The reduced cost of providing a nationally recognised service for familial hypercholesterolaemia

OBJECTIVE: Familial hypercholesterolaemia (FH) affects 1 in 500 people in the UK population and is associated with premature morbidity and mortality from coronary heart disease. In 2008, National Institute for Health and Care Excellence (NICE) recommended genetic testing of potential FH index cases and cascade testing of their relatives. Commissioners have been slow to respond although there is strong evidence of cost and clinical effectiveness. Our study quantifies the recent reduced cost of providing a FH service using generic atorvastatin and compares NICE costing estimates with three suggested alternative models of care (a specialist-led service, a dual model service where general practitioners (GPs) can access specialist advice, and a GP-led service).METHODS: Revision of existing 3?year costing template provided by NICE for FH services, and prediction of costs for running a programme over 10?years. Costs were modelled for the first population-based FH service in England which covers Southampton, Hampshire, Isle of Wight and Portsmouth (SHIP). Population 1.95 million.RESULTS: With expiry of the Lipitor (Pfizer atorvastatin) patent the cost of providing a 10-year FH service in SHIP reduces by 42.5% (£4.88 million on patent vs £2.80 million off patent). Further cost reductions are possible as a result of the reduced cost of DNA testing, more management in general practice, and lower referral rates to specialists. For instance a dual-care model with GP management of patients supported by specialist advice when required, costs £1.89 million.CONCLUSIONS: The three alternative models of care are now <50% of the cost of the original estimates undertaken by NICE

Liver fibrosis markers and all cause mortality in people with type 2 diabetes:a population based study (The Ayrshire Diabetes Outcomes Cohort (ADOC) Study)

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Nonalcoholic Fatty Liver Disease without overlapping Metabolic Associated Fatty Liver Disease and the risk of incident type 2 diabetes

Background and aims: re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex.Methods: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups.Results: a total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63–3.51) and 5.75 (5.17–6.36) (women), and 1.53 (1.25–1.88) and 2.60 (2.44–2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex &lt;0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes).Conclusions: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.<br/

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults:The Kangbuk Samsung Health Study

Aims: Whether changes in serum uric acid (SUA) are associated with resolution of nonalcoholic fatty liver disease (NAFLD) is uncertain. We aimed to determine the association between (i) baseline SUA and (ii) SUA changes over time, and NAFLD resolution. Materials and Methods: A retrospective cohort study, comprising 38,483 subjects aged &lt;40 years with pre-existing NAFLD, were undertaken. The effects of SUA changes over time were studied in 25,266 subjects. Participants underwent a health examination between 2011 and 2019, and had at least one follow-up liver ultrasound until December 2020. Exposures included baseline SUA levels, and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. Results: During a median follow-up of 4 years, low baseline SUA and decreases in SUA over time, were independently associated with NAFLD resolution (p for trend &lt;0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1 mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, the aHRs (95%CIs) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. Conclusions: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.<br/

Alcohol consumption and metabolic syndrome : Clinical and epidemiological impact on liver disease

Alcohol use and metabolic syndrome are highly prevalent in the population and frequently co-exist. Both are implicated in a large range of health problems, including chronic liver disease, hepatocellular carcinoma, and liver-related outcomes (i.e. decompensation or liver transplantation). Studies have yielded mixed results regarding the effects of mild-moderate alcohol consumption on the risk of metabolic syndrome and fatty liver disease, possibly due to methodological differences. The few available prospective studies have indicated that mild-moderate alcohol use is associated with an increase in liver-related outcomes. This conclusion was substantiated by systems biology analyses suggesting that alcohol and metabolic syndrome may play a similar role in fatty liver disease, potentiating an already existing dysregulation of common vital homeostatic pathways. Alcohol and metabolic factors are independently and jointly associated with liver-related outcomes. Indeed, metabolic syndrome increases the risk of liver-related outcomes, regardless of alcohol intake. Moreover, the components of metabolic syndrome appear to have additive effects when it comes to the risk of liver-related outcomes. A number of population studies have implied that measures of central/abdominal obesity, such as the waist-to-hip ratio, can predict liver-related outcomes more accurately than BMI, including in individuals who consume harmful quantities of alcohol. Many studies even point to synergistic interactions between harmful alcohol use and many metabolic components. This accumulating evidence showing independent, combined, and modifying effects of alcohol and metabolic factors on the onset and progression of chronic liver disease highlights the multifactorial background of liver disease in the population. The available evidence suggests that more holistic approaches could be useful for risk prediction, diagnostics and treatment planning. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

History of gestational diabetes and incident nonalcoholic fatty liver disease:The Kangbuk Samsung Health Study

Objectives: We examined the relationship between a prior history of gestational diabetes mellitus (pGDM) and risk of incident nonalcoholic fatty liver disease (NAFLD) and investigated the effect of insulin resistance or development of diabetes as mediators of any association.Methods: We performed a retrospective cohort study of 64,397 Korean parous women without NAFLD. The presence of, and the severity of NAFLD at baseline and follow-up were assessed using liver ultrasonography. Cox proportional hazards models were used to determine adjusted hazard ratios (aHRs) for incident NAFLD according to a self-reported GDM history, adjusting for confounders as time-dependent variables. Mediation analyses were performed to examine whether diabetes or insulin resistance may mediate the association between pGDM and incident NAFLD. Results: During a median follow-up of 3.7 years, 6,032 women developed incident NAFLD (of whom 343 had moderate-to-severe NAFLD). Multivariable aHRs (95% confidence intervals) comparing women with time-dependent pGDM to the reference group (no pGDM) was 1.46 (1.33–1.59) and 1.75 (1.25–2.44) for incident overall NAFLD and moderate-to-severe NAFLD, respectively. These associations remained significant in analyses restricted to women with normal fasting glucose Conclusions: A prior history of GDM is an independent risk factor for NAFLD development. Insulin resistance, measured by HOMA-IR, and development of diabetes each explained onl

Determining fluid migration and isolation times in multiphase crustal domains using noble gases

Geochemical characteristics in subsurface fluid systems provide a wealth of information about fluid sources, migration, and storage conditions. Determining the extent of fluid interaction (aquifer-hydrocarbon connectivity) is important for oil and gas production and waste storage applications, but is not tractable using traditional seismic methods. Furthermore, the residence time of fluids is critical in such systems and can vary from tens of thousands to billions of years. Our understanding of the transport length scales in multiphase systems, while equally important, is more limited. Noble gas data from the Rotliegend natural gas field, northern Germany, are used here to determine the length scale and isolation age of the combined water-gas system. We show that geologically bound volume estimates (i.e., gas to water volume ratios) match closed-system noble gas model predictions, suggesting that the Rotliegend system has remained isolated as a closed system since hydrocarbon formation. Radiogenic helium data show that fluid isolation occurred 63–129 m.y. after rock and/or groundwater deposition (ca. 300 Ma), which is consistent with known hydrocarbon generation from 250 to 140 Ma, thus corroborating long-term geologic isolation. It is critical that we have the ability to distinguish between fluid systems that, despite phase separation, have remained closed to fluid loss from those that have lost oil or gas phases. These findings are the first to demonstrate that such systems remain isolated and fully gas retentive on time scales >100 m.y. over >10 km length scales, and have broad implications for saline aquifer CO2 disposal site viability and hydrocarbon resource prediction, which both require an understanding of the length and time scales of crustal fluid transport pathways

Human Performance Models of Pilot Behavior

Five modeling teams from industry and academia were chosen by the NASA Aviation Safety and Security Program to develop human performance models (HPM) of pilots performing taxi operations and runway instrument approaches with and without advanced displays. One representative from each team will serve as a panelist to discuss their team s model architecture, augmentations and advancements to HPMs, and aviation-safety related lessons learned. Panelists will discuss how modeling results are influenced by a model s architecture and structure, the role of the external environment, specific modeling advances and future directions and challenges for human performance modeling in aviation