18,118 research outputs found

    Association between the AHA Life's Essential 8 score and incident all-cause dementia: a prospective cohort study from UK Biobank

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    Aim: This study aimed to investigate the association between the LE8 score and incident all-cause dementia (including Alzheimer's disease [AD] and vascular dementia) in UK Biobank. Methods: 259,718 participants were included in this prospective study. Smoking, non-HDL cholesterol, blood pressure, body mass index, HbA1c, physical activity, diet, and sleep were used to create the LE8 score. Associations between the score (both continuous and as quartiles) and outcomes were investigated using adjusted linear and nonlinear Cox proportional hazard models. The potential impact fractions of two scenarios and the rate advancement periods were also calculated. Results: Over a median follow-up of 10.6 years, 4,958 participants were diagnosed with any dementia. Higher LE8 scores were associated with lower risk of all-cause and vascular dementia in an exponential decay pattern. Compared with individuals in the healthiest quartile, those in the least healthy quartile had a higher risk of all-cause dementia (HR: 1.50 [95% CI: 1.37 to 1.65] and vascular dementia (HR: 1.86 [1.44 to 2.42]). A targeted intervention that increased, by 10-points, the score among individuals in the lowest quartile could have prevented 6.8% of all-cause dementia cases. Individuals in the least healthy LE8 quartile might develop all-cause dementia 2.45 years earlier than their counterparts. Conclusions: Individuals with higher LE8 scores had lower risk of all-cause and vascular dementia. Because of nonlinear associations, interventions targeted at the least healthy individuals might produce greater population-level benefits

    CAR-DESPOT: Causally-Informed Online POMDP Planning for Robots in Confounded Environments

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    Robots operating in real-world environments must reason about possible outcomes of stochastic actions and make decisions based on partial observations of the true world state. A major challenge for making accurate and robust action predictions is the problem of confounding, which if left untreated can lead to prediction errors. The partially observable Markov decision process (POMDP) is a widely-used framework to model these stochastic and partially-observable decision-making problems. However, due to a lack of explicit causal semantics, POMDP planning methods are prone to confounding bias and thus in the presence of unobserved confounders may produce underperforming policies. This paper presents a novel causally-informed extension of "anytime regularized determinized sparse partially observable tree" (AR-DESPOT), a modern anytime online POMDP planner, using causal modelling and inference to eliminate errors caused by unmeasured confounder variables. We further propose a method to learn offline the partial parameterisation of the causal model for planning, from ground truth model data. We evaluate our methods on a toy problem with an unobserved confounder and show that the learned causal model is highly accurate, while our planning method is more robust to confounding and produces overall higher performing policies than AR-DESPOT.Comment: 8 pages, 3 figures, submitted to 2023 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS

    Considerations for Master Protocols Using External Controls

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    There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a basket trial, an umbrella trial, a platform trial, or any other form of trials in which multiple drugs and/or multiple subpopulations are studied in parallel under a single protocol. External data and evidence (EDE) can be used in the design and analysis of master protocols such as external controls for treatment effect estimation, which can further improve efficiency of the master protocol trial. This paper provides an overview of different types of external controls and their unique features when used in master protocols. Some key considerations in master protocols with external controls are discussed including construction of estimands and assessment of fit-for-use real-world data. A targeted learning-based causal roadmap is presented which constitutes three key steps: (1) define a target statistical estimand that aligns with the causal estimand for the study objective, (2) use an efficient estimator to estimate the target statistical estimand and its uncertainty, and (3) evaluate the impact of causal assumptions on the study conclusion by performing a sensitivity analysis. Two illustrative examples are provided for master protocols using external controls

    Effects of the COVID-19 pandemic on the mental health of clinically extremely vulnerable children and children living with clinically extremely vulnerable people in Wales: a data linkage study

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    Objectives: To determine whether clinically extremely vulnerable (CEV) children or children living with a CEV person in Wales were at greater risk of presenting with anxiety or depression in primary or secondary care during the COVID-19 pandemic compared with children in the general population and to compare patterns of anxiety and depression during the pandemic (23 March 2020–31 January 2021, referred to as 2020/2021) and before the pandemic (23 March 2019–31 January 2020, referred to as 2019/2020), between CEV children and the general population. Design: Population-based cross-sectional cohort study using anonymised, linked, routinely collected health and administrative data held in the Secure Anonymised Information Linkage Databank. CEV individuals were identified using the COVID-19 shielded patient list. Setting: Primary and secondary healthcare settings covering 80% of the population of Wales. Participants: Children aged 2–17 in Wales: CEV (3769); living with a CEV person (20 033); or neither (415 009). Primary outcome measure: First record of anxiety or depression in primary or secondary healthcare in 2019/2020 and 2020/2021, identified using Read and International Classification of Diseases V.10 codes. Results: A Cox regression model adjusted for demographics and history of anxiety or depression revealed that only CEV children were at greater risk of presenting with anxiety or depression during the pandemic compared with the general population (HR=2.27, 95% CI=1.94 to 2.66, p<0.001). Compared with the general population, the risk among CEV children was higher in 2020/2021 (risk ratio 3.04) compared with 2019/2020 (risk ratio 1.90). In 2020/2021, the period prevalence of anxiety or depression increased slightly among CEV children, but declined among the general population. Conclusions: Differences in the period prevalence of recorded anxiety or depression in healthcare between CEV children and the general population were largely driven by a reduction in presentations to healthcare services by children in the general population during the pandemic

    Effectiveness of Rectangular Rapid Flashing Beacons (RRFBs) in Small and Rural Communities

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    Ensuring the safety of pedestrians and cyclists in rural and small communities is becoming increasingly important as planners seek to encourage active travel and eliminate traffic-related injuries and fatalities, consistent with Vision Zero. One area of focus is the protection of vulnerable road users such as pedestrians, who face a significant risk of injury or death in a traffic collision. The risks to pedestrians are particularly high when crossing roadways in high-risk areas such as high-speed and low pedestrian-volume rural roads and between intersections where drivers may not expect them. One concern in rural communities is that pedestrians may face a heightened risk in rural transition zones as they approach the boundary of a city, town, or village from a higher-speed rural highway. In these settings drivers’ perceptions may lag behind their changing surroundings, and their awareness of reduced speed limits and the presence of pedestrians may be diminished. This report addresses the need to evaluate the effectiveness of RRFBs in rural and small communities. We first review prior literature on RRFB effectiveness to synthesize research insights that provide contextspecific guidance for their use as well as gaps in this literature. To supplement this body of research, we use a rigorous observational research design to evaluate the effectiveness of RRFBs within the unique context of small and rural communities in Vermont. Our results are used to provide recommendations for updating Vermont\u27s RRFB guidelines

    Functional forms of socio-territorial inequities in breast cancer screening - A French cross-sectional study using hierarchical generalised additive models

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    To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake. We used two-level hierarchical generalised additive models in 8 types of territories classified by socio-demographic and economic factors. The first level was 368,201 women aged 50-72 invited to the 2013-2014 screening campaign in metropolitan France. They were nested in 41 départements, the level of organisation of the FNOBCSP. The effect of travel time showed two main patterns: it was either linear (with participation decreasing as travel time increased) or participation first increased with increasing travel time to a peak around 5-15 min and decreased afterward. In nearly all types and départements, the probability of participation decreased linearly with increasing deprivation. Territorial inequities in participation were more context-dependent and complex than social inequities. Inequities in participation represent a loss of opportunity for individuals who already have the worst cancer outcomes. Evidence-based public health policies are needed to increase the effectiveness and equity of breast cancer screening

    Evaluation of birth by cesarean delivery and development of early-onset colorectal cancer

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    IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited. OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring. DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC were matched with each case on age, sex, calendar year, and county of residence. Pathology-confirmed end points were linked with the Swedish Medical Birth Register and other national registers. Analyses were conducted from March 2022 through March 2023. EXPOSURE: Birth by cesarean delivery. MAIN OUTCOMES AND MEASURES: The primary outcome was development of early-onset CRC in the overall population and by sex. RESULTS: We identified 564 case patients with incident early-onset CRC (mean [SD] age, 32.9 [6.2] years; 284 [50.4%] male) and 2180 matched controls (mean [SD] age, 32.7 [6.3] years; 1104 [50.6%] male). Compared with vaginal delivery, birth by cesarean delivery was not associated with early-onset CRC in the overall population (adjusted odds ratio [aOR], 1.28; 95% CI, 0.91-1.79) after multivariable adjustment for matching and maternal and pregnancy-related factors. A positive association was found for females (aOR, 1.62; 95% CI, 1.01-2.60), but there was no association for males (aOR, 1.05; 95% CI, 0.64-1.72). CONCLUSIONS AND RELEVANCE: In this nationwide, population-based case-control study, birth by cesarean delivery was not associated with early-onset CRC compared with birth by vaginal delivery in the overall population in Sweden. However, females born by cesarean delivery had greater odds of early-onset CRC compared with individuals born through vaginal delivery. This finding suggests that early-life gut dysbiosis may contribute to early-onset CRC in females

    Advance care planning and health-related quality of life in Huntington disease: Results from a multicenter national study

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    OBJECTIVE: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months. METHODS: HD-validated clinician- and patient-assessments (i.e., HRQoL PROs) were obtained at baseline enrollment, 12 and 24 months through our multi-center study (HDQLIFE™) throughout the United States among people with premanifest, early-stage, and late-stage manifest HD. We used linear mixed-effects models to determine the relationships between STB and HRQoL at baseline and HDQLIFE End of Life Planning at follow-up. Separate linear mixed-effects models were used to assess the relationship between HDQLIFE End of Life Planning at baseline, and HRQoL and STB at 12 and 24 months. False discovery rate adjustments were used to account for multiple comparisons. RESULTS: At baseline enrollment, STB and HRQoL were not related to HDQLIFE End of Life Planning at 12 or 24 months. Similarly, at baseline, HDQLIFE End of Life Planning demonstrated no association with STB or HRQoL at 12 or 24 months. INTERPRETATION: STB and HRQoL PROs do not significantly affect patient engagement with ACP. Most importantly, engaging in ACP does not cause untoward effects on HRQoL or STB for this rare neurodegenerative disease where the lifetime prevalence of STB approaches 30%
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