognitive Screen for use with Australian people after stroke (OCS-AU): The adaptation process and determining cut scores for cognitive impairment using a cross-sectional normative study.

Two parallel versions (A and B) of the Oxford Cognitive Screen (OCS) were developed in the United Kingdom (UK) as a stroke-specific screen of five key cognitive domains commonly affected post-stroke. We aimed to develop the Australian versions A and B (OCS-AU), including Australian cut-scores indicative of impairment. We hypothesised there to be no difference in performance between the UK and Australian normative data cohorts. Our multidisciplinary expert panel used the UK pre-defined process to develop the OCS-AU versions A and B. We then conducted a cross-sectional normative study. We purposively recruited community-dwelling, Australian-born, and educated adults; with no known cognitive impairment; representative of age, sex, education level, and living location; at seven sites (four metropolitan, three regional) across four Australian states. Participants completed one or both OCS-AU versions in a randomised order. Australian cohorts were compared with the corresponding UK cohorts for demographics using Pearson's chi-squared test for sex and education, and Welch two-sample t test for age. For the cut-scores indicating cognitive impairment, the fifth (95th) percentiles and group mean performance score for each scored item were compared using Welch two-sample t tests. The pre-defined criteria for retaining OCS cut-scores had no statistically significant difference in either percentile or group mean scores for each scored item. Participants (n= 83) were recruited: fifty-eight completed version A [age (years) mean = 61,SD = 15; 62% female], 60 completed version B [age (years) mean = 62,SD = 13, 53% female], and 35 completed both [age (years) mean = 64,SD = 11, 54% female]. Education was different between the cohorts for version B (12 years, p= 0.002). Cut-scores for all 16 scored items for the OCS-AU version B and 15/16 for version A met our pre-defined criteria for retaining the OCS cut scores. The OCS-AU provides clinicians with an Australian-specific, first-line cognitive screening tool for people after stroke. Early screening can guide treatment and management.

The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts

Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and2009. Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). Corneal-compensated IOP. Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06-0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08-0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05-0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07-0.31 mmHg; P= 0.001), 0.14 mmHg (95% CI, 0.03-0.25 mmHg; P= 0.016), and 0.17 mmHg (95% CI, 0.06-0.29 mmHg; P= 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95% CI, -0.08 to -0.03; P<0.001) was not replicated in the EPIC-Norfolk cohort (P= 0.30). Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

Synonymous mutation in adenosine triphosphatase copper-transporting beta causes enhanced exon skipping in Wilson disease.

Wilson disease (WD) is caused by biallelic pathogenic variants in adenosine triphosphatase copper‐transporting beta (ATP7B); however, genetic testing identifies only one or no pathogenic ATP7B variant in a number of patients with WD. Synonymous single‐nucleotide sequence variants have been recognized as pathogenic in individual families. The aim of the present study was to evaluate the prevalence and disease mechanism of the synonymous variant c.2292C>T (p.Phe764=) in WD. A cohort of 280 patients with WD heterozygous for a single ATP7B variant was investigated for the presence of c.2292C>T (p.Phe764=). In this cohort of otherwise genetically unexplained WD, the allele frequency of c.2292C>T (p.Phe764=) was 2.5% (14 of 560) compared to 7.1 × 10−6 in the general population (2 of 280,964 in the Genome Aggregation Database; p < 10−5; Fisher exact test). In an independent United Kingdom (UK) cohort, 2 patients with WD homozygous for p.Phe764= were identified. RNA analysis of ATP7B transcripts from patients homozygous or heterozygous for c.2292C>T and control fibroblasts showed that this variant caused high expression of an ATP7B transcript variant lacking exon 8. Conclusion: The synonymous ATP7B variant c.2292C>T (p.Phe764=) causes abnormal messenger RNA processing of ATP7B transcripts and is associated with WD in compound heterozygotes and homozygotes.

Length of hospital stay following hip fracture and risk of 30 and 90 day mortality in a United Kingdom cohort.

A recent study identified a length of stay (LOS) of 10 days or less following hip fracture is associated with increased risk of 30-day mortality. This effect has not been previously studied for 90-day mortality or in the United Kingdom (UK). Our aim was to investigate the effect of LOS on 30-day and 90-day mortality following hip fracture in a UK population. In this single-centre study, we retrospectively identified consecutive patients with a hip fracture from the National Hip Fracture Database over 3 years. We excluded patients who died as inpatient during their index admission. The main end-points were 30-day and 90-day mortalities and risk factors for these were examined using stepwise univariate and multivariate Cox regression analyses. Of 1228 patients, mortality at 30-days was 1.2% (15 patients) and 7.8% (96 patients) at 90-days. Mean LOS was 24 days and a total of 206 patients had a LOS of 10 days or less. Following cariate analysis, the highest risk factor for 30-day mortality was a LOS of 10 days or less with a hazard ratio of 7.26 (95% confidence interval 2.56-20.51). Other risk factors for 30-day mortality included increasing age, male gender and chest infection. A LOS of 10 days or less was not associated with increased mortality at 90-days. A short LOS was associated with higher risk of early mortality. We recommend that hip fracture patients be fully rehabilitated prior to discharge to reduce the risk of early mortality.

The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study.

Prothrombin induced by vitamin K absence II (PIVKA-II) has recently been validated internationally as a diagnostic biomarker for hepatocellular carcinoma (HCC), as part of the GALAD model. However, its role as a treatment response biomarker has been less well explored. We, therefore, undertook a prospective study at a tertiary centre in the UK to evaluate the role of PIVKA-II as a treatment response biomarker in patients with early, intermediate and advanced stage HCC. In a cohort of 141 patients, we found that PIVKA-II levels tracked concordantly with treatment response in the majority of patients, across a range of different treatment modalities. We also found that rises in PIVKA-II levels almost always predated radiological progression. Among AFP non-secretors, PIVKA-II was found to be informative in 60% of cases. In a small cohort of patients undergoing liver transplantation, pre-transplant PIVKA-II levels predicted for microvascular invasion and poorer differentiation. Our results demonstrate the potential utility of PIVKA-II as a treatment response biomarker and in predicting microvascular invasion, in a Western population. PIVKA-II demonstrated improved performance over AFP but, as a single biomarker, its performance was still limited. Further larger prospective studies are recommended to evaluate PIVKA-II as a treatment response biomarker, within the GALAD model.

Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial

Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial

745P Ovarian Cancer Retrospective European (O’CaRE) observational study to assess burden of disease and time to next treatment in real-world clinical practice: Results from the United Kingdom (UK)

The retrospective O’CaRE study assessed real-world burden of disease, treatment patterns, and outcomes in patients (pts) with ovarian cancer (OC) through analysis of healthcare data across 5 European countries. Interim results are reported herein for the UK cohort.