Different Sources of Fiber Intake and Risk of 17 Specific Cancers and All Cancers Combined: Prospective Study of 364,856 Participants in the UK Biobank.

Inverse associations between dietary fiber (DF) and colorectal cancer risk are well-established. However, evidence is limited in relation to other cancer sites. This study, of 364,856 participants from the UK Biobank, aimed to evaluate the associations between total and source-specific partial DF and risk of 17 specific cancers and all cancers combined. Partial DF was derived from baseline touchscreen questionnaire data on cereal, bread, fruit, and vegetable intake. The outcomes were incident cancer at 17 sites and all cancers combined. Cox proportional hazards models were applied. Over a median 8.8-year follow-up period, 30,725 people were diagnosed with cancer. After adjusting for sociodemographic and lifestyle factors, those in the highest quintile of partial DF compared with the lowest quintile (<9.6 vs ≥19.1 g/day) had 10% lower risk of cancer overall, with the greatest risk reductions observed for cervical (hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.14; 0.82), esophageal (HR = 0.66, 95% CI: 0.52; 0.84), lung (HR = 0.67, 95% CI: 0.59; 0.76), bladder (HR = 0.72, 95% CI: 0.56; 0.91), and kidney (HR = 0.75, 95% CI: 0.61; 0.92) cancers. Associations between DF and lung cancer were observed only in current and former smokers. Higher DF intake, in particular cereal fiber and fruit and vegetable fiber, was associated with a lower risk of overall and multiple site-specific cancers.

How do lifestyle factors modify the association between genetic predisposition and obesity-related phenotypes? A 4-way decomposition analysis using UK Biobank.

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.

Weight velocity in addition to latest weight does not improve the identification of wasting, or the prediction of stunting and mortality: a longitudinal analysis using data from Malawi, South Africa, and Pakistan.

BACKGROUND: In low/middle-income countries, most nutritional assessments use the latest weights, without reference to growth trajectory. OBJECTIVE: This study explores whether velocity, in addition to the latest weight, improves the prediction of wasting, stunting or mortality in the first two years of life. METHODS: We analysed a combined data set with weight and height data collected monthly in the first year of 3447 children from Pakistan, Malawi, South Africa, with height and survival recorded till 24 months. The main exposures were weight-for-age z-score (WAZ) at the end of each 2-month period and weight velocity-for-age z-score (WVZ2) across that period. The outcomes were wasting, stunting or all-cause mortality in the next 1-2 months. As a sensitivity analysis, we also used WVZ over 6 months (WVZ6), with matching WAZ. Cox proportional hazard models with repeated growth measures were used to study the association between exposures and mortality. Mixed Poisson models were used for stunting and wasting. RESULTS: Children who were already stunted or wasted were most likely to remain so. WVZ2 was associated with a lower risk of subsequent stunting (RR 0.95; 95% CI 0.93-0.96), but added minimal prediction (difference in AUC = 0.004) compared to a model including only WAZ. Similarly, WVZ2 was associated with wasting (RR 0.74; 95% CI 0.72-0.76) but the prediction was only marginally greater than for WAZ (difference in AUC = 0.015). Compared to WAZ, WVZ6 was less predictive for both wasting and stunting. Low WVZ6 (but not WVZ2) was associated with increased mortality (HR 0.75, 95% CI 0.67-0.85), but added marginal only prediction to a model including WAZ alone (difference in C = 0.015). CONCLUSIONS: The key anthropometric determinant of impending wasting, stunting, and mortality appears to be how far below the normal range the child's weight is, rather than how they reached that position.

In people with type 2 diabetes, sarcopenia is associated with the incidence of cardiovascular disease: A prospective cohort study from the UK Biobank.

AIM: To investigate the association of sarcopenia with cardiovascular disease (CVD) incidence in people with type 2 diabetes. MATERIALS AND METHODS: A prospective cohort study with 11 974 White European UK Biobank participants with type 2 diabetes, aged 40-70 years, included. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People as either non-sarcopenic or sarcopenic. Outcomes included CVD, stroke, heart failure (HF) and myocardial infarction (MI). The association between sarcopenia and the incidence of outcomes was investigated using Cox proportional hazard models adjusted for sociodemographic and lifestyle factors. The rate advancement period was used to estimate the time period by which CVD is advanced because of sarcopenia. RESULTS: Over a median follow-up of 10.7 years, 1957 participants developed CVDs: 373 had a stroke, 307 had an MI and 742 developed HF. Compared with non-sarcopenia, those with sarcopenia had higher risks of CVD (HR 1.89 [95% CI 1.61; 2.21]), HF (HR 2.59 [95% CI 2.12; 3.18]), stroke (HR 1.90 [95% CI 1.38; 2.63]), and MI (HR 1.56 [95% CI 1.04; 2.33]) after adjustment for all covariates. Those with sarcopenia had CVD incidence rates equivalent to those without sarcopenia who were 14.5 years older. Similar results were found for stroke, HF and MI. CONCLUSIONS: In people with type 2 diabetes, sarcopenia increased the risk of developing CVD, which might occur earlier than in those without sarcopenia. Therefore, sarcopenia screening and prevention in patients with type 2 diabetes may be useful to prevent the complications of CVD.

Association of five diet scores with severe NAFLD incidence: A prospective study from UK Biobank.

AIM: This study aimed to contrast the associations of five common diet scores with severe non-alcoholic fatty liver disease (NAFLD) incidence. MATERIALS AND METHODS: In total, 162 999 UK Biobank participants were included in this prospective population-based study. Five international diet scores were included: the 14-Item Mediterranean Diet Adherence Screener (MEDAS-14), the Recommended Food Score (RFS), the Healthy Diet Indicator (HDI), the Mediterranean Diet Score and the Mediterranean-DASH Intervention for Neurodegenerative Delay score. As each score has different measurements and scales, all scores were standardized and categorized into quartiles. Cox proportional hazard models adjusted for confounder factors investigated associations between the standardized quartiles and severe NAFLD incidence. RESULTS: Over a median follow-up of 10.2 years, 1370 participants were diagnosed with severe NAFLD. When the analyses were fully adjusted, participants in quartile 4 using the MEDAS-14 and RFS scores, as well as those in quartiles 2 and 3 using the HDI score, had a significantly lower risk of severe incident NAFLD compared with those in quartile 1. The lowest risk was observed in quartile 4 for the MEDAS-14 score [hazard ratio (HR): 0.76 (95% confidence interval (CI): 0.62-0.94)] and the RFS score [HR: 0.82 (95% CI: 0.69-0.96)] and as well as in quartile 2 in the HDI score [HR: 0.80 (95% CI: 0.70-0.91)]. CONCLUSION: MEDAS-14, RFS and HDI scores were the strongest diet score predictors of severe NAFLD. A healthy diet might protect against NAFLD development irrespective of the specific approach used to assess diet. However, following these score recommendations could represent optimal dietary approaches to mitigate NAFLD risk.

Association between birth weight and insulin resistance in US adolescents: A retrospective cohort study exploring the role of concurrent body mass index.

BACKGROUND AND AIMS: This study aimed to investigate the association between birth weight (BW) and abnormal HOMA-IR in US adolescents aged 12-15 years. The role of concurrent body mass index (BMI) in adolescence was also examined. METHODS AND RESULTS: This retrospective cohort study included 3429 participants from NHANES with data in 1999-2020. HOMA-IR ≥2.3 was considered abnormal. Participants were classified as low (LBW; <2.5 kg), normal (NBW; 2.5-4.0 kg), or high (HBW; >4.0 kg) BW. Logistic regression was used to explore the association between BW and HOMA-IR. Mediation analysis was used to examine whether BMI z-score in adolescence mediated the association between BW and HOMA-IR. Compared with those in NBW, the odds ratios (95 % CI) of abnormal HOMA-IR in LBW and HBW groups were 1.26 (0.99-1.60), and 0.62 (0.47-0.83) respectively. The association between BW and abnormal HOMA-IR was consistent in all subgroups with no significant interactions. Mediation analysis showed that BW is associated with lower risk of HOMA-IR directly, but with higher risk indirectly via BMI in adolescence. CONCLUSION: There was a negative linear relationship between BW and the prevalence of abnormal HOMA-IR in adolescents aged 12-15 independent of concurrent BMI. Children who were born with LBW but had high BMI in adolescence were of particularly higher risk of insulin resistance.

Socio-demographic variation in adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations within the UK Biobank prospective cohort study.

BACKGROUND: The 2018 (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are evidence-based lifestyle recommendations which aim to reduce the risk of cancer worldwide. Sociodemographic factors modulate lifestyle behaviours, and both cancer incidence and survival are socio-economically patterned. We investigated adherence to these recommendations and examined patterns of adherence across sociodemographic subgroups in the UK Biobank cohort. METHODS: We included 158 415 UK Biobank participants (mean age 56 years, 53% female). Total adherence scores were derived from dietary, physical activity and anthropometric data using the 2018 WCRF/AICR standardized scoring system. One-Way analysis of variance (ANOVA) was used to test for differences in total scores and in values for individual score components according to sociodemographic factors and Pearson's Χ2 test to investigate associations between sociodemographic factors according to tertiles of adherence score. RESULTS: Mean total adherence score was 3.85 points (SD 1.05, range 0-7 points). Higher total scores were observed in females, and older (>57 years), Chinese or South Asian, and more educated participants. We found significant variations in adherence to individual recommendations by sociodemographic factors including education, Townsend deprivation index and ethnicity. CONCLUSIONS: Identifying and understanding lifestyle and dietary patterns according to sociodemographic factors could help to guide public health strategies for the prevention of cancers and other non-communicable diseases.

The impact of COVID-19 and associated lockdowns on traumatic spinal cord injury incidence: a population based study.

STUDY DESIGN: Natural experiment OBJECTIVES: To determine whether COVID-19 restrictions were associated with changes in the incidence of traumatic spinal cord injury (TSCI) in Scotland. SETTING: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole provider of treatment for TSCI in Scotland. METHODS: Time series analysis of all admissions for TSCI between 1st January 2015 and 31st August 2022. RESULTS: Over the 8-year study period, 745 patients were admitted to the QENSIU with a TSCI. Interrupted time series analysis showed that level 3 and 4 COVID-19 lockdown restrictions (the most severe levels) were associated with lower incidence of TSCI (RR 0.63, CI% CI 0.47, 0.82, p < 0.001). The associations were stronger in people aged over 45 (additive interaction p = 0.001), males (additive interaction p = 0.01) and non-tetraplegia (additive interaction p = 0.002). The incidence of TSCI due to deliberate self-harm was higher (0.41 versus 0.23 per month) during restrictions. CONCLUSIONS: Overall, TSCI incidence reduced in Scotland when lockdowns were implemented, presumably due to lower engagement in risky activities. The increase in TSCI due to deliberate self-harm may reflect increased mental health problems and social isolation and should be anticipated and targeted in future pandemics. The change in incidence during the COVID-19 pandemic may have an economic impact and see a temporary reduction in the burden on health and social care. The results of this study will be useful for resource planning in future pandemics.

Effect of a Mobile Game-Based Intervention to Enhance Child Safety: Randomized Controlled Trial.

BACKGROUND: Evidence 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. OBJECTIVE: This study aimed to investigate the potential of a mobile game-based safety education program in improving children's safety and psychosocial outcomes. METHODS: Safe 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. RESULTS: No 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. CONCLUSIONS: Analysis 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 REGISTRATION: ClinicalTrials.org NCT04096196; https://clinicaltrials.gov/show/NCT04096196. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/17756.

Association Between Device-Measured Physical Activity and Incident Heart Failure: A Prospective Cohort Study of 94 739 UK Biobank Participants.

BACKGROUND: Studies of objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not heart failure (HF), an emerging chronic condition. This study aimed to investigate the dose-response relationship between device-measured PA and HF by intensity of PA. METHODS: This was a prospective cohort study of 94 739 UK Biobank participants who had device-measured PA in 2013 to 2015 and were free from myocardial infarction and HF. PA was measured with a wrist-worn accelerometer, and time spent on light-, moderate-, and vigorous-intensity PA was extracted. Incident HF was ascertained from linked hospital and death records. Cox proportional hazard models with cubic penalized splines were used to study the associations, which were adjusted for sociodemographic and lifestyle factors. Competing risk was handled with cause-specific hazard ratios. RESULTS: The overall incidence of HF was 98.5 per 10 000 person-years over a median 6.1 years of follow-up. Compared with participants who undertook no moderate- to vigorous-intensity PA, those who performed 150 to 300 min/wk of moderate-intensity PA (hazard ratio, 0.37 [95% CI, 0.34-0.41]) and 75 to 150 min/wk of vigorous-intensity PA (hazard ratio, 0.34 [95% CI, 0.25-0.46]) were at lower HF risk. The association between vigorous-intensity PA and HF was reverse-J shaped with a potentially lower risk reduction above 150 min/wk. CONCLUSIONS: Device-measured PA, especially moderate-intensity PA, was associated with a lower risk of HF. Current vigorous-intensity PA recommendations should be encouraged but not increased. In contrast, increasing moderate-intensity PA may be beneficial even among those meeting current recommendations.

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and cancer risk: A systematic review and meta-analysis.

BACKGROUND: The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A systematic review and meta-analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted. METHODS: MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta-analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1-point increment) and categorical (highest vs. lowest score category) variable using random-effects models were estimated. RESULTS: Eighteen studies (11 cohort; seven case-control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1-point increment in adherence score was 0.89 (95% CI, 0.85-0.93; I2  = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84-0.91; I2  = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86-0.98, I2  = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta-analysis results using categorical adherence score variables were consistent with these findings. CONCLUSIONS: Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted. PROSPERO REGISTRATION NUMBER: CRD42022313327.

Association between menstrual cycle phase and metabolites in healthy, regularly menstruating women in UK Biobank, and effect modification by inflammatory markers and risk factors for metabolic disease.

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 < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively. CONCLUSIONS: Cholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women.

Adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations and risk of 14 lifestyle-related cancers in the UK Biobank prospective cohort study.

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.

Dose-response relationship between device-measured physical activity and incident type 2 diabetes: findings from the UK Biobank prospective cohort study.

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 < 150 min/week of moderate PA, people achieving 150-300, 300-600 and > 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 < 25 min/week, individuals achieving 25-50, 50-75 and > 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).

Associations between an inflammatory diet index and severe non-alcoholic fatty liver disease: a prospective study of 171,544 UK Biobank participants.

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], neutral [E-DII - 1 to 1] and very/moderately pro-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.

Child maltreatment and telomere length in middle and older age: retrospective cohort study of 141 748 UK Biobank participants.

BACKGROUND: There is evidence that child maltreatment is associated with shorter telomere length in early life. AIMS: This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults. METHOD: This was a retrospective cohort study of 141 748 UK Biobank participants aged 37-73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association. RESULTS: After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths (ß = -0.05, 95% CI -0.07 to -0.03; P < 0.0001), followed by those with two types of maltreatment (ß = -0.02, 95% CI -0.04 to 0.00; P = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter (ß = -0.04, 95% CI -0.07 to -0.02; P = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse (ß = -0.05, 95% CI -0.07 to -0.03; P < 0.0001) and sexual abuse (ß = -0.02, 95% CI -0.04 to 0.00; P = 0.02) were independently associated with shorter telomere length. CONCLUSIONS: Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.

Association between walking pace and incident type 2 diabetes by adiposity level: A prospective cohort study from the UK Biobank.

AIMS: To investigate the combined association of adiposity and walking pace with incident type 2 diabetes. METHODS: We undertook a prospective cohort study in 194 304 White-European participants (mean age 56.5 years, 55.9% women). Participants' walking pace was self-reported as brisk, average or slow. Adiposity measures included body mass index (BMI), waist circumference (WC) and body fat percentage (BF%). Associations were investigated using Cox proportional hazard models, with a 2-year landmark analysis. A four-way decomposition analysis was used for mediation and additive interaction. RESULTS: The median (interquartile range) follow-up was 5.4 (4.8-6.3) years. During the follow-up period, 4564 participants developed type 2 diabetes. Compared to brisk-walking participants with normal BMI, those with obesity who walked briskly were at an approximately 10- to 12-fold higher risk of type 2 diabetes (hazard ratio [HR] 9.64, 95% confidence interval [CI] 7.24-12.84, in women; HR 11.91, 95% CI 8.80-16.12, in men), whereas those with obesity and walked slowly had an approximately 12- to 15-fold higher risk (HR 12.68, 95% CI 9.62-16.71, in women; HR 15.41, 95% CI 11.27-21.06, in men). There was evidence of an additive interaction between WC and BF% and walking pace among women, explaining 17.8% and 47.9% excess risk respectively. Obesity mediated the association in women and men, accounting for 60.1% and 44.9%, respectively. CONCLUSIONS: Slow walking pace is a risk factor for type 2 diabetes independent of adiposity. Promoting brisk walking as well as weight management might be an effective type 2 diabetes prevention strategy given their synergistic effects.

Preterm postnatal complications and risk of attention-deficit/hyperactivity disorder.

AIM: To investigate the association between the risk of attention-deficit/hyperactivity disorder (ADHD) and preterm birth and determine how postnatal complications in children born preterm is associated with the risk of ADHD. METHOD: This population-based cohort study used data from the Hong Kong electronic medical records. We followed 359 614 children (48% female; 6-17 years old, mean 11 years 7 months, SD 3 years 2 months) born in public hospitals in Hong Kong from 1st January 2004 to 31st December 2014 and collected medical records and demographic details for mothers and children until 11th November 2020. RESULTS: The risk of ADHD was 4.0% in children born at term and 5.1% in children born preterm. The odds ratio for ADHD was 2.08 (95% confidence interval [CI] 1.64-2.64) for children born extremely preterm, 1.64 (95% CI 1.46-1.85) for children born very preterm, and 1.15 (95% CI 1.08-1.23) for children born late preterm. Among preterm postnatal complications, only early respiratory disease, retinopathy of prematurity (ROP), and intraventricular haemorrhage were significant predictors of ADHD after controlling for preterm birth, other risk factors, and sociodemographic variables. The excess risk of ADHD among children born very preterm or late preterm could be partly explained by respiratory disease. ROP partially mediated the risk of ADHD in children born very preterm. INTERPRETATION: Children born preterm in all subcategories, from extremely preterm to late preterm, have increased risk of ADHD. Early respiratory infection partially mediates the risk of ADHD in children born preterm.

Associations of grip strength and walking pace with mortality in stroke survivors: A prospective study from UK Biobank.

INTRODUCTION: Although stroke is an emerging cause of disability and mortality globally, associations between physical capability markers and mortality in stroke survivors are elusive. This study investigated the individual and combined associations of walking pace and grip strength with all-cause and stroke mortality in stroke survivors. METHODS: Individual and combined associations of walking pace and grip strength with stroke deaths and all-cause mortality were investigated using Cox proportional-hazard models adjusted for sociodemographic, lifestyle, and health-related variables. RESULTS: Seven thousand four hundred eighty-six stroke survivors from the UK Biobank study (aged 40-70 years; 42.4% women) were included in this prospective study. Over a median follow-up of 12.6 (IQR: 11.9-13.3) years, 1490 (19.9%) participants died, of whom 222 (3.0%) died from stroke. After adjusting for confounding factors, and compared to individuals in the average/brisk walking pace category, those who reported a slow walking pace had 2.00 (95% CI: 1.50-2.68) and 1.99 (95% CI: 1.78-2.23) times higher risk of stroke mortality and all-cause mortality, respectively. Similar associations were identified for participants with low grip strength compared with those with normal levels. For combined associations, those with both slow walking pace and low grip strength showed the highest risk of stroke mortality (hazard ratio: 2.86 [95% CI: 1.93-4.22]). Similar results were found for all-cause mortality. CONCLUSIONS: Low grip strength and slow walking pace were associated with a higher risk of stroke and all-cause mortality in stroke survivors. If these associations are causal, improving physical capability among stroke survivors might potentially prolong survival.

Association between being breastfed and cardiovascular disease: a population cohort study of 320 249 participants.

BACKGROUND: Being breastfed is associated with lower cardiovascular risk factors but, to date, no studies have demonstrated a protective effect on cardiovascular disease (CVD). This study aims to address the limitations of previous studies, specifically insufficient statistical power and residual confounding, to determine if such association exists. METHODS: This is a population-based retrospective cohort study of 320 249 men and women aged 40-69 years. Breastfeeding status was self-reported. CVD and myocardial infarction (MI) events and deaths based via linkage to hospitalization and death records. RESULTS: Overall, 28 469 (8.4%) participants experienced a CVD event and 5174 (1.6%) experienced an MI. Following adjustment for sociodemographic, lifestyle and early life confounders, breastfeeding was associated with a reduced risk of CVD events (HR 0.97, 95% CI 0.94-1.00, P = 0.041), CVD deaths (HR 0.91, 95% CI 0.84-0.98, P = 0.017), MI events (HR 0.93, 95% CI 0.87-0.99, P = 0.033) and MI deaths (HR 0.81, 95% CI 0.67-0.98, P = 0.026). CONCLUSIONS: Child health benefits of breastfeeding are well established. However, the benefits of breastfeeding may extend into later life reinforcing the need to encourage and support breastfeeding.