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Abstract Background Previous research on the association between physical activity (PA) and kidney function is inconsistent. The association between muscle mass and serum creatinine (SCr) may have implications for interpreting the effect of PA on estimated glomerular filtration rate (eGFR). Few studies have reported changes in physical activity and changes in kidney function. Methods A cohort study was constructed using the UK Biobank. Changes in physical activity were self‐reported as metabolic equivalent task (MET) minutes/week. eGFR was calculated using SCr and cystatin C (CysC). Cox and nonlinear regressions with restricted cubic splines were applied to explore the association between changes in physical activity and rapid decline of kidney function (RDKF, eGFR annual decrease ≥3 mL/min/1.73 m2), and the annual change of eGFR. An exploratory analysis of cardiorespiratory fitness as the exposure was conducted. Results Among 11 757 participants, the median follow‐up time was 4.4 years. Participants whose PA decreased by 1000 MET minutes/week at the follow‐up assessment had a 2% reduction in risk of developing RDKFSCr (HR = 0.98, 95% CI: 0.96, 1.00). In contrast, a 1000 MET minutes/week increase in PA was associated with a 4% reduction in risk of developing RDKFCysC (HR = 0.96, 95% CI: 0.93, 0.99). A PA increase of 1000 MET minutes/week was associated with eGFRCysC annual increase of 0.04 mL/min/1.73 m2 (95% CI: 0.03, 0.06) but no significant changes in eGFRSCr. Conclusions In this general population study, there are differing associations between changes in PA and changes in kidney function depending on the kidney biomarker used. Increasing PA is modestly associated with improving annual eGFRCysC and reduced risk of RDKF.

Abstract It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcohol consumption and diet were self-reported. The diet score was created from 4 items selected using LASSO. Cox proportional hazard model showed that the diet score was monotonically associated with severe ALD risk, adjusted for sociodemographics, lifestyle factors, and alcohol consumption. Relative excess risk due to interaction analysis indicated that having a higher ALD diet score and a higher alcohol consumption simultaneously confers to 2.44 times (95% CI: 1.06-3.83) higher risk than the sum of excess risk of each factor. In this work, we show that people who have a poor diet might be more susceptible to severe ALD due to alcohol consumption.

Abstract Background Obesity and central obesity are multifactorial conditions with genetic and non-genetic (lifestyle and environmental) contributions. There is incomplete understanding of whether lifestyle modifies the translation from respective genetic risks into phenotypic obesity and central obesity, and to what extent genetic predisposition to obesity and central obesity is mediated via lifestyle factors. Methods This is a cross-sectional study of 201,466 (out of approximately 502,000) European participants from UK Biobank and tested for interactions and mediation role of lifestyle factors (diet quality; physical activity levels; total energy intake; sleep duration, and smoking and alcohol intake) between genetic risk for obesity and central obesity. BMI-PRS and WHR-PRS are exposures and obesity and central obesity are outcomes. Results Overall, 42.8% of the association between genetic predisposition to obesity and phenotypic obesity was explained by lifestyle: 0.9% by mediation and 41.9% by effect modification. A significant difference between men and women was found in central obesity; the figures were 42.1% (association explained by lifestyle), 1.4% (by mediation), and 40.7% (by modification) in women and 69.6% (association explained by lifestyle), 3.0% (by mediation), and 66.6% (by modification) in men. Conclusions A substantial proportion of the association between genetic predisposition to obesity/central obesity and phenotypic obesity/central obesity was explained by lifestyles. Future studies with repeated measures of obesity and lifestyle would be needed to clarify causation.

Objectives: To investigate the associations of n-3 fatty acid intake with handgrip strength and muscle mass indices in older adults. A secondary aim was to investigate whether these associations differed by physical activity status. Research methods & procedures: A cross-sectional study included 53,170 participants aged 60 years and over from the UK biobank (25,324 men and 27,846 women). The primary outcomes were grip strength index and muscle mass index, the predictor variable was n-3 fatty acid intake and the covariates were age, ethnicity, Townsend deprivation index, physical activity, multimorbidity count, total energy intake, body fat percentage and the month of assessment. Multivariable linear regression analyses were performed across 5 models. Model 1 was unadjusted; model 2 adjusted for age, ethnicity, deprivation index and month of assessment; model 3 adjusted as in model 2 plus total energy intake; model 4 as in model 2 plus multimorbidity count; and model 5 as in model 4 plus body fat percentage. Results: In model 5, higher n-3 fatty acid intake was positively associated with the grip strength index in women. For each additional gram of n-3 fatty acid consumed per day, there was an increase of 0.03 kg/m2 (95% CI: 0.00 to 0.06 kg/m2) in active women and 0.04 kg/m2 (95% CI: 0.00 to 0.07 kg/m2) in inactive women. However, no significant associations were observed in men, whether active (p = 0.405) or inactive (p = 0.323). Additionally, no significant associations were found between n-3 fatty acid intake and muscle mass index in either active (p = 0.858) or inactive (p = 0.250) men, or in active (p = 0.909) or inactive (p = 0.187) women. Conclusion: Although n-3 fatty acid intake was associated with grip strength index in older women, regardless of their activity status, the magnitude of this association was very small and unlikely to be clinically relevant. Additionally, n-3 fatty acid was not associated with muscle mass index.

Summary: Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014–2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17–89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.Methods Data from hospitalized subjects with Glasgow Coma Scale score of 3–12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014–2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1–3 (vs. 4–8)) at 3, 6, and 12 months after injury.Results Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01–4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.Conclusions After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.Level of evidence IV.Trial registration number NCT02119182.

Abstract Background Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations. Methods We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables. Results Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p

Background Previous studies suggest an association between schizophrenia and stroke, but no studies have investigated stroke subtypes. We examined potential causal associations between schizophrenia and a range of atherosclerotic, embolic, and hemorrhagic stroke outcomes. Methods and Results Two‐sample Mendelian randomization analyses were conducted. The summary‐level data (restricted to European ancestry) were obtained for schizophrenia and stroke: ischemic stroke, large‐artery stroke, small‐vessel stroke, cardioembolic stroke, and intracerebral hemorrhage. The associations between schizophrenia and each outcome were analyzed by an inverse variance weighting method primarily and Mendelian randomization Egger, weighted median, and weighted mode subsequently. The presence of pleiotropy was also tested by Cochran Q statistic, I2 index, and Mendelian randomization Egger intercept with scatter and funnel plots. We found associations between schizophrenia and cardioembolic stroke (odds ratio [OR], 1.070 [95% CI, 1.023–1.119]) and intracerebral hemorrhage (OR, 1.089 [95% CI, 1.005–1.180]) using inverse variance weighting. Little evidence of associations with the other stroke subtypes was found. Different Mendelian randomization methods corroborated the association with cardioembolic stroke but not intracerebral hemorrhage. Conclusions We have provided evidence of a potentially causal association between schizophrenia and cardioembolic stroke. Our findings suggest that cardiac evaluation should be considered for those with schizophrenia.

Abstract Background The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based recommendations which aim to reduce cancer risk. This study investigated associations between adherence, assessed using a standardised scoring system, and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with aspects of lifestyle in the UK. Methods We used data from 94,778 participants (53% female, mean age 56 years) from the UK Biobank. Total adherence scores (range 0–7 points) were derived from dietary, physical activity, and anthropometric data. Associations between total score and cancer risk (all cancers combined; and prostate, breast, colorectal, lung, uterine, liver, pancreatic, stomach, oesophageal, head and neck, ovarian, kidney, bladder, and gallbladder cancer) were investigated using Cox proportional hazard models, adjusting for age, sex, deprivation index, ethnicity, and smoking status. Results Mean total score was 3.8 (SD 1.0) points. During a median follow-up of 8 years, 7296 individuals developed cancer. Total score was inversely associated with risk of all cancers combined (HR: 0.93; 95%CI: 0.90–0.95 per 1-point increment), as well as breast (HR: 0.90; 95%CI: 0.86–0.95), colorectal (HR: 0.90; 95%CI: 0.84–0.97), kidney (HR: 0.82; 95%CI: 0.72–0.94), oesophageal (HR: 0.84; 95%CI: 0.71–0.98), ovarian (HR: 0.76; 95%CI: 0.65–0.90), liver (HR: 0.78; 95%CI: 0.63–0.97), and gallbladder (HR: 0.70; 95%CI: 0.53–0.93) cancers. Conclusions Greater adherence to lifestyle-based recommendations was associated with reduced risk of all cancers combined and of breast, colorectal, kidney, oesophageal, ovarian, liver, and gallbladder cancers. Our findings support compliance with the Cancer Prevention Recommendations for cancer prevention in the UK.

Introduction: Euglycemic diabetic ketoacidosis (DKA) (glucose 18 years old, met criteria for DKA on initial laboratories (pH ≤7.30, serum bicarbonate ≤18 millimoles per liter [mmol/L], anion gap ≥10), and were managed via a standardized DKA order set. Patients were divided into euglycemic (18 mmol/L and first long-acting insulin were similar. Incidence of hypoglycemia (

BackgroundEvidence supports the effectiveness of serious games in health education, but little is known about their effects on the psychosocial well-being of children in the general population. ObjectiveThis study aimed to investigate the potential of a mobile game–based safety education program in improving children’s safety and psychosocial outcomes. MethodsSafe City is a mobile roleplaying game specifically designed to educate children in Hong Kong about safety. This randomized controlled trial included 340 children in grades 4 through 6. Intervention arm participants (n=170) were instructed to play the Safe City mobile game for 4 weeks, whereas control arm participants (n=170) received a safety booklet. All participants completed a survey on safety knowledge and behaviors and psychosocial problems at baseline (T1), 1 month postintervention (T2), and 3 months postintervention (T3). Cumulative game scores and mini-game performance were analyzed as a proxy for the extent of exposure to the game. Outcome data were analyzed using 2-sample 2-tailed t tests to compare mean change from T1 to T2 and to T3 for intervention versus control arm participants. The association of game use with outcome changes postintervention was analyzed using generalized additive models. ResultsNo significant differences were found in mean changes between the intervention and control arms. However, use analyses showed that higher game scores were associated with improvements in safe behavior (P=.03) and internalizing problems (P=.01) at T3. Matching and Spot the Danger mini-game performance significantly predicted improvements in safety knowledge at T2 and T3. ConclusionsAnalysis of use has shown that playing the Safe City mobile game can result in significant improvements in safety knowledge and reductions in unsafe behavior and internalizing problems. These findings provide evidence for the positive impact of serious games on psychological and social well-being, highlighting the potential of technology-driven interventions to assist children in learning about safety and preventing injuries. Trial RegistrationClinicalTrials.org NCT04096196; https://clinicaltrials.gov/show/NCT04096196 International Registered Report Identifier (IRRID)RR2-10.2196/17756

Patella alta is a clinical condition where the patella is positioned too proximal in relation to the femoral trochlea. Such an abnormality may cause patellar instability and predispose to recurrent patellofemoral dislocations and patellofemoral pain. There are no conclusive guidelines for determining a threshold for too high positioned patella, as several different methods have been described to measure patellar height. As a surgical solution, distalising tibial tubercle osteotomy has been described to correct excessive patellar height. In the early phase of the distalising tibial tubercle osteotomy postoperative protocol, weightbearing and knee flexion are limited with a brace commonly for 4-8 weeks to avoid potential implant failure leading to displacement of the osteotomy or non-union. The potential risks for adverse effects associated with the limitation rehabilitation protocol include a delay in regaining knee range of motion, stiffness and muscle weakness. As a result, recovery from surgery is delayed and may lead to additional procedures and long-term morbidity in knee function. This is a prospective, randomised, controlled, single-blinded, single centre trial comparing a novel accelerated rehabilitation protocol with the traditional, motion restricting rehabilitation protocol. All skeletally mature patients aged 35 years and younger, referred to as the distalising tibial tubercle osteotomy procedure group, are eligible for inclusion in the study. Patients will be randomised to either the fast rehabilitation group or the traditional rehabilitation group. Patients with patellar instability will be additionally treated with medial patellofemoral ligament reconstruction. The hypothesis of the trial is that the novel accelerated rehabilitation protocol will lead to faster recovery and improved functional outcome at 6, 12 and 24 weeks compared with the conservative rehabilitation protocol. A secondary hypothesis is that the complication rate will be similar in both groups. The study will document short-term recovery and the planned follow-up will be 3 years. After the 1-year follow-up, the trial results will be disseminated in a major peer-reviewed orthopaedic publication. Protocol version 3.6, date 28/11/2023.

Background: Brain Health Index (BHI) assimilates various MRI sequences, giving a quantitative measure of brain health. To date, BHI validation has been cross-sectional and limited to selected populations. Further large-scale validation and assessment of temporal change is required to understand its clinical utility. Aim: Assess 1) relationships between variables associated with cognitive decline and BHI 2) associations between BHI and measures of cognition and 3) longitudinal changes in BHI and relationship with cognitive function. Methods: BHI computation involved Gaussian mixture-model cluster analysis of T1, T2, T2*, and T2 FLAIR MRI data from participants within the European Prevention of Alzheimer's Dementia (EPAD) cohort. Group differences (gender- and health-based) were evaluated using independent samples Welch's t-tests. Relationships between BHI, age and cognitive tests used linear regression. Longitudinal analysis (12/24 months) utilised mixed linear regression models to examine BHI changes, and paired BHI/cognition associations. Results: Data from N = 1496 predominantly Caucasian participants (50–88 years old, 43.32% male) were used. BHI scores were lower in those with diabetes (p < 0.001, d = 0.419), hypertension (p < 0.001, d = 0.375), hypercholesterolemia (p < 0.001, d = 0.193) and stroke (p < 0.05, d = 0.512). APOE was not significantly related to BHI scores. After correction for age, cross-sectional BHI scores were significantly associated with all measures of cognitive function in males, but only the Four Mountains Test (4MT) in females. Longitudinal change in BHI and cognition were not consistently related. Conclusions: BHI is a valid marker of cognitive decline and relatively stable over 1-2 year follow-up periods. Further work should assess temporal changes over a longer duration and determine relationships between BHI and cognition in more diverse populations.

Abstract Background Most studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose–response relationship between device-measured PA and incident type 2 diabetes. Methods This prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework. Results The median follow-up period was 6.3 years (IQR: 5.7–6.8), with 591 participants developing type 2 diabetes. Compared to those achieving 600 min/week were at 49% (95% CI 62–32%), 62% (95% CI 71–50%) and 71% (95% CI 80–59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving 75 min/week were at 38% (95% CI 48–33%), 48% (95% CI 64–23%) and 64% (95% CI 78–42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively. Conclusions PA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction. Trial registration The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011).

Abstract Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both pre-and post-treatment testing with the same 42-gene MRD-validated NGS assay. After induction, 59 (46%) patients were mutation-negative (0.0024 VAF detection limit) and 69 (54%) had ≥1 persisting NGS-detectable mutation. Compared with NGS-negative patients, NGS-positive patients had shorter overall survival (17 months versus median not reached; P = 0.004; hazard ratio = 2.2 [95% CI: 1.3–3.7]) and a shorter time to relapse (14 months versus median not reached; P = 0.014; HR = 1.9 [95% CI: 1.1–3.1]). Among 95 patients with a complete morphologic remission (CR), 43 (45%) were MRD-positive by NGS and 52 (55%) were MRD-negative. These MRD-positive CR patients had a shorter overall survival (16.8 months versus median not reached; P = 0.013; HR = 2.1 [95% CI: 1.2–3.9]) than did the MRD-negative CR patients. Post-treatment persisting MRD positivity, defined by the same NGS-based test used at diagnosis, is thus a more sensitive biomarker for low-level leukemic clones compared to traditional non-molecular methods and is prognostic of subsequent relapse and death.

Abstract Background Although non-alcoholic fatty liver disease (NAFLD) is linked to inflammation, whether an inflammatory diet increases the risk of NAFLD is unclear. This study aimed to examine the association between the Energy-adjusted Diet Inflammatory Index (E-DII) score and severe NAFLD using UK Biobank. Methods This prospective cohort study included 171,544 UK Biobank participants. The E-DII score was computed using 18 food parameters. Associations between the E-DII and incident severe NAFLD (defined as hospital admission or death) were first investigated by E-DII categories (very/moderately anti-inflammatory [E-DII 1]) using Cox proportional hazard models. Nonlinear associations were investigated using penalised cubic splines fitted into the Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. Results Over a median follow-up of 10.2 years, 1489 participants developed severe NAFLD. After adjusting for confounders, individuals in the very/moderately pro-inflammatory category had a higher risk (HR: 1.19 [95% CI: 1.03 to 1.38]) of incident severe NAFLD compared with those in the very/moderately anti-inflammatory category. There was some evidence of nonlinearity between the E-DII score and severe NAFLD. Conclusions Pro-inflammatory diets were associated with a higher risk of severe NAFLD independent of confounders such as the components of the metabolic syndrome. Considering there is no recommended treatment for the disease, our findings suggest a potential means to lower the risk of NAFLD.

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

OBJECTIVES/GOALS: A TIA is a transient episode of symptoms attributed to a cerebrovascular cause, and associated with an increased risk of stroke. Care of these patients often requires substantial resources in the Emergency Department (ED). We therefore described neuroimaging and hospitalization use for TIA within a nationally representative sample of US ED visits. METHODS/STUDY POPULATION: Retrospective cross-sectional analysis using TIA encounters in the 2018 National Emergency Department Sample (NEDS), an AHRQ dataset consisting of a weighted sample of 20% of all US ED encounters. Non-contrast Head CT, CTA Head, Carotid Ultrasound, MRI and CT Perfusion imaging utilization was determined based on Common Procedural Terminology (CPT) codes in the non-admitted encounters. The study population includes all adult patients with a discharge diagnosis of TIA as determined by ICD-10 codes (H34.0, G45.0-3, G45.8 G45.9) in any diagnosis position. The percentage of patients receiving each neuroimaging test was reported with the corresponding 95% confidence interval (CI). We utilized survey sample weights to generate reliable national estimates. RESULTS/ANTICIPATED RESULTS: The study population consisted of 80,803 ED encounters with a discharge diagnosis of TIA, representing 326,802 weighted ED visits nationally. Among this group, 46.8% of patients were discharged and 41.8% were admitted to the same hospital, 7% of patients were transferred to another facility, and the remaining 5% left AMA, were dispositioned to home health, died in the ED, or had an unknown disposition. Because discharged encounters retain their more precise CPT coding of procedural information, imaging analysis was conducted in discharged TIA encounters only. Of these encounters, 73% (95% CI, 70.7-76.5) received a noncontrast head CT, 20.9% (95% CI, 19.1-22.7) a CTA Head, 22.5% (95% CI, 20.6-24.4) a carotid ultrasound, and 31.5% (95% CI, 29.3-33.7) an MRI brain without contrast. DISCUSSION/SIGNIFICANCE: The discharge rate of just under 50% of patients is consistent with other published data, and represents a gradual trend over the past decade of decreased admissions for TIA. The fact that for many of these patients, the entire episode of care occurs in the ED setting suggests that the ED may be a rich target for future innovations in care for TIA.

Background: The Brain Health Index (BHI) is an automated approach to quantifying brain integrity, combining different types of structural magnetic resonance imaging (MRI). Normative values derived from generally healthy individuals provide a vital baseline for understanding neurodegenerative change. Although commonplace in other areas of medicine, these are not always established when proposing new analytical approaches using MRI. The scale and quality of the UK Biobank imaging cohort (approximately N = 50k, as of 2022) allows for derivation of such values, and the wealth of additional lifestyle, physiological and demographic data enables validation of BHI through comparison with more established variables which may affect brain health. Aim: This study aimed to: 1) establish normative BHI values in a cohort of ‘healthy’ participants, and 2) explore associations between BHI and risk factors for brain health. Methods: The BHI was computed using voxel-based Gaussian mixture model cluster analysis of T1 and T2 FLAIR MRI in a sub-cohort of UK Biobank participants. From these data, normative score curves – with bounds described as 1, 2 and 3 standard deviations from the mean – were produced for males and females, using regression analyses to measure the scale of the BHI values as a function of age. Additional Pearson’s correlation testing was used to examine known risk factors to brain health and their relationship to BHI scores, with t-tests and ANOVAs used to determine between-group differences in BHI scoring. Results: Data from 2,990 participants (50.07% male, 97.05% Caucasian, 43.6% with degree-level education) were used to derive normative BHI curves from 48 to 77 years old. BHI scores were higher in female than male participants (95% CI: 0.0103 to 0.0162, p

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Abstract Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.

Abstract Background Regular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, and the aim of the current study, therefore, is to test the hypothesis that vitamin K2 supplementation can accelerate recovery, via modulation of the underlying physiological processes, following a bout of resistance exercise in young and older adults. Methods The current study is a two-arm randomised controlled trial which will be conducted in 80 (40 young (≤40 years) and 40 older (≥65 years)) adults to compare post-exercise recovery in those supplemented with vitamin K2 or placebo for a 12-week period. The primary outcome is muscle strength with secondary outcomes including pain-free range of motion, functional abilities, surface electromyography (sEMG) and markers of inflammation and oxidative stress. Discussion Ethical approval has been granted by the College of Medical Veterinary and Life Sciences Ethical Committee at the University of Glasgow (Project No 200190189) and recruitment is ongoing. Study findings will be disseminated through a presentation at scientific conferences and in scientific journals. Trial registration ClinicialTrials.gov NCT04676958. Prospectively registered on 21 December 2020.

Abstract Background Studies on physical activity (PA) and mental health are largely limited to self-reported PA. This study aims to use prospective cohort data to investigate the association between device-measured PA and affective disorders. Methods A total of 37,327 participants from UK Biobank who had not had any prior affective disorder diagnoses were included in this prospective cohort study. Wrist-worn accelerometers were used to measure total, light (LPA), moderate (MPA), and vigorous (VPA) PA. Associations between PA domains and affective disorders were analysed using penalised splines in Cox proportional hazard models. Analyses were adjusted for other intensity-specific PA and sociodemographic and lifestyle factors. Sensitivity analyses were conducted adjusting for body mass index and longstanding illnesses as well as excluding events in the first 2 years of follow-up. Preventable fractions for the population were estimated for MPA and VPA. Results Over a median follow-up of 6.8 years, 1262 (3.4%) individuals were diagnosed with affective disorders. Replacing 30 min of sedentary behaviour in a week with MPA (HR 0.95, 95% CI 0.94–0.97) or VPA (HR 0.91, 95% CI 0.85–0.98) was associated with lower risk of affective behaviours, up to 500 and 120 min of MPA and VPA. Assuming causality, 5.14% and 18.88% of affective disorders could have been prevented if MPA ≥150 min/week and VPA ≥75 min/week were achieved, respectively, across the study population. Conclusions Device-measured MPA and VPA were associated with lower risk of affective disorders. The potential mental health benefits of MPA continue to accrue above the current World Health Organization recommendation.

BackgroundChinese handwriting has a close relationship with spatial cognition, and the legibility dimension is prominent with its spatial-oriented characteristics. However, handwriting evaluation focusing on the detailed spatial aspects of the legibility dimension in the Chinese context is rare.Aims and methodsWe aimed to develop a Chinese Handwriting Legibility Scale (CHLS) and examine its reliability, validity, and measurement invariance among Chinese primary students of different grades. A total of 684 students aged 8–12 years were recruited from a mainstream primary school in central China and were asked to copy a Chinese template as legibly as possible within 4 min. The developed CHLS was used to assess these students’ legibility performance.ResultsThe seven-criteria CHLS favored content validity. The inter-rater reliability was good; however, the scoring instructions need to be refined. Principal component analysis (PCA) revealed a one-factor solution explaining 62.336% of the variance of the seven-criteria CHLS, and confirmatory factor analysis (CFA) confirmed its appropriateness. There was a high internal consistency (α = 0.902). In terms of measurement invariance, the factor structures and loadings of the CHLS were consistent across students of different grades; however, significant intercept variations were detected between students of Grades 2 and 4.ConclusionCHLS may be effective for evaluating Chinese handwriting legibility performance in the Chinese primary school context in the central region. Students’ Chinese handwriting legibility performance may have developmental specificity in different grades.

PSR J0740+6620 is the neutron star with the highest precisely determined mass, inferred from radio observations to be 2.08 ± 0.07 M _⊙ . Measurements of its radius therefore hold promise to constrain the properties of the cold, catalyzed, high-density matter in neutron star cores. Previously, Miller et al. and Riley et al. reported measurements of the radius of PSR J0740+6620 based on Neutron Star Interior Composition Explorer (NICER) observations accumulated through 2020 April 17, and an exploratory analysis utilizing NICER background estimates and a data set accumulated through 2021 December 28 was presented in Salmi et al. Here we report an updated radius measurement, derived by fitting models of X-ray emission from the neutron star surface to NICER data accumulated through 2022 April 21, totaling ∼1.1 Ms additional exposure compared to the data set analyzed in Miller et al. and Riley et al., and to data from XMM-Newton observations. We find that the equatorial circumferential radius of PSR J0740+6620 is ${12.92}_{-1.13}^{+2.09}$ km (68% credibility), a fractional uncertainty ∼83% the width of that reported in Miller et al., in line with statistical expectations given the additional data. If we were to require the radius to be less than 16 km, as was done in Salmi et al., then our 68% credible region would become $R={12.76}_{-1.02}^{+1.49}$ km, which is close to the headline result of Salmi et al. Our updated measurements, along with other laboratory and astrophysical constraints, imply a slightly softer equation of state than that inferred from our previous measurements.

Abstract Background Depression and anxiety are the leading mental health problems worldwide; depression is ranked as the leading cause of global disability with anxiety disorders ranked sixth. Preventive strategies based on the identification of modifiable factors merit exploration. The aim of the present study was to investigate the associations of handgrip strength (HGS) with incident depression and anxiety and to explore how these associations differ by socio‐demographic, lifestyle, and health‐related factors. Methods The analytic sample comprised 162 167 participants (55% women), aged 38–70 years, from the UK Biobank prospective cohort study. HGS was assessed at baseline using dynamometry. Depression and anxiety were extracted from primary care and hospital admission records. Cox proportional models were applied, with a 2 year landmark analysis, to investigate the associations between HGS and incident depression and anxiety. Results Of the 162 167 participants included, 5462 (3.4%) developed depression and 6614 (4.1%) anxiety, over a median follow‐up period of 10.0 years (inter‐quartile range: 9.3–10.8) for depression and 9.9 (inter‐quartile range: 9.0–10.8) for anxiety. In the fully adjusted model, a 5 kg lower HGS was associated with a 7% (HR: 1.07 [95% CI: 1.05, 1.10]; P

Abstract Background This study aimed to investigate the associations of grip strength with incidence and mortality from dementia and whether these associations differ by sociodemographic and lifestyle factors. Methods A total of 466 788 participants of the UK Biobank (median age 56.5 years, 54.5% women). The outcome was all‐cause dementia incidence and mortality and the exposure was grip strength. Grip strength was assessed using a Jamar J00105 hydraulic hand dynamometer. Results Excluding the first 2 years of follow‐up (landmark analysis), mean follow‐up was 9.1 years (inter‐quartile range: 8.3; 9.7) for incidence and 9.3 (inter‐quartile range: 8.7; 10.0) for mortality. During this time, 4087 participants developed dementia, and 1309 died from it. Lower grip strength was associated with a higher risk of dementia incidence and mortality independent of major confounding factors (P

Abstract There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 [95% CI 6.36, 19.01]), attention deficit hyperactivity disorder (ADHD) (7.28 [5.49, 9.65]), and personality disorders (5.36 [3.78, 7.59]). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment.

Abstract This study investigated the status of equity in mathematics education in Hong Kong based on data from TIMSS 2011 to 2019 and the changes in education equity across the three cycles. The effects of various student-, family-, and school-level variables on students’ mathematics achievement were examined and compared using multilevel modeling. Results showed that there were significant variances between schools in mathematics achievement in Hong Kong, especially for eighth grade students. Overall, boys performed better in mathematics than girls in these three TIMSS cycles in Hong Kong, except for eighth grade boys in the cycles of 2011 and 2019. The family and school socio-economic status (SES) related to the possession of traditional materials (e.g., desks and books) and parents’ highest education level had positive and significant effects on students’ mathematics achievement, and the effects of the predictors increased from the 2011 cycle to the 2019 cycle. SES related to the possession of home digital devices (e.g., computers and internet connection) also had positive but much less substantial effects. School location and resource availability did not have significant effects. In general, the mean levels of SES and school resource availability in Hong Kong is improving. However, the effects of some important student- and school-level factors on mathematics achievement increased. Suggestions for improving education equity in Hong Kong are discussed.

Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximately 2-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) of a single unit of COVID-19 convalescent plasma (CCP) versus saline infusion. In a subset of 70 participants, peripheral blood mononuclear cells were obtained to define the evolution of B and T cell responses through day 30. Binding and neutralizing antibody responses were approximately 2-fold higher 1 hour after infusion in recipients of CCP compared with saline plus multivitamin, but levels achieved by the native immune system by day 15 were almost 10-fold higher than those seen immediately after CCP administration. Infusion of CCP did not block generation of the host antibody response or skew B or T cell phenotype or maturation. Activated CD4+ and CD8+ T cells were associated with more severe disease outcome. These data show that CCP leads to a measurable boost in anti–SARS-CoV-2 antibodies but that the boost is modest and may not be sufficient to alter disease course.

Abstract Background Ethnic differences in cardiovascular disease (CVD) risk have been known for decades, but a systematic exploration of how exposure and susceptibility to risk factors may contribute is lacking. This study aimed to investigate the potential impact of differential exposure and susceptibility between South Asian, Black, and White individuals. Methods This is a population-based prospective cohort study of UK Biobank participants with a median follow-up of 11.3 years. The association between ethnic group and CVD risk was studied. Additional risk factors were then adjusted to examine mediations. Moderation analysis was conducted to identify whether risk factors had a stronger association in the ethnic minority groups. Population attributable fractions were also calculated to quantify the relative contributions of risk factors for each ethnic group. Results When adjusted for only age and sex, there was a higher risk of CVD among South Asian (n=8815; HR [95% CI] 1.69 [1.59–1.79]) and Black (n=7526; HR [95% CI] 1.12 [1.03–1.22]) compared with White participants (n=434,809). The excess risk of Black participants was completely attenuated following adjustment for deprivation. Compared with White participants, the associations of BMI, triglycerides, and HbA1c with CVD were stronger in South Asians. Adiposity was attributable to the highest proportion of CVD regardless of ethnicity. Smoking had the second largest contribution to CVD among White and Black participants, and HbA1c among South Asian participants. Conclusions Adiposity is an important risk factor for CVD regardless of ethnicity. Ethnic inequalities in CVD incidence may be best tackled by targeting interventions according to ethnic differences in risk profiles.

Abstract Background Infection with SARS-CoV-2 virus (COVID-19) impacts disadvantaged groups most. Lifestyle factors are also associated with adverse COVID-19 outcomes. To inform COVID-19 policy and interventions, we explored effect modification of socioeconomic-status (SES) on associations between lifestyle and COVID-19 outcomes. Methods Using data from UK-Biobank, a large prospective cohort of 502,536 participants aged 37–73 years recruited between 2006 and 2010, we assigned participants a lifestyle score comprising nine factors. Poisson regression models with penalised splines were used to analyse associations between lifestyle score, deprivation (Townsend), and COVID-19 mortality and severe COVID-19. Associations between each exposure and outcome were examined independently before participants were dichotomised by deprivation to examine exposures jointly. Models were adjusted for sociodemographic/health factors. Results Of 343,850 participants (mean age > 60 years) with complete data, 707 (0.21%) died from COVID-19 and 2506 (0.76%) had severe COVID-19. There was evidence of a nonlinear association between lifestyle score and COVID-19 mortality but limited evidence for nonlinearity between lifestyle score and severe COVID-19 and between deprivation and COVID-19 outcomes. Compared with low deprivation, participants in the high deprivation group had higher risk of COVID-19 outcomes across the lifestyle score. There was evidence for an additive interaction between lifestyle score and deprivation. Compared with participants with the healthiest lifestyle score in the low deprivation group, COVID-19 mortality risk ratios (95% CIs) for those with less healthy scores in low versus high deprivation groups were 5.09 (1.39–25.20) and 9.60 (4.70–21.44), respectively. Equivalent figures for severe COVID-19 were 5.17 (2.46–12.01) and 6.02 (4.72–7.71). Alternative SES measures produced similar results. Conclusions Unhealthy lifestyles are associated with higher risk of adverse COVID-19, but risks are highest in the most disadvantaged, suggesting an additive influence between SES and lifestyle. COVID-19 policy and interventions should consider both lifestyle and SES. The greatest public health benefit from lifestyle focussed COVID-19 policy and interventions is likely to be seen when greatest support for healthy living is provided to the most disadvantaged groups.

Abstract Background Sarcopenia is defined as the loss of muscle mass and strength. Despite the seriousness of this disease, a single diagnostic criterion has not yet been established. Few studies have reported the prevalence of sarcopenia globally, and there is a high level of heterogeneity between studies, stemmed from the diagnostic criteria of sarcopenia and the target population. The aims of this systematic review and meta‐analysis were (i) to identify and summarize the diagnostic criteria used to define sarcopenia and severe sarcopenia and (ii) to estimate the global and region‐specific prevalence of sarcopenia and severe sarcopenia by sociodemographic factors. Methods Embase, MEDLINE, and Web of Science Core Collections were searched using relevant MeSH terms. The inclusion criteria were cross‐sectional or cohort studies in individuals aged ≥18 years, published in English, and with muscle mass measured using dual‐energy x‐ray absorptiometry, bioelectrical impedance, or computed tomography (CT) scan. For the meta‐analysis, studies were stratified by diagnostic criteria (classifications), cut‐off points, and instruments to assess muscle mass. If at least three studies reported the same classification, cut‐off points, and instrument to measure muscle mass, they were considered suitable for meta‐analysis. Following this approach, 6 classifications and 23 subgroups were created. Overall pooled estimates with inverse‐variance weights obtained from a random‐effects model were estimated using the metaprop command in Stata. Results Out of 19 320 studies, 263 were eligible for the narrative synthesis and 151 for meta‐analysis (total n = 692 056, mean age: 68.5 years). Using different classifications and cut‐off points, the prevalence of sarcopenia varied between 10% and 27% in the studies included for meta‐analysis. The highest and lowest prevalence were observed in Oceania and Europe using the European Working Group on Sarcopenia in Older People (EWGSOP) and EWGSOP2, respectively. The prevalence ranged from 8% to 36% in individuals

Abstract Background Reduced muscular strength, as measured by absolute grip strength, has been associated with increased risk of some site‐specific cancers. The ability of grip strength to predict other diseases may be affected by whether it is expressed in absolute or relative terms, but the evidence for cancer is scarce. This study compared the associations of absolute and relative grip strength with all‐cause and 15 site‐specific cancers. Methods A prospective cohort study was undertaken using data from the UK Biobank. The exposure variable was grip strength, in absolute form (kilogrammes) and relative to weight, body mass index (BMI), height. and body fat mass. The outcome was incident cancer, at 15 sites and overall. Cox proportional hazard models were performed to study the associations. Results This study included 445 552 participants, where 53.8% of the participants were women, with a mean (SD) age of 56.3 (8.11) years. During a median of 8.8 years follow‐up period, 48 886 (11.0%) patients were diagnosed with cancer. After adjusting for sociodemographic and lifestyle factors, as well as multiple testing, absolute grip strength was inversely and linearly associated with endometrial [hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.69; 0.79, P value

Abstract The graded association between family socioeconomic status (SES) and physical fitness is evident, but little is known about the mechanism underlying this association. This study investigated the role of early-life activities as mediators of the longitudinal relationship between early-life SES and health-related physical fitness in 168 adolescents (51.2% boys; final mean age: 12.4 years old). In Wave 1 (2011–12), their parents completed questionnaires about family socioeconomic status (SES), parent–child activities, and child screen time. In Wave 2 (2014–15), participants’ physical activity levels were assessed through parent proxy-reports. In Wave 3 (2018–19), a direct assessment of handgrip strength, standing long-jump, and 6-min walk test (6MWT) performance was conducted. After controlling for demographic factors, results of mediation analyses revealed that (a) Wave 1 SES predicted Wave 3 long-jump and 6MWT performance; (b) child physical activity level in Wave 2 mediated the relation between Wave 1 SES and standing long-jump performance in Wave 3; and (c) recreational parent–child activities and child screen time in wave 1 mediated the relation between Wave 1 SES and 6MWT performance in Wave 3. Our findings suggest that the type and frequency of early-life activities play a role in the graded association between childhood SES and physical fitness in adolescence.

IntroductionIn 2018, The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) published ten evidence-based Cancer Prevention Recommendations designed to reduce the risk of cancer via improved lifestyle behaviours. In 2019, Shams-White and colleagues created the “2018 WCRF/AICR Score” which aimed to standardise how adherence to these recommendations is assessed. The standardised scoring system includes seven of the recommendations concerning weight, physical activity and diet, with an optional eighth recommendation on breastfeeding. To promote transparency and reproducibility, the present paper describes the methodology for operationalisation of the standardised scoring system in the UK Biobank.MethodsUK Biobank recruited >500,000 individuals aged 37–73 years, between 2006 and 2010. In 2021, we held a workshop with experts which aimed to reach consensus on how to operationalise the scoring system using data available within UK Biobank. We used data on anthropometric measurements, physical activity and diet to calculate adherence scores. 24 h dietary assessment data were used to measure adherence to the following recommendations: “Eat a diet rich in wholegrains, vegetables, fruit, and beans”, “Limit consumption of “fast foods” and other processed foods high in fat, starches or sugars” and “Limit consumption of sugar-sweetened drinks”; food frequency questionnaire data were used to assess adherence to “Limit consumption of red and processed meat” and “Limit alcohol consumption”. Participants were allocated points for meeting, partially meeting or not meeting each recommendation, using cut-offs defined in the standardised scoring system.ResultsAt our workshop, discussions included the use of national guidelines to assess adherence to the recommendation on alcohol consumption, as well as challenges faced including defining the adapted ultra-processed food variables. A total score was calculated for 158,415 participants (mean 3.9 points, range 0–7 points). We also describe the methodology to derive a partial 5-point adherence score using data from the food frequency questionnaire in 314,616 participants.ConclusionWe describe the methodology used to estimate adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations for participants in the UK Biobank, including some of the challenges faced operationalising the standardised scoring system.

Abstract Background Growing evidence suggests that individuals with anxiety disorder have an elevated risk of cardiovascular disease (CVD) but few studies have assessed this association independently of or jointly with depression. Methods We conducted a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder, depression, and CVDs were ascertained through linked hospital admission and mortality data. Individual and joint associations between anxiety disorder and depression and CVD overall, as well as each of myocardial infarction, stroke/transient ischemic attack, and heart failure, were analyzed using Cox proportional hazard models and interaction tests. Results Among the 431,973 participants, the risk of CVD was higher among those who had been diagnosed with anxiety disorder only (hazard ratio [HR] 1.72; 95% confidence interval [CI] 1.32–2.24), depression only (HR 2.07; 95% CI 1.79–2.40), and both conditions (HR 2.89; 95% CI 2.03–4.11) compared to those without these conditions, respectively. There was very little evidence of multiplicative or additive interaction. Results were similar for myocardial infarction, stroke/transient ischemic attack, and heart failure. Conclusions Having anxiety is associated with the same magnitude of increased risk of CVD among people who do not have depression and those who do. Anxiety disorder should be considered for inclusion in CVD risk prediction and stratification, in addition to depression.

Abstract Aims Intimate partner violence (IPV) is a public health challenge negatively affecting victims’ health. Telomere length (TL), a marker for biological ageing, might be reflective of the mechanisms through which IPV leads to adverse health outcomes. The objective of the current study was to explore the association between IPV and leucocyte TL. Methods We conducted an analysis using a subset of the UK Biobank (N = 144 049). Physical, sexual and emotional IPV were reported by the participants. DNA was extracted from peripheral blood leukocytes. TL was assayed by quantitative polymerase chain reaction. We used multivariable linear regressions to test the associations between IPV and TL adjusted for age, sex, ethnicity, deprivation, education, as well as symptoms of depression and post-traumatic stress disorder in a sensitivity analysis. Results After adjusting for sociodemographic factors, any IPV was associated with 0.02-s.d. shorter TL (β = −0.02, 95% CI −0.04 to −0.01). Of the three types of IPV, physical violence had a marginally stronger association (β = −0.05, 95% CI −0.07 to −0.02) than the other two types. The associations of numbers of IPV and TL showed a dose–response pattern whereby those who experienced all three types of IPV types had the shortest TL (β = −0.07, 95% CI −0.12 to −0.03), followed by those who experienced two types (β = −0.04, 95% CI −0.07 to −0.01). Following additional adjustment for symptoms of depression and PTSD, the associations were slightly attenuated but the general trend by number of IPVs remained. Conclusions Victims of IPV, particularly those exposed to multiple types of IPVs, had shorter TL indicative of accelerated biological ageing. Given that all three types of IPV are linked to TL, clinical practitioners need to comprehensively identify all types of IPV and those who received multiple types. Further studies should explore the association of violence with changes in TL over time, as well as to which extent biological ageing is a mechanistic factor.

ObjectiveVitamin A deficiency (VAD) has serious public health consequences including morbidity and mortality for populations in low and middle-income countries (LMICs), especially for children under 5 years and pregnant women. LMICs are at greater risk of VAD, in part due to low levels of consumption of vitamin A-rich foods most of which are plant-based, such as orange-fleshed sweet potatoes (OFSP), with lower bioavailability than animal sources of the vitamin A. Food-based approaches such as biofortification of OFSP, including promoting the consumption of vitamin A-rich biofortified staple crops, has been shown to be potentially effective in improving the status of vitamin A and other micronutrients. This study examined vitamin A-rich food consumption and its predictors among women of reproductive age from OFSP-growing households in two regions of Uganda.MethodsA cross-sectional survey was conducted among 617 OFSP growing households, focusing on women in the reproductive age group from the northern and eastern regions of Uganda. Households were not receiving any VAD-related intervention at the time of the survey. Quantitative data included vitamin A-rich food consumption, knowledge on vitamin A, and rich food sources dietary intake, using a 7-day food frequency questionnaire. Vitamin A consumption and risk of deficiency were estimated using the Hellen Keller International guide.ResultsThe majority of women in this study were either pregnant (80%) or lactating (17%). More than 70% of the study population had a weighted vitamin A rich food consumption mean score of

Abstract Background Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer’s disease [AD] and vascular dementia) using the UK Biobank study. Methods 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. Results After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed

BackgroundThe aim of the current study was to determine the prevalence of low muscle strength and to evaluate physical activity and sleep characteristics in people with type 2 diabetes in Kuwait. Additionally, equivalent data from the UK Biobank cohort were compared.MethodsPeople with type 2 diabetes from the UK Biobank (n = 23,570) and Kuwaiti cohorts (n = 3,135) were included in this cross-sectional study. Self-reported sleep, physical activity, and muscle strength were compared between the cohorts, using linear and logistic regression, with adjustments for age, sex, and duration of diabetes.ResultsPhysical activity levels (−1216 (−1328,1104 Met-min/wee k: standardized B-coefficient −0.52 (−0.57, −0.47) and grip strength (−3.2 (−3.58, −2.82) kg: standardized B-coefficient (−0.29 (−0.32, -0.26) were lower in the Kuwaiti cohort and the odds of having short sleep (OR 1.32 (1.19,1.46), being classed as inactive (OR 8.70 (7.59, 9.98) and having muscle weakness were higher (OR 1.88 (1.69, 2.09). These analyses were adjusted for age, sex, and duration of diabetes.ConclusionsThis study demonstrates that insufficient sleep, physical inactivity, and muscle weakness are prevalent in people with type 2 diabetes, especially in Kuwait. Importantly, these observations warrant urgent and effective interventions to improve sleep, muscle strength, and physical activity, especially in Kuwait.

Abstract Background Sarcopenia often co‐occurs with osteoporosis in cross‐sectional studies. However, this association has rarely been studied in prospective studies. This study aimed to investigate the association between sarcopenia categories—along with its individual components—and incident osteoporosis in both middle‐aged and older men and women from the UK Biobank study. Methods A total of 168,682 participants (48.8% women, aged 37 to 70 years at baseline) were included in this prospective study. Categories of sarcopenia (pre‐sarcopenia and sarcopenia), and its individual components, were defined according to the EWGSOP2 criteria (2019). Associations with incident osteoporosis by sex were investigated using Cox‐proportional hazard models adjusted for socio‐demographic, lifestyle and health‐related factors, and morbidity count. Associations between categories of sarcopenia and incident osteoporosis were also investigated by age‐groups and subtype of osteoporosis (with and without pathological fractures). Results After a median follow‐up of 7.4 years, 6296 participants were diagnosed with osteoporosis. When the analyses were adjusted for a range of relevant confounding factors, pre‐sarcopenia was associated with 1.3‐times higher risk of osteoporosis in men (HR: 1.30 [95% CI: 1.03 to 1.63]) but not in women, and sarcopenia was associated with 1.66‐times increased osteoporosis risk in women (HR: 1.66 [95% CI: 1.33 to 2.08]) but not in men compared with people without sarcopenia or pre‐sarcopenia. A similar magnitude of associations was found in osteoporosis without pathological fractures but weaker for those with pathological fractures. Within the individual components, low muscle mass (HRwomen: 1.36 [95% CI: 1.22 to 1.51] and HRmen: 3.07 [95% CI: 1.68 to 5.59]), followed by slow gait speed (HRwomen: 1.30 [95% CI: 1.17 to 1.45] and HRmen: 1.70 [95% CI: 1.43 to 2.02]), were associated with a higher risk of incident osteoporosis in both sexes. Low grip strength was associated with a higher risk of incident osteoporosis in men (HR: 1.38 [95% CI: 1.15 to 1.65]), but not in women. No significant interaction between the exposures and incident osteoporosis by age groups were identified. Conclusions Our findings demonstrated that pre‐sarcopenic men and sarcopenic women had a higher risk of developing osteoporosis even after adjustment for a large range of potential confounders. Considering that sarcopenia could be prevented, health interventions to improve physical capability may delay or prevent the onset of osteoporosis.

Clinical time-to-event studies are dependent on large sample sizes, often not available at a single institution. However, this is countered by the fact that, particularly in the medical field, individual institutions are often legally unable to share their data, as medical data is subject to strong privacy protection due to its particular sensitivity. But the collection, and especially aggregation into centralized datasets, is also fraught with substantial legal risks and often outright unlawful. Existing solutions using federated learning have already demonstrated considerable potential as an alternative for central data collection. Unfortunately, current approaches are incomplete or not easily applicable in clinical studies owing to the complexity of federated infrastructures. This work presents privacy-aware and federated implementations of the most used time-to-event algorithms (survival curve, cumulative hazard rate, log-rank test, and Cox proportional hazards model) in clinical trials, based on a hybrid approach of federated learning, additive secret sharing, and differential privacy. On several benchmark datasets, we show that all algorithms produce highly similar, or in some cases, even identical results compared to traditional centralized time-to-event algorithms. Furthermore, we were able to reproduce the results of a previous clinical time-to-event study in various federated scenarios. All algorithms are accessible through the intuitive web-app Partea (https://partea.zbh.uni-hamburg.de), offering a graphical user interface for clinicians and non-computational researchers without programming knowledge. Partea removes the high infrastructural hurdles derived from existing federated learning approaches and removes the complexity of execution. Therefore, it is an easy-to-use alternative to central data collection, reducing bureaucratic efforts but also the legal risks associated with the processing of personal data to a minimum.

BackgroundInfection is associated with impaired nutritional status, especially for infants younger than 5 years.ObjectivesWe assessed the impact of infection indicated by both acute phase proteins (APP), C-reactive protein (CRP), and α-1-acid-glycoprotein (AGP), and as reported by maternal recall on the nutritional status of infants.Materials and methodsA total of 505 pregnant women were enrolled in a nested longitudinal cohort study of vitamin A (VA). Data from 385 children are reported here. The incidence and severity of respiratory infection and diarrhea (previous 14 days) were assessed by maternal recall; infant/child feeding practices were collected. Infant weight, recumbent length, and heel-prick capillary blood were taken at 9 months postpartum. Indicators of the VA status [retinol binding protein (RBP)], iron status (Hb, ferritin), and subclinical inflammation APP, CRP (>5 mg/L), and AGP (>1 g/L) were determined. Impacts of infection on the infant nutritional status were estimated using logistic regression models.ResultsInfection prevalence, based on elevated CRP and AGP levels, was 36.7%. For diarrhea reported symptoms, 42.4% of infants at 9 months had no indication of infection as indicated by CRP and AGP; for acute respiratory reported symptoms, 42.6% had no indication of infection. There was a significant positive association with infection among VA-deficient (RBP < 0.83 μmol/L) infants based on maternal reported symptoms but not with iron deficiency (ferritin < 12 μg/L). The odds of having infection, based on increased CRP and AGP, in underweight infants was 3.7 times higher (OR: 3.7; 95% CI: 2.3, 4.5; P = 0.019). Infants with iron deficiency were less likely (OR: 0.40; 95% CI: 0.1, 0.7; P = 0.001) to have infection based on CRP and AGP, while infants with VA deficiency were five times more likely (OR: 5.06; 95% CI: 3.2, 7.1; P = 0.0001) to have infection.ConclusionAcute phase proteins are more useful in defining infection in a population than reported symptoms of illness. Not controlling for inflammation in a population while assessing the nutritional status might result in inaccurate prevalence estimation.

The term “vegetarian” usually refers to individuals who exclude meat, fish, poultry and/or their derived products from their diet [...]

Abstract Background To evaluate the clinical management of choanal atresia (CA) in tertiary centers across Canada. Methods Multi-centre case series involving six tertiary care pediatric hospitals across Canada. Retrospective chart review of patients born between 1980 and 2010 diagnosed with choanal atresia to a participating center. Results The health charts of 215 patients (59.6% female) with choanal atresia (CA) were reviewed. Mean age of initial surgical repair was 0.8 months for bilateral CA, and 48.6 months for unilateral CA. Approaches of surgical repair consisted of endoscopic transnasal (31.7%), non-endoscopic transnasal (42.6%), and transpalatal (25.2%). Stents were used on 70.7% of patients. Forty-nine percent of patients were brought back to the OR for a planned second look; stent removal being the most common reason (86.4%). Surgical success rate of initial surgeries was 54.1%. Surgical technique was not associated with rate of restenosis [χ2 (2) = 1.6, p = .46]. Conclusions The present study is the first national multi-institutional study exploring the surgical outcomes of CA over a 30-year period. The surgical repair of CA presents a challenge to otolaryngologists, as the rate of surgical failure is high. The optimal surgical approach, age at surgical repair, use of stents, surgical adjuncts, and need for planned second look warrant further investigation. Graphical abstract

Abstract Background To evaluate the clinical presentation of choanal atresia (CA) in tertiary centers across Canada. Methods Multi-centre case series involving six tertiary care pediatric hospitals across Canada. Retrospective chart review of patients born between 1980 and 2010 diagnosed with CA at a participating center. Results The health charts of 215 patients (59.6% female) with CA were reviewed and included in this study. The mean age of patients at time of CA presentation was 0.4 months (range 0.1 to 7.2 months) for bilateral CA and 37.8 months (range 0.1 to 164.1 months) for unilateral cases. The most common presenting symptoms for bilateral CA in decreasing order were respiratory distress (96.4%), feeding difficulties (68.2%), and rhinorrhea (65.5%), and for unilateral cases in decreasing order were rhinorrhea (92.0%), feeding difficulties (24.7%), and respiratory distress (18.0%). For the majority of patients (73.2%), the obstruction comprised mixed bony and membranous tissue, with only 10.5% presenting with a purely membranous obstruction. Familial history of CA was confirmed in only 3.3% of cases. One half of patients with CA presented with one or more associated anomalies and 30.6% had a syndrome. Conclusions The present investigation is the first national multi-institutional study evaluating the clinical presentation of CA over three decades. The present cohort of CA patients presented with a breadth of co-morbidities with highly variable presentations, with bilateral cases being more severely affected than unilateral cases. Further investigation into hereditary linkages to CA development is warranted. Graphical abstract