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Summary: Background: Vitamin D deficiency has been associated with non‐alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown. Objectives: The objectives of this study were to determine in UK children with biopsy‐proven NAFLD (i) their vitamin D status throughout a 12‐month period and (ii) interactions between key vitamin D‐related genetic variants (nicotinamide adenine dinucleotide synthase‐1/dehydrocholesterol reductase‐7, vitamin D receptor, group‐specific component, CYP2R1) and disease severity. Methods: In 103 paediatric patients with NAFLD, serum 25‐hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy and examined in relation to NAFLD activity score and fibrosis stage. Results: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (<25 nmol·L−1, 25.5%) or insufficient (<50 nmol·L−1, 55.3%). Patients had significantly lower 25OHD levels in winter months (95% CI: 22.7–31.2 nmol·L−1) when compared with spring (30.5–42.1 nmol·L−1; P = 0.0089), summer (36.3–47.2 nmol·L−1; P < 0.0001) and autumn (34.2–47.5 nmol·L−1; P = 0.0003). Polymorphisms in the nicotinamide adenine dinucleotide synthase‐1/dehydrocholesterol reductase‐7 (rs3829251, rs12785878) and vitamin D receptor (rs2228570) genes were independently associated with increased steatosis; while a group‐specific component variant (rs4588) was associated with increased inflammation in liver biopsies. Conclusions: Children with NAFLD in the UK have particularly low winter vitamin D status, with vitamin D insufficiency prevalent throughout the year. Polymorphisms in the vitamin D metabolic pathway are associated with histological severity of paediatric NAFLD. [ABSTRACT FROM AUTHOR]

As part of EU incentives, the UK government have set ambitious environmental targets relating to energy consumption including a reduction of carbon emissions of 80% by 2050. The use of various technologies can help meet these targets as well as providing a secure energy source for the UK in the future. This research took the UK as a case study and investigated where reduction measures are most suited to reduce energy consumption. This paper presents a review on the current state-of-the-art on the domestic technology available, in particular solar energy, heat pumps, phase changing materials (PCMs) and micro combined heat and power (micro-CHP) systems, aiming at identifying research and development opportunities for energy saving in these fields. Furthermore, the financial as well as environmental aspects are assessed as these are the two key considerations of typical household. A typical UK house design, including the floor plan, is created through the use of computer aided design (CAD) software. The house design gives a payback period between 8.7 years at best and 11.6 years at worst. [ABSTRACT FROM AUTHOR]

Background/aims: To elicit the preferences and calculate the willingness to pay (WTP) of patients with ocular hypertension (OHT) for eye monitoring services in the UK., Methods: Patients with OHT aged at least 18 years recruited from four NHS ophthalmology departments were included in the study. Patients' preferences and WTP for an OHT monitoring service in the National Health Service were elicited using a discrete choice experiment (DCE) within a postal survey based on six attributes: (1) how OHT monitoring is organised, (2) monitoring frequency, (3) travel time from home, (4) use of a risk calculator for conversion to glaucoma, (5) risk of developing glaucoma in the next 10 years and (6) cost of monitoring. We used a sequential mixed-methods approach to design the survey., Results: 360 patients diagnosed with OHT were recruited with a mean age of 69 years. In the DCE, reducing the risk of conversion to glaucoma was the most important factor influencing respondents' choice of monitoring service. Respondents preferred hospital-based monitoring services to community optometrist monitoring, and annual monitoring compared with more frequent (every 6 months) and less frequent (every 18 or 24 months) monitoring. These results can be monetised using WTP. Results of heterogeneity analysis suggest that patients with prior experience in community optometrist monitoring preferred this to hospital-based monitoring., Conclusions: Although hospital-based monitoring is generally preferred, patients with prior experience in community services have a different opinion, suggesting that patients who are unfamiliar with community optometry services may need additional support to accept monitoring in this setting., Competing Interests: Competing interests: GG: Consulting: Alcon, Allergan, Belkin, Elios, Equinox, Genentech/Roche, Glaukos, Ivantis, McKinsey, Rayner, Reichert, Ripple Therapeutics, Santen, Sight Sciences, Thea, Vialase, Visufarma, Zeiss; Grants: Thea, Santen; Honoraria: Alcon, Allergan, Belkin, Glaukos, Ivantis, Lumibird, McKinsey, Reichert, Sight Sciences, Thea; Travel: Ivantis, Thea; Board membership: Glaucoma UK, UK & Ireland Glaucoma Society. AK: Advisory Board: Thea & Abbvie. DPC: Consulting: Apellis; Financial Support: Apellis, Santen; Recipient: Allergan/Abbvie, Janssen, Santen, Thea. YT: Grants: National Institute of Health Research. VW: Chief Scientist Office, Scotland; National Institute for Health Research; Economic and Social Research Council; Economic and Social Research Council and Global Challenges Research Fund; Imperial College London; The Urology Foundation. RH: Grants: Chief Scientist Office, Scotland; National Institute of Health Research., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background : (Poly)phenol intake has been associated with reduced risk of non-communicable diseases in epidemiological studies. However, there are currently no dietary assessment tools specifically developed to estimate (poly)phenol intake in the UK population. Objectives : This study aimed to develop a novel food frequency questionnaire (FFQ) to capture the dietary (poly)phenol intake in the UK and assess its relative validity with 7 day diet diaries (7DDs) and plasma and urine (poly)phenol metabolites. Methods : The KCL (poly)phenol FFQ (KP-FFQ) was developed based on the existing EPIC (European Prospective Investigation into Diet and Cancer)-Norfolk FFQ, which has been validated for energy and nutrient intake estimation in the UK population. Participants aged 18-29 years ( n = 255) completed both the KP-FFQ and the EPIC-Norfolk FFQ. In a subgroup ( n = 60), 7DD, spot urine, and fasting plasma samples were collected. An in-house (poly)phenol database was used to estimate (poly)phenol intake from FFQs and 7DDs. Plasma and urinary (poly)phenol metabolite levels were analysed using a validated ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry method. The agreements between (poly)phenol intake estimated using the KP-FFQ, EPIC-Norfolk FFQ and 7DDs, as well as plasma and urinary biomarkers, were evaluated by intraclass correlation coefficients (ICC), weighted kappa, quartile cross-classification, and Spearman's correlations, and the associations were investigated using linear regression models adjusting for energy intake and multiple testing (false discovery rate (FDR) < 0.05). Results : The mean (standard deviation, SD) of total (poly)phenol intake estimated from KP-FFQs was 1366.5 (1151.7) mg d -1 . Fair agreements were observed between ten (poly)phenol groups estimated from KP-FFQs and 7DDs (kappa: 0.41-0.73), including total (poly)phenol intake (kappa = 0.45), while the agreements for the rest of the 17 classes and subclasses were poor (kappa: 0.07-0.39). Strong positive associations with KP-FFQ were found in ten (poly)phenols estimated from 7DDs, including dihydroflavonols, theaflavins, thearubigins, flavones, isoflavonoids, ellagitannins, hydroxyphenylacetic acids, total stilbenes, resveratrol, and tyrosols with stdBeta ranged from 0.61 (95% confidence interval CI: 0.42 to 0.81) to 0.95 (95% CI: 0.86 to 1.03) (all FDR adjusted p < 0.05). KP-FFQs estimated (poly)phenol intake exhibited positive associations with 76 urinary metabolites (stdBeta: 0.28 (95% CI: 0.07-0.49) to 0.81 (0.62-1.00)) and 19 plasma metabolites (stdBeta: 0.40 (0.17-0.62)-0.83 (0.64-1.02)) (all FDR p < 0.05). The agreement between KP-FFQs and the EPIC-Norfolk FFQs was moderate (ICC 0.51-0.69) for all (poly)phenol subclasses after adjusting for energy intake. Compared with the EPIC-Norfolk FFQs estimated (poly)phenol intake, stronger and more agreements and associations were found in KP-FFQs estimated (poly)phenol with 7DDs and biomarkers. Conclusion : (Poly)phenol intake estimated from KP-FFQ exhibited fair agreements and moderate to strong associations with 7DDs and biomarkers, indicating the novel questionnaire may be a promising tool to assess dietary (poly)phenol intake.

Background: Metabolic dysfunction-associated fatty liver disease is a significant risk factor for cardiovascular disease (CVD). This study assesses the association between leisure-time physical activity, sedentary behavior, and CVD risk among patients with metabolic dysfunction-associated fatty liver disease, considering genetic predisposition to CVD., Methods: This cohort study included 157 794 participants with metabolic dysfunction-associated fatty liver disease from the UK Biobank who were free of CVD at baseline. The study measured leisure-time sedentary behaviors (watching TV, using a computer, and driving) and physical activities (walking for pleasure, light and heavy do-it-yourself activities, strenuous sports, and other exercises) in terms of frequency and duration over the 4 weeks before assessment. Both a Cox proportional hazard model and an isotemporal substitution model were utilized in the study to assess the association between leisure sedentary behavior, physical activities, and CVD risk., Results: During a median 12.5 years of follow-up, 26 355 CVD cases were reported, including 19 746 coronary heart disease, 4836 stroke, and 7398 heart failure cases. High physical activity levels were linked to a significantly lower risk of CVD (21%), coronary heart disease (20%), stroke (15%), and heart failure (31%). In contrast, individuals with >6.5 h/d of sedentary behavior faced a 16% to 21% higher risk of these conditions compared with those with ≤3.5 h/d. Notably, replacing 30 minutes of inactivity with physical activity reduced CVD risks by 3% to 16%, particularly with strenuous sports. A significant interaction was observed between physical activity, sedentary behavior, and genetic predisposition in relation to stroke risk., Conclusions: Among patients with metabolic dysfunction-associated fatty liver disease, higher leisure-time physical activity levels correlate with reduced CVD risks, while increased sedentary behavior is linked to higher CVD risks. Replacing sedentary time with physical activity consistently shows benefits in reducing CVD outcomes, irrespective of genetic predisposition., Competing Interests: None.

Background/aims: To assess the cost-effectiveness of making treatment decisions for patients with ocular hypertension (OHT) based on a risk prediction (RP) tool in the United Kingdom., Methods: A discrete event simulation model was constructed to compare the cost-effectiveness of an alternative care pathway in which the treatment decision was guided by a validated RP tool in secondary care against decision-making based on the standard care (SC). Individual patient sampling was used. Patients diagnosed with OHT and with an intraocular pressure of 24 mm Hg or over entered the model with a set of predefined individual characteristics related to their risk of conversion to glaucoma. These characteristics were retrieved from electronic medical records (n=5740). Different stages of glaucoma were modelled following conversion to glaucoma., Results: Almost all (99%) patients were treated using the RP strategy, and less than half (47%) of the patients were treated using the SC strategy. The RP strategy produced higher cost but also higher quality-adjusted life years (QALYs) than the SC strategy. The RP strategy was cost-effective compared with the SC strategy in the base-case analysis, with an incremental cost-effectiveness ratio value of £11 522. The RP strategy had a 96% probability of being cost-effective under a £20 000 per QALY threshold., Conclusions: The use of an RP tool for the management of patients with OHT is likely to be cost-effective. However, the generalisability of the result might be limited due to the high-risk nature of this cohort and the specific RP threshold used in the study., Competing Interests: Competing interests: GG – Consulting: Alcon, Allergan, Belkin, Elios, Equinox, Genentech/Roche, Glaukos, Ivantis, McKinsey, Rayner, Reichert, Ripple Therapeutics, Santen, Sight Sciences, Thea, Vialase, Visufarma, Zeiss; Grants: Thea, Santen; Honoraria: Alcon, Allergan, Belkin, Glaukos, Ivantis, Lumibird, McKinsey, Reichert, Sight Sciences, Thea; Travel: Ivantis, Thea; Board membership: Glaucoma UK, UK & Ireland Glaucoma Society. AK – Advisory Board: Thea & Abbvie. DC - Consulting: Apellis; Financial Support: Apellis, Santen; Recipient: Allergan/Abbvie, Janssen, Santen, Thea. YT – Grants: National Institute of Health Research. VW: Chief Scientist Office, Scotland; National Institute for Health Research; Economic and Social Research Council; Economic and Social Research Council and Global Challenges Research Fund; Imperial College London; The Urology Foundation. RH – Grants: National Institute of Health Research., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Glaucoma is a chronic disease of the optic nerve and a leading cause of severe visual loss in the UK. Once patients have been diagnosed, they need regular monitoring at hospital eye services. Recent advances in technology mean patients with glaucoma can now monitor their disease at home. This could be more convenient for patients and potentially reduce costs and increase capacity for the NHS. However, it is uncertain whether self-monitoring would be acceptable or possible for patients with glaucoma., Objectives: The objectives were to: identify which patients are most appropriate for home monitoring; understand views of key stakeholders (patients, clinicians, researchers) on whether home glaucoma monitoring is feasible and acceptable; develop a conceptual framework for the economic evaluation of home glaucoma monitoring; and explore the need for and provide evidence on the design of a future study to evaluate the clinical and cost-effectiveness of digital technologies for home monitoring of glaucoma., Design: In-home Tracking of glaucoma: Reliability, Acceptability, and Cost (I-TRAC) was a multiphase mixed-methods feasibility study with key components informed by theoretical and conceptual frameworks., Setting: Expert glaucoma specialists in the UK recruited through professional glaucoma societies; study site staff and patient participants recruited through three UK hospital eye services (England, Scotland, Northern Ireland); and UK research teams recruited though existing networks., Intervention: Home tonometer that measures intraocular pressure and a tablet computer with a visual function application. Patients were asked to use the technology weekly for 12 weeks., Results: Forty-two patients were recruited. Retention and completion of follow-up procedures was successful, with 95% ( n = 40) completing the 3-month follow-up clinic visits. Adherence to the interventions was generally high [adherence to both devices (i.e. ≥ 80% adherence) was 55%]. Overall, patients and healthcare professionals were cautiously optimistic about the acceptability of digital technologies for home monitoring of patients with glaucoma. While most clinicians were supportive of the potential advantages glaucoma home monitoring could offer, concerns about the technologies (e.g. reliability and potential to miss disease progression) and how they would fit into routine care need to be addressed. Additionally, clarity is required on defining the ideal population for this intervention. Plans for how to evaluate value for money in a future study were also identified. However, the study also highlighted several unknowns relating to core components of a future evaluative study that require addressing before progression to a definitive effectiveness trial., Limitations: The main limitation relates to our sample and its generalisability, for example, the over-representation of educated persons of white ethnicity who were generally experienced with technology and research motivated., Conclusions: The In-home Tracking of glaucoma: Reliability, Acceptability, and Cost study has demonstrated 'cautious optimism' when considering patients' and healthcare professionals' views on the acceptability of digital technologies for home monitoring of patients with glaucoma. However, the study also highlighted several unknowns relating to the research question and design of a future evaluative study that require addressing before progression to a randomised controlled trial., Future Work: Further research is required to determine the appropriate population (i.e. low vs. high risk of progression) and further refine the intervention components and delivery for planning of future evaluation studies., Study Registration: This study is registered as Research Registry #6213., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129248) and is published in full in Health Technology Assessment ; Vol. 28, No. 44. See the NIHR Funding and Awards website for further award information.

Background: While the health benefits of physical activity for general population are well-recognized, the prospective associations of physical activity volume and intensity with mortality among cardiometabolic disease individuals remain unclear., Objective: The objective of this study was to investigate the associations of accelerometer-measured intensity-specific physical activity with mortality risk among population with cardiometabolic disease., Design: Prospective cohort study., Setting: Participants were recruited from the United Kingdom (UK) across 22 assessment centers from 2006 to 2010., Participants: A total of 9524 participants from the UK Biobank (median: 67.00 years, interquartile range: 61.00-70.00 years) were included in final study., Methods: Accelerometer-measured total volume, moderate-to-vigorous and light intensity physical activity collecting from 2013 to 2015 were quantified using a machine learning model. Multivariable restricted cubic splines and Cox proportional hazard models with hazard ratios (HRs) and 95 % confidence intervals (CIs) were employed to examine the associations of interests., Results: During the follow-up period (median: 6.87 years; interquartile range: 6.32-7.39 years), there were 659 (6.92 %) death events with 218 (2.29 %) cardiovascular disease-related deaths and 441 (4.63 %) non-cardiovascular disease-related deaths separately. In the fully adjusted models, compared with participants in the lowest quartiles of total volume, moderate-to-vigorous and light physical activities, the adjusted HRs (95 % CIs) of all-cause mortality for those in the highest quartiles were 0.40 (0.31, 0.52), 0.48 (0.37, 0.61), and 0.56 (0.44, 0.71) while those for cardiovascular diseases-related mortality were 0.35 (0.22, 0.55), 0.52 (0.35, 0.78) and 0.59 (0.39, 0.88), and for non-cardiovascular diseases-related mortality, they were 0.42 (0.30, 0.59), 0.40 (0.29, 0.54) and 0.54 (0.40, 0.73), separately. The optimal moderate-to-vigorous-intensity physical activity level for cardiovascular diseases-related mortality reduction was found to be in the third quartile (17.75-35.33 min/day). Furthermore, the observed inverse associations were mainly non-linear., Conclusions: Promoting physical activity, regardless of intensity, is essential for individuals with cardiometabolic disease to reduce mortality risk. For both all-cause and cardiovascular disease-related and non-cardiovascular disease-related mortality, the observed decrease in risk seems to level off at a moderate level. The current findings deriving from precise device-based physical activity data provide inference for secondary prevention of cardiometabolic disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Importance: Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations., Objective: To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth., Design, Setting, and Participants: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023., Exposures: A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure., Main Outcomes and Measures: Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes., Results: This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA., Conclusions and Relevance: The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

Background: Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections., Methods: The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident., Conclusions: PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required., Funding: This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL)., Competing Interests: RZ, YM, LZ, DL, RJ, HW, ZZ, QY, JL, FL, CD, WS, HC No competing interests declared, (© 2024, Zeng, Ma, Zhang et al.)

Background: Previous observational studies have shown a correlation between leisure sedentary behaviors (LSB) and physical activity (PA) with the incidence of obstructive sleep apnea (OSA). However, the causal associations remain unknown. Therefore, our study used bidirectional two-sample Mendelian randomization (MR) to identify potential causal relationships between LSB/PA and OSA., Methods: We sourced genetic variation data for LSB and PA from the UK Biobank, while data on OSA were collected from the FinnGen study. The primary analysis method employed was the inverse variance weighted (IVW) approach, complemented by the weighted median and MR-Egger methods. For sensitivity analyses, we conducted Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis., Results: IVW analyses showed that genetically predicted leisure television watching (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.09-1.75, p  = 0.007) and computer use (OR = 1.48, 95% CI = 1.15-1.92, p  = 0.002) significantly increased the risk of OSA. Conversely, self-reported vigorous physical activity (VPA) (OR = 0.33, 95% CI = 0.11-0.98, p  = 0.046) may reduce the risk of OSA. No causal effects on OSA risk were observed for driving or self-reported moderate-to-vigorous physical activity. Furthermore, the reverse MR analysis indicated no significant causal relationship between OSA and any LSB/PA phenotype. Sensitivity tests showed no significant heterogeneity or horizontal pleiotropy., Conclusion: This study suggests that leisurely television watching and computer use are risk factors for OSA, while VPA may be a protective factor. Additionally, OSA does not affect PA or LSB levels. We recommend reducing sedentary activities, particularly television watching and computer use, and prioritizing VPA to reduce the risk of OSA. Further research in diverse populations and settings is needed to validate these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Wang, Wu, Zhou, Zhang and Wang.)

Background : The association of dairy product consumption with nonalcoholic fatty liver disease (NAFLD) and cirrhosis remains controversial. This study aimed to prospectively investigate the associations between the consumption of the different types of dairy products, genetic predisposition, and the risks of NAFLD and cirrhosis. Methods : This cohort study included 190 145 participants from the UK Biobank Study. The consumption of the different types of dairy products was assessed based on the Oxford WebQ at baseline and defined as the sum of milk, yogurt, and cheese. NAFLD and cirrhosis were evaluated using hospital inpatient records and death data in the UK Biobank. The weighted genetic risk score (GRS) for NAFLD and cirrhosis was constructed using 5 and 6 single-nucleotide variants (SNVs), respectively. Cox proportional hazards regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between genetic factors and different types of dairy products with the incidence of NAFLD and cirrhosis. Results : During a median follow-up of 11.6 years, 1512 NAFLD and 556 cirrhosis cases were ascertained. After adjusting for several potential confounders, the HRs (95% CIs) (Q4 vs. Q1) of NAFLD were 0.86 (0.74, 0.995) for total dairy products, 0.96 (0.84, 1.09) for high-fat dairy products, 0.78 (0.67, 0.92) for low-fat dairy products, 0.86 (0.74, 0.99) for unfermented dairy products, and 0.79 (0.68, 0.91) for fermented dairy products. The multivariable-adjusted HRs (95% CIs) (Q4 vs. Q1) of cirrhosis were 0.75 (0.59, 0.96) for total dairy products, 0.97 (0.78, 1.19) for high-fat dairy products, 0.67 (0.51, 0.89) for low-fat dairy products, 0.75 (0.59, 0.96) for unfermented dairy products, and 0.71 (0.56, 0.90) for fermented dairy products. The associations of high-fat dairy products and fermented dairy products with NAFLD and cirrhosis were found to be nonlinear ( P for nonlinear <0.05). No interaction was observed between dairy product consumption and NAFLD or cirrhosis genetic susceptibility. Conclusions : Higher consumption of dairy products, except for high-fat dairy, was correlated with lower risks of NAFLD and cirrhosis, regardless of their differences in genetic susceptibility.

Aims: This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D)., Materials and Methods: In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D., Results: During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HR RA  = 2.06, 95% CI: 1.76-2.41; HR M10  = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HR RA  = 4.46, 95% CI: 3.36-6.42; HR M10  = 3.15, 95% CI: 2.29-4.32; HR L5  = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05)., Conclusion: The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D., (© 2023 John Wiley & Sons Ltd.)

Purpose: This study aimed to investigate the associations between maternal smoking (MS) and education score in adult offspring., Methods: To better understand this link, we performed a two-stage genome-wide by environment interaction studies (GWEIS) of MS and offspring education score in UK Biobank cohort. Specifically, 276 996 subjects from England were enrolled in the discovery study, while 24 355 subjects from Scotland and 14 526 subjects from Wales were enrolled in the replication study. GWEIS were conducted by PLINK 2.0 with MS used as an environmental risk factor., Results: Significant GWEIS associations ( P  < 0.0001) between MS and offspring education score in both the discovery cohort and two replicate cohorts (Scotland population and Wales population) were identified. GWEIS identified 2 independent significant single nucleotide polymorphism-MS interaction, with one variant located in the chromosomal 16 (rs72768988, Position: 22,768,798, P  = 1.22 × 10 -8 , β = 6.7662) and the other one located in 2q32.3 region (2 : 196424612&#95;GT&#95;G, Position: 196 424 612, 3.60 × 10 -9 , β = -0.4721)., Conclusion: Our results suggested 2q32.3 region and HECW2 gene could negatively moderate the influence of MS on offspring's educational status., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Genetic factors and muscle strength both contribute to the risk of major depressive disorder (MDD), but whether high muscle strength can offset the risk of MDD with different genetic risk is unknown. This study aims to examine whether a higher muscle strength is associated with lower risk of MDD regardless of genetic risk among middle-aged and older adults., Methods: This cohort study obtained data from the UK Biobank, which includes 345,621 individuals aged 40-69 years (mean (standard deviation): 56.7 (7.99) years) without baseline MDD. Polygenic risk score for MDD was categorised as low, intermediate or high. The mean of the right- and left-hand grip strength values was used in the analysis and was divided into three categories., Results: 9,753 individuals developed MDD within 2,752,461 person-years of follow-up. The multivariable adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of MDD across increased grip strength categories were 1.00, 0.72 (0.68-0.75) and 0.56 (0.53-0.59) (P for trend <0.0001). The HRs (95% CIs) of incident MDD across the genetic risk categories were 1.00, 1.11 (1.05-1.17) and 1.20 (1.13-1.28) (P for trend <0.0001); 4.07% of individuals with a high genetic risk and low grip strength developed MDD, and 1.72% of individuals with a low genetic risk and high grip strength developed MDD, with an HR (95% CI) of 0.44 (0.39-0.50)., Conclusions: Both muscle strength and genetic risk were significantly associated with incident MDD. A higher muscle strength was associated with a lower MDD risk among individuals with a high genetic risk. Improving muscle strength should be encouraged for all individuals, including individuals with high genetic risk for MDD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and aims : Onions have shown antidepressant effects but relevant evidence from people was limited. Thus, we aimed to explore the prospective association between onion consumption and risk of depressive symptoms in the general population. Methods : We used data from 2 cohorts: the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort included 7739 participants (males, 57.6%) with a mean age of 39.5 years, and the UK Biobank included 169 806 individuals (males, 45.2%) with a mean age of 55.7 years. In the TCLSIH cohort, onion consumption was assessed by a validated food frequency questionnaire from May 2013; depressive symptoms were evaluated by the Chinese version of the Self-Rating Depression Scale (SDS scores ≥ 45) and were assessed up to 2018. In the UK Biobank, onion consumption was measured by 1-5 times validated 24-hour dietary recalls in 2006-2010; depressive symptoms were determined through the linked hospital records and death registries and were assessed up to 2018. Multivariable Cox proportional hazards models were employed to determine the association between onion consumption and risk of depressive symptoms. Results : A total of 1098 and 1924 cases of depressive symptoms were identified during 15 004 person-years and 1 243 832 person-years of follow-up in the TCLSIH cohort and the UK Biobank, respectively. After adjusting for many confounding factors, the fully adjusted HRs (95% CI) of depressive symptoms comparing the higher levels to the lowest level of onion consumption were 0.78 (0.65, 0.94), 0.73 (0.61, 0.87), and 0.77 (0.64, 0.92) in the TCLSIH cohort ( p for trend = 0.01); and were 0.79 (0.68, 0.93), 0.81 (0.69, 0.94), and 0.97 (0.85, 1.12) in the UK Biobank ( p for trend = 0.07). Similar associations were observed in the sensitivity analyses. Conclusion : Our results indicated that habitual onion consumption was associated with a lower risk of depressive symptoms in two cohorts. However, this association was not statistically significant in the highest level of onion consumption in the UK Biobank.

Introduction: Genetic contributions to hernia development are incompletely understood. This study performed the first comprehensive genome-wide association study (GWAS) for diaphragmatic hernia using a large population-based cohort in the UK Biobank (UKB)., Methods and Procedures: Two-stage GWAS (discovery and confirmation) was performed for diaphragmatic hernia in the UKB. Briefly, 275,549 and 91,850 subjects were randomly selected for association tests in Stages 1 and 2, respectively. Association tests between 8,568,156 SNPs (genotyped or imputed with MAF > 0.01) in the autosomal genome and diaphragmatic hernia were performed in Stage 1. SNPs with P < 1 × 10 -5 were selected for confirmation in Stage 2, and those with P < 0.05 and the same direction of association as Stage 1 were selected for combined association testing; SNPs with combined P < 5 × 10 -8 were considered GWAS-significant. LD clumping analysis identified genetically independent chromosomal regions (loci). A genetic risk score (GRS) measured the cumulative risk of independent SNPs in 91,849 additional subjects using odds ratios (ORs) from Stages 1 and 2., Results: 36,351 patients were identified with diaphragmatic hernia (ICD-10 K44). In Stage 1 analysis, 2654 SNPs were associated (P < 1 × 10 -5 ) with diaphragmatic hernia. Stage 2 analysis confirmed 338 SNPs (P < 0.05). In combined analysis, 245 SNPs reached GWAS significance (P < 5 × 10 -8 ). LD clumping analysis revealed 14 independent loci associated with diaphragmatic hernia. Two loci have been previously associated with inguinal hernia at 2p16 (rs181661155) and 11p13 (rs5030123). eQTL analysis suggested genes CRLF1, UBA52, and CALD1 are also significantly associated with these loci. GRS showed significant increase in cases compared to controls (P < 1 × 10 -16 ) and is associated with increased risk of diaphragmatic hernia (P < 1 × 10 -7 )., Conclusions: We identified 245 SNPs at 14 susceptibility loci associated with diaphragmatic hernia in a large population-based cohort. These results offer insight into pathogenetic mechanisms of diaphragmatic hernia development and may be used in genetic risk scores for pre-operative risk-stratification and clinical prediction models., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Adult height is highly heritable, yet no genetic predictor has demonstrated clinical utility compared to mid-parental height., Objective: To develop a polygenic risk score for adult height and evaluate its clinical utility., Design: A polygenic risk score was constructed based on meta-analysis of genomewide association studies and evaluated on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort., Subjects: Participants included 442 599 genotyped White British individuals in the UK Biobank and 941 genotyped child-parent trios of European ancestry in the ALSPAC cohort., Interventions: None., Main Outcome Measures: Standing height was measured using stadiometer; Standing height 2 SDs below the sex-specific population average was considered as short stature., Results: Combined with sex, a polygenic risk score captured 71.1% of the total variance in adult height in the UK Biobank. In the ALSPAC cohort, the polygenic risk score was able to identify children who developed adulthood short stature with an area under the receiver operating characteristic curve (AUROC) of 0.84, which is close to that of mid-parental height. Combining this polygenic risk score with mid-parental height or only one of the child's parent's height could improve the AUROC to at most 0.90. The polygenic risk score could also substitute mid-parental height in age-specific Khamis-Roche height predictors and achieve an equally strong discriminative power in identifying children with a short stature in adulthood., Conclusions: A polygenic risk score could be considered as an alternative or adjunct to mid-parental height to improve screening for children at risk of developing short stature in adulthood in European ancestry populations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Better phenotyping of routinely collected coded data would be useful for research and health improvement. For example, the precision of coded data for hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) may be as poor as < 50%. This work aimed to investigate the feasibility and added value of automated methods applied to clinical radiology reports to improve stroke subtyping., Methods: From a sub-population of 17,249 Scottish UK Biobank participants, we ascertained those with an incident stroke code in hospital, death record or primary care administrative data by September 2015, and ≥ 1 clinical brain scan report. We used a combination of natural language processing and clinical knowledge inference on brain scan reports to assign a stroke subtype (ischemic vs ICH vs SAH) for each participant and assessed performance by precision and recall at entity and patient levels., Results: Of 225 participants with an incident stroke code, 207 had a relevant brain scan report and were included in this study. Entity level precision and recall ranged from 78 to 100%. Automated methods showed precision and recall at patient level that were very good for ICH (both 89%), good for SAH (both 82%), but, as expected, lower for ischemic stroke (73%, and 64%, respectively), suggesting coded data remains the preferred method for identifying the latter stroke subtype., Conclusions: Our automated method applied to radiology reports provides a feasible, scalable and accurate solution to improve disease subtyping when used in conjunction with administrative coded health data. Future research should validate these findings in a different population setting.

Background: Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlations among medical codes which can potentially be exploited to improve the performance., Methods: To address the issues of model explainability and label correlations, we propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS (National Health Service) COVID-19 (Coronavirus disease 2019) shielding codes. Experiments were conducted to compare the HLAN model and label embedding initialisation to the state-of-the-art neural network based methods, including variants of Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs)., Results: HLAN achieved the best Micro-level AUC and F 1 on the top-50 code prediction, 91.9% and 64.1%, respectively; and comparable results on the NHS COVID-19 shielding code prediction to other models: around 97% Micro-level AUC. More importantly, in the analysis of model explanations, by highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to the CNN-based models and its downgraded baselines, HAN and HA-GRU. Label embedding (LE) initialisation significantly boosted the previous state-of-the-art model, CNN with attention mechanisms, on the full code prediction to 52.5% Micro-level F 1 . The analysis of the layers initialised with label embeddings further explains the effect of this initialisation approach. The source code of the implementation and the results are openly available at https://github.com/acadTags/Explainable-Automated-Medical-Coding., Conclusion: We draw the conclusion from the evaluation results and analyses. First, with hierarchical label-wise attention mechanisms, HLAN can provide better or comparable results for automated coding to the state-of-the-art, CNN-based models. Second, HLAN can provide more comprehensive explanations for each label by highlighting key words and sentences in the discharge summaries, compared to the n-grams in the CNN-based models and the downgraded baselines, HAN and HA-GRU. Third, the performance of deep learning based multi-label classification for automated coding can be consistently boosted by initialising label embeddings that captures the correlations among labels. We further discuss the advantages and drawbacks of the overall method regarding its potential to be deployed to a hospital and suggest areas for future studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning., Materials and Methods: In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness., Results: Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts., Discussion: When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies., Conclusions: Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification., Methods: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models., Results: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites., Conclusions: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.

Objectives: To characterise changes in nationwide fall-related mortality rates in Australia and the United Kingdom (UK) between 2006 and 2016 by age group and sex., Study Design: Trend analysis of falls mortality data from World Health Organization (WHO) Mortality Database for the Australian and UK population., Main Outcome Measures: We assessed age-specific, sex-specific and age-adjusted mortality rates. Mortality trends were assessed via the annual percentage change (APC) using joinpoint regression., Results: The annual average age-adjusted falls mortality rate was 38.63 per 1,000,000 population in Australia, and 34.12 per 1,000,000 population in the UK. From 2006 to 2016, age-adjusted mortality rate due to falls increased in Australia and the UK by an average annual rate of 3.77% (95% CI 2.91% to 4.64%; p<0.01) and 2.11% (95% CI 1.43% to 2.80%; p<0.01) respectively. Death rates from falls increased with age. People aged ≥95 years had the highest mortality rate from falls in Australia and the UK. Men had a higher annual average age-adjusted mortality rate from falls than women (1.6 times higher in Australia and 1.7 times higher in the UK). Women had a larger annual percentage increase in falls mortality rate compared to men over the study period., Conclusions: There was a major increase in reported fall-related deaths in Australia and the UK between 2006 and 2016, especially in the very elderly. Men had a higher mortality rate from falls than women. Factors contributing to the apparent increases in fall-related mortality may include reduced cancer and cardiovascular mortality and better ascertainment of cause of death., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Vitamin D deficiency is highly prevalent across the globe. Existing studies suggest that a low vitamin D level is associated with more than 130 outcomes. Exploring the causal role of vitamin D in health outcomes could support or question vitamin D supplementation., Methods: We carried out a systematic literature review of previous Mendelian-randomization studies on vitamin D. We then implemented a Mendelian Randomization-Phenome Wide Association Study (MR-PheWAS) analysis on data from 339 256 individuals of White British origin from UK Biobank. We first ran a PheWAS analysis to test the associations between a 25(OH)D polygenic risk score and 920 disease outcomes, and then nine phenotypes (i.e. systolic blood pressure, diastolic blood pressure, risk of hypertension, T2D, ischaemic heart disease, body mass index, depression, non-vertebral fracture and all-cause mortality) that met the pre-defined inclusion criteria for further analysis were examined by multiple MR analytical approaches to explore causality., Results: The PheWAS analysis did not identify any health outcome associated with the 25(OH)D polygenic risk score. Although a selection of nine outcomes were reported in previous Mendelian-randomization studies or umbrella reviews to be associated with vitamin D, our MR analysis, with substantial study power (>80% power to detect an association with an odds ratio >1.2 for per standard deviation increase of log-transformed 25[OH]D), was unable to support an interpretation of causal association., Conclusions: We investigated the putative causal effects of vitamin D on multiple health outcomes in a White population. We did not support a causal effect on any of the disease outcomes tested. However, we cannot exclude small causal effects or effects on outcomes that we did not have enough power to explore due to the small number of cases., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: Although the mainstay of colorectal cancer treatment remains operative, a significant proportion of patients end up without surgery. This is because they are either deemed to have no oncological benefit from the resection (too much disease) or to be unfit for major surgery (too frail). The aim of this study was to assess the proportion and survival of these two groups among the totality of practice in a tertiary unit and to discuss the implications on the conceptual understanding of outcome measures., Methods: Data was collected over two study periods with the total duration of four years. Patient demographics, comorbidities, cancer staging and management pathways were all recorded. The primary endpoint was all-cause mortality., Results: The total of 909 patients were examined. In the 29% who did not undergo resectional surgery, 6.5% had too little disease, 13.8% had too much disease, while 8.7% were deemed too frail. The highest two-year mortality was observed in the too much (83.2%) and too frail (75.9%) groups, whereas in patients with too little cancer the rate was 5.1%, and in those undergoing a resection it was 19.2% (P < 0.001)., Conclusions: The study has expectedly shown poor survival in the too much and too frail groups. We believe that understanding the prognosis in these subgroups is vital, as it informs complex decisions on whether to operate. Moreover, an overall reporting taking into account the proportion of these groups in an multidisciplinary team practice (the non-surgical index) is proposed to render individual surgeon's mortality results meaningful as a comparative measure.

Background: Traditional health information systems are generally devised to support clinical data collection at the point of care. However, as the significance of the modern information economy expands in scope and permeates the healthcare domain, there is an increasing urgency for healthcare organisations to offer information systems that address the expectations of clinicians, researchers and the business intelligence community alike. Amongst other emergent requirements, the principal unmet need might be defined as the 3R principle (right data, right place, right time) to address deficiencies in organisational data flow while retaining the strict information governance policies that apply within the UK National Health Service (NHS). Here, we describe our work on creating and deploying a low cost structured and unstructured information retrieval and extraction architecture within King's College Hospital, the management of governance concerns and the associated use cases and cost saving opportunities that such components present., Results: To date, our CogStack architecture has processed over 300 million lines of clinical data, making it available for internal service improvement projects at King's College London. On generated data designed to simulate real world clinical text, our de-identification algorithm achieved up to 94% precision and up to 96% recall., Conclusion: We describe a toolkit which we feel is of huge value to the UK (and beyond) healthcare community. It is the only open source, easily deployable solution designed for the UK healthcare environment, in a landscape populated by expensive proprietary systems. Solutions such as these provide a crucial foundation for the genomic revolution in medicine.

Objective: Unlocking the data contained within both structured and unstructured components of electronic health records (EHRs) has the potential to provide a step change in data available for secondary research use, generation of actionable medical insights, hospital management, and trial recruitment. To achieve this, we implemented SemEHR, an open source semantic search and analytics tool for EHRs., Methods: SemEHR implements a generic information extraction (IE) and retrieval infrastructure by identifying contextualized mentions of a wide range of biomedical concepts within EHRs. Natural language processing annotations are further assembled at the patient level and extended with EHR-specific knowledge to generate a timeline for each patient. The semantic data are serviced via ontology-based search and analytics interfaces., Results: SemEHR has been deployed at a number of UK hospitals, including the Clinical Record Interactive Search, an anonymized replica of the EHR of the UK South London and Maudsley National Health Service Foundation Trust, one of Europe's largest providers of mental health services. In 2 Clinical Record Interactive Search-based studies, SemEHR achieved 93% (hepatitis C) and 99% (HIV) F-measure results in identifying true positive patients. At King's College Hospital in London, as part of the CogStack program (github.com/cogstack), SemEHR is being used to recruit patients into the UK Department of Health 100 000 Genomes Project (genomicsengland.co.uk). The validation study suggests that the tool can validate previously recruited cases and is very fast at searching phenotypes; time for recruitment criteria checking was reduced from days to minutes. Validated on open intensive care EHR data, Medical Information Mart for Intensive Care III, the vital signs extracted by SemEHR can achieve around 97% accuracy., Conclusion: Results from the multiple case studies demonstrate SemEHR's efficiency: weeks or months of work can be done within hours or minutes in some cases. SemEHR provides a more comprehensive view of patients, bringing in more and unexpected insight compared to study-oriented bespoke IE systems. SemEHR is open source, available at https://github.com/CogStack/SemEHR.

Interferon-induced transmembrane 3 (IFITM3) is known to restrict the entry of a range of enveloped viruses. The single nucleotide polymorphism rs12252-C within IFITM3 has been shown to be associated with severe influenza A virus infection. It has been suggested that rs12252-C results in expression of a truncated IFITM3 protein lacking the first 21 amino acids. By performing high-throughput RNA sequencing on primary dendritic cells and peripheral blood mononuclear cells isolated from pandemic H1N1 influenza and human immunodeficiency virus-1 (HIV-1) infected patients we show that full-length IFITM3 mRNA is dominantly expressed (>99%) across all rs12252 genotypes. Full-length IFITM3 protein can be detected in all genotypes., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)