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Abstract Background Research on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited. Methods Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed. Results During a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene. Conclusion Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

Abstract Background The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD). Methods Post hoc analysis using a target trial emulation framework applied to the immediate post-trial period (2017–2021) of a study of low-dose aspirin initiation in adults aged ≥ 70 years (ASPREE; NCT01038583). Participants from Australia and the USA were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0. The two groups in the target trial were as follows: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term) and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models. Results We included 6103 CVD-free participants (cessation: 5427, continuation: 676). Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE, and all-cause mortality (HRs, at 3 and 48 months respectively, were 1.23 and 0.73 for CVD, 1.11 and 0.84 for MACE, and 0.23 and 0.79 for all-cause mortality, p > 0.05), but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p

Background and aims Gallstone disease affects ≥40 million people in the USA and accounts for health costs of ≥$4 billion a year. Risk factors such as obesity and metabolic syndrome are well established. However, data are limited on relevant metabolomic alterations that could offer mechanistic and predictive insights into gallstone disease. This study prospectively identifies and externally validates circulating prediagnostic metabolites associated with incident gallstone disease.Methods Female participants in Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS II) who were free of known gallstones (N=9960) were prospectively followed up after baseline metabolomic profiling with liquid chromatography–tandem mass spectrometry. Multivariable logistic regression and enrichment analysis were used to identify metabolites and metabolite groups associated with incident gallstone disease at PFDR

Dietary patterns contribute to overall health and diseases of ageing but are understudied in older adults. As such, we first aimed to develop dietary indices to quantify Mediterranean Diet Score (MDS) utilisation and Ultra-processed Food (UPF) intake in a well-characterised cohort of relatively healthy community-dwelling older Australian adults. Second, we aimed to understand the relationship between these scores and the association of these scores with prevalent cardiometabolic disease and frailty. Our major findings are that in this population of older adults, (a) pre-frailty and frailty are associated with reduced MDS and increased UPF intake; (b) adherence to MDS eating patterns does not preclude relatively high intake of UPF (and vice versa); and (c) high utilisation of an MDS eating pattern does not prevent an increased risk of frailty with higher UPF intakes. As such, the Mediterranean Diet pattern should be encouraged in older adults to potentially reduce the risk of frailty, while the impact of UPF intake should be further explored given the convenience these foods provide to a population whose access to unprocessed food may be limited due to socioeconomic, health, and lifestyle factors.

Introduction Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE–vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self–care materials, and health-related quality of life.Methods and analysis Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes.Ethics and dissemination The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care.Trial registration number NCT04966104

BackgroundZero-time Exercise (ZTEx), a simple strength- and stamina-enhancing physical activity (PA) requiring no extra equipment, can potentially increase PA and fitness. This pilot trial examined the feasibility and potential effectiveness of a smartphone ZTEx intervention to promote PA and fitness in patients with coronary heart disease (CHD).MethodsA parallel-group assessor-blinded pilot randomized controlled trial was conducted on Chinese patients with stable coronary heart disease (CHD) in three cardiology clinics. The experimental group received a 15-min brief individual face-to-face session and a 12-week ZTEx instant messaging with 28 picture e-messages and a smartphone ZTEx application (ZTExApp). The control group received the same duration of individual session and number and format of e-messages, but the content was healthy eating and breathing exercise. The feasibility was assessed based on: attrition rate, usage, response rate and perception of the intervention. The outcome evaluation included primary outcome (PA), fitness, exercise self-efficacy and intention, perceived happiness and health, and quality of life. A linear mixed model was used with intention-to-treat analysis adjusting for sex, age and baseline values. A semi-structured interview was conducted to collect feedback from the experiment group.ResultsOne hundred thirty-nine patients (mean age 59.8 ± 6.6; 71.2% male) were randomized to the experimental group (n = 70) or control group (n = 69), and 80% (56/70) and 82% (57/69) of patients completed the 12-week follow-up assessment, respectively. The attrition rate was 18.7%. The experimental group reported that ZTEx was feasible to integrate PA into their daily life and appreciated the picture e-messages, and 95% of them sent feedback to us, but only 19.6% (13/70) of the participants entered their PA information into the e-diary of the ZTExApp. The experimental group had a significantly greater increase in time spent walking [mean difference (95% CI): 155.3 (10.1, 300.4), P = 0.04, Cohen's d = 0.34] than the control group.ConclusionsThis pilot study showed using a brief ZTEx face-to-face session with picture e-messages empowered patients with CHD to integrate PA into daily life. Future definitive trials with a longer follow-up and a more user-friendly ZTExApp interface are necessary to determine the effectiveness of the smartphone ZTEx intervention in enhancing PA and related outcomes.Trial RegistrationThe research protocol was registered at the Hong Kong University Clinical Trials Registry (HKUCTR) on 22 Jul 2016 (Study identifier: HKUCTR-2165) and was also retrospectively registered at the National Institutes of Health (identifier number: NCT03464331) on 14 March 2018.

Abstract Capturing TC intensity change remains a great challenge for most state‐of‐the‐art operational forecasting systems. Recent studies found TC intensity forecasts are sensitive to three‐dimensional ocean dynamics and air‐sea interface processes beneath extreme winds. By performing a series of numerical simulations based on hierarchical atmosphere‐wave‐ocean (AWO) coupling configurations, we showed how atmosphere‐ocean and atmosphere‐sea wave coupling can affect the intensity of super typhoon Mangkhut (2018). The AWO coupled model can simulate TC‐related strong winds, oceanic cold wake, and wind waves with high fidelity. With atmosphere‐ocean (AO) coupling implemented, the simulated maximum surface wind speed is reduced by 7 m s−1 compared to the atmosphere‐only run, due to TC‐induced oceanic cold wakes in the former experiment. In the fully coupled AWO simulations, the wind speed deficit can be completely compensated by the wave‐air coupling effect. Further analyses showed that, in the AWO experiment, two mechanisms contribute to the improvement of TC intensity. First, in the high wind scenario (>28 m s−1), the surface drag coefficient reaches an asymptotic level, assisting extreme wind speed to be maintained within the eyewall. Second, the wind speed distribution is modulated and becomes broader; higher wind within the TC area helps to offset the negative effect due to leveling off of the heat exchange coefficient as wind speed increases. Overall, the simulated TC in the AWO run can extract 8–9% more total heat energy from the ocean to maintain its strength, compared to that from the AO experiment.

The gut microbiome is increasingly recognized to play a role in cognition and dementia. Antibiotic use impacts the gut microbiome and has been linked with chronic disease. Despite these data, there is no evidence supporting an association between long-term antibiotic use in adults and cognitive function. We conducted a prospective population-based cohort study among 14,542 participants in the Nurses' Health Study II who completed a self-administered computerized neuropsychological test battery between 2014-2018. Multivariate linear regression models were used to assess if chronic antibiotic use in midlife was associated with cognitive impairment assessed later in life. Women who reported at least 2 months of antibiotic exposure in midlife (mean age 54.7, SD 4.6) had lower mean cognitive scores seven years later, after adjustment for age and educational attainment of the spouse and parent, with a mean difference of -0.11 standard units for the global composite score (Ptrend