Associations between modifiable risk factors and hepatocellular carcinoma: a trans-ancestry Mendelian randomization study.

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear. METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations. RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results. CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.

Associations between modifiable risk factors and frailty progression among individuals with pre-frailty.

BACKGROUND: In the context of the present global aging phenomenon, the senior population and pace of aging in China have emerged as prominent issues on the worldwide stage. Frailty, a complicated condition that is closely linked to the clinical syndrome of advancing age, poses a considerable health risk to older individuals. Frailty status was assessed by the frailty index (FI) ranging from 0 to 1, pre-frailty was defined as >0.10 to <0.25, and frailty was defined as ≥0.25. To look at the connection between modifiable risk factors and frailty progression among individuals in the pre-frailty population. METHODS: Using pre-frailty patients as characterized by the 32-frailty index, the study focused on middle-aged and elderly persons from China and ultimately recruited 5,411 participants for analysis. The relationship between modifiable factors and changes in pre-frailty status throughout follow-up was investigated. Modifiable factors were body mass index (BMI), abdominal obesity, smoking status, alcohol use, and sleep status. We employed logistic regression to examine the relationships between modifiable risk factors and changes in pre-frailty status, as well as the associations between modifiable factors scores and the corresponding pre-frailty progression. Additionally, we generated the modifiable factors scores and examined how these related to modifications in the pre-frailty stage. RESULTS: In this study, after a mean follow-up of 6 years, (OR = 0.59, 95%CI: 0.48-0.71) for BMI ≥ 25 kg/m2 and (OR = 0.74, 95%CI: 0.63-0.89) for concomitant abdominal obesity were significantly associated with lower reversal to a healthy state; (OR = 1.24, 95%CI:1.07-1.44) and (OR = 1.25, 95%CI: 1.10-1.42) for the group that negatively progressed further to frailty were significantly associated with increased frailty progression profile. Subsequently, investigation of modifiable factor scores and changes of pre-frailty status found that as scores increased further, frailty developed (OR = 1.12, 95%CI:1.05-1.18), with scores of 3 and 4 of (OR = 1.38, 95%CI: 1.08-1.77) and (OR = 1.52, 95%CI:1.09-2.14). Finally, we also performed a series of stratified analyses and found that rural unmarried men aged 45 to 60 years with less than a high school degree were more likely to develop a frailty state once they developed abdominal obesity. CONCLUSION: In pre-frailty individuals, maintaining more favorable controllable variables considerably enhances the chance of return to normal and, conversely, increase the risk of progressing to the frailty.

Associations Between Estimated Pulse Wave Velocity and Five-Year All-Cause Mortality in Patients with Atherosclerotic Cardiovascular Disease with and without Standard Modifiable Risk Factors: Evidence From NHANES 1999-2016.

Aim: The study aimed to analyze the associations between estimated pulse wave velocity (ePWV) and 5-year mortality in atherosclerotic cardiovascular disease (ASCVD) patients with and without standard modifiable risk factors (SMuRFs), which included smoking status, hypertension, diabetes, and hypercholesterolemia. Methods: The present retrospective cohort study utilized data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016. Patients with ASCVD who completed both the questionnaire survey and serum testing were included. Patients were categorized into the ≥1 SMuRF group if they had at least one SMuRF, while those without any SMuRFs were classified into the SMuRF-less group. The ePWV, which was calculated using the age and mean blood pressure, was evenly divided into three categories: low (Q1), medium (Q2), and high (Q3). Multivariable weighted Cox proportional-hazard regression analyses were utilized to explore the risk factors associated with 5-year mortality in patients with and without SMuRFs. And restricted cubic spline curve (RCS) was used to assess their nonlinear correlation. Results: A total of 1901 patients with ASCVD were included in the study. For the patients in ≥1 SMuRF group, the Q3 group included patients who were older, with a higher proportion of males, more comorbidities, and a lower body mass index than the Q1 group (P<0.05). The Cox proportional-hazard regression model results revealed, the Q3 group had a higher risk of 5-year mortality than the Q1 group [hazard ratio (HR) 4.30, 95% confidence interval (CI) (2.66, 6.95), P<0.001]. RCS demonstrated a linear trend between high level of ePWV and decreased risks of mortality. Similar results were observed in the SMuRF-less group [HR 10.62, 95% CI (1.22, 92.06), P=0.032]. Conclusion: A high level of ePWV signified a higher risk of 5-year mortality in ASCVD patients with and without SMuRFs.

Poor sleep quality is an important modifiable risk factor for dementia: Population attributable fraction of poor sleep in a Brazilian population-based study.

OBJECTIVES: The populational impact of poor sleep quality and the risk of dementia is unclear. We analyzed the Population Attributable Fraction (PAF) of poor sleep quality for dementia, and its association with other two sleep parameters through self-reported and single questions collected in a large-scale Brazilian cohort (ELSI-Brazil). METHODS: A subset of the ELSI-Brazil with complete responses to sleep quality was retrieved for this study. This is a large representative sample of the Brazilian elderly population with an extensive assessment of sociodemographic and health risk variables. Prevalence of poor sleep quality was estimated according to the complex sample design, and its PAF was measured using a meta-analytic relative risk. A total of 6024 (56.3% women, mean 62.8 ± 9.5 years of age) individuals had complete responses. RESULTS: The prevalence of poor sleep quality was 24.9% (95%CI 23%-26%), and the PAF of poor sleep quality including other 10 modifiable risk factors of dementia was 52.5% in Brazil. Secondary analyses identified that sleep quality, restorative sleep and sleep drug usage varied considerably according to age ranges, race, and gender. CONCLUSIONS: Poor sleep quality is an important populational modifiable risk factor for dementia in Brazil. Targeted interventions may provide an important impact in preventing dementia in low- and middle-income countries.

AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests.

PURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies. METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes. RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl ß-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence. CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.

Modifiable risk factors for cancer among people with lynch syndrome: an international, cross-sectional survey.

BACKGROUND: Lynch syndrome is the most common cause of hereditary colorectal and endometrial cancer. Lifestyle modification may provide an opportunity for adjunctive cancer prevention. In this study, we aimed to characterise modifiable risk factors in people with Lynch syndrome and compare this with international guidelines for cancer prevention. METHODS: A cross-sectional study was carried out utilizing survey methodology. Following public and patient involvement, the survey was disseminated through patient advocacy groups and by social media. Self-reported demographic and health behaviours were collected in April 2023. Guidelines from the World Cancer Research Fund (WCRF) were used to compare percentage adherence to 9 lifestyle recommendations, including diet, physical activity, weight, and alcohol intake. Median adherence scores, as a surrogate for lifestyle risk, were calculated and compared between groups. RESULTS: 156 individuals with Lynch syndrome participated from 13 countries. The median age was 51, and 54% were cancer survivors. The mean BMI was 26.7 and the mean weekly duration of moderate to vigorous physical activity was 90 min. Median weekly consumption of ethanol was 60 g, and 3% reported current smoking. Adherence to WCRF recommendations for cancer prevention ranged from 9 to 73%, with all but one recommendation having < 50% adherence. The median adherence score was 2.5 out of 7. There was no significant association between median adherence scores and age (p = 0.27), sex (p = 0.31), or cancer history (p = 0.75). CONCLUSIONS: We have characterised the modifiable risk profile of people living with Lynch syndrome, outlining targets for intervention based on lifestyle guidelines for the general population. As evidence supporting the relevance of modifiable factors in Lynch syndrome emerges, behavioural modification may prove an impactful means of cancer prevention.

Perception of Perioperative Risk for Arthroplasty Patients: A Poll of Chinese Orthopaedic Surgeons.

BACKGROUND: Informed by the precedent of an American Association of Hip and Knee Surgeons (AAHKS) survey, where 95% of participants reported instigating modifications to preoperative risk factors, this study appraised the approach of Chinese arthroplasty surgeons toward patients who had modifiable risks. METHODS: An adaptation of the AAHKS survey tool for a Chinese cohort was undertaken. The survey queried 600 Chinese Society of Hip and Knee Surgeons members on whether the perception of unoptimized medical comorbidities and socioeconomic elements affects the propensity to offer surgical procedures. RESULTS: Out of the distributed surveys, 150 responses were received, culminating in a response rate of 25%. The data illustrate that 98.7% of Chinese surgeons practice restrictions on arthroplasty access for patients who have modifiable risk factors, with notable frequencies for malnutrition (93.3%), anemia (91.3%), recent hyaluronic acid injections (within one month, 88.7%), and corticosteroid injections (within 3 months, 74.7%). Assessment criteria ahead of surgery included limitations such as a body mass index under 40 (47.3%), requirements for smoking cessation (57.3%), an acceptable hemoglobin A1c level (95.3%), and a dependent fasting blood glucose level (88%). Moreover, 87.3% of respondents endorsed the need for additional interventions for certain socioeconomically disadvantaged patients to achieve successful outcomes. A majority of respondents (94.7%) believed that more equitable access to care, facilitated by better-adjusted payment methodologies, could enhance patient outcomes. Current payment schemes were also perceived by a majority to potentially compromise outcomes for patients who have inadequate social support (80.7%), low socioeconomic status (67.3%), and those lacking insurance (72.7%). CONCLUSIONS: The consistency of the almost 99% response rate in addressing modifiable risk factors prior to arthroplasty aligns closely with the reported practices in the AAHKS survey. These findings underscore the shared valuation of preoperative risk factor optimization by Chinese and American arthroplasty surgeons, notwithstanding divergent healthcare system structures.

Effectiveness of pedometer-based walking programmes in improving some modifiable risk factors of stroke among community-dwelling older adults: a systematic review, theoretical synthesis and meta-analysis.

BACKGROUND: Pedometer-based walking programs hold promise as a health promotion strategy for stroke prevention in community-dwelling older adults, particularly when targeted at physical activity-related modifiable risk factors. The question arises: What is the effectiveness of pedometer-based walking program interventions in improving modifiable stroke risk factors among community-dwelling older adults? METHOD: Eight databases were searched up to December 2nd, 2023, following the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol. Inclusion criteria focused on randomized controlled trials (RCTS) involving community-dwelling older adults and reported in English. Two independent reviewers utilized Physiotherapy Evidence Database (PEDro) tool to extract data, assess eligibility, evaluate study quality, and identify potential bias. Standardized mean difference (SMD) was employed as summary statistics for primary -physical activity level -and secondary outcomes related to cardiovascular function (blood pressure) and metabolic syndrome, including obesity (measured by body mass index and waist circumference), fasting blood sugar, glycated hemoglobin, high-density lipoprotein cholesterol (HDL-C), and triglycerides. A random-effects model was used to generate summary estimates of effects. RESULTS: The review analyzed eight studies involving 1546 participants aged 60-85 years, with 1348 successfully completing the studies. Across these studies, pedometer-based walking programs were implemented 2-3 times per week, with sessions lasting 40-60 minutes, over a duration of 4-26 weeks. The risk of bias varied from high to moderate. Our narrative synthesis revealed positive trends in HDL-C levels, fasting blood sugar, and glycated hemoglobin, suggesting improved glycemic control and long-term blood sugar management. However, the impact on triglycerides was only marginal. Primary meta-analysis demonstrated significantly improved physical activity behavior (SMD=0.44,95%CI:0.26, 0.61,p=<0.00001;I2=0%;4 studies; 532 participants) and systolic blood pressure (SMD=-0.34,95%CI:-0.59,-0.09;p=<0.008;I2=65%,2 studies;249 participants), unlike diastolic blood pressure (SMD=0.13,95%CI:-0.13,-0.38,p=0.33; I2=91%; 2 studies; 237 participants). Interventions based on social cognitive, self-efficacy, and self-efficiency theory(ies), and social cognitive theory applied in an ecological framework, were linked to successful physical activity behavior outcomes. CONCLUSION: Pedometer-based walking programs, utilizing interpersonal health behavior theory/ecological framework, enhance physical activity behavior and have antihypertensive effects in community-dwelling older adults. While they do not significantly affect diastolic blood pressure, these programs potentially serve as a primary stroke prevention strategy aligning with global health goals. TRIAL REGISTRATION: Registration Number: INPLASY202230118.

Aging and cancer.

Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis that aging and cancer coincide because both are driven by time, irrespective of the precise causes, can be confronted with the idea that aging and cancer share common mechanistic grounds that are referred to as 'hallmarks'. Indeed, several hallmarks of aging also contribute to carcinogenesis and tumor progression, but some of the molecular and cellular characteristics of aging may also reduce the probability of developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied by a reduced incidence of neoplastic diseases. We will also discuss the possibility that the aging process itself causes cancer, meaning that the time-dependent degradation of cellular and supracellular functions that accompanies aging produces cancer as a byproduct or 'age-associated disease'. Conversely, cancer and its treatment may erode health and drive the aging process, as this has dramatically been documented for cancer survivors diagnosed during childhood, adolescence, and young adulthood. We conclude that aging and cancer are connected by common superior causes including endogenous and lifestyle factors, as well as by a bidirectional crosstalk, that together render old age not only a risk factor of cancer but also an important parameter that must be considered for therapeutic decisions.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). CONCLUSIONS: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

Association of LIfestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline.

INTRODUCTION: Evaluating whether genetic susceptibility modifies the impact of lifestyle-related factors on dementia is critical for prevention. METHODS: We studied 5170 participants from a French cohort of older persons free of dementia at baseline and followed for up to 17 years. The LIfestyle for BRAin health risk score (LIBRA) including 12 modifiable factors was constructed at baseline (higher score indicating greater risk) and was related to both subsequent cognitive decline and dementia incidence, according to genetic susceptibility to dementia (reflected by the apolipoprotein E [APOE] ε4 allele and a genetic risk score [GRS]). RESULTS: The LIBRA was associated with higher dementia incidence, with no significant effect modification by genetics (hazard ratio for one point score = 1.09 [95% confidence interval, 1.05; 1.13]) in APOE ε4 non-carriers and = 1.15 [1.08; 1.22] in carriers; P = 0.15 for interaction). Similar findings were obtained with the GRS and with cognitive decline. DISCUSSION: Lifestyle-based prevention may be effective whatever the genetic susceptibility to dementia.

Exploring the Causal Relationship Between Modifiable Exposures and Diabetes Mellitus: A Two-Sample Mendelian Randomization Analysis.

Background Observational studies link lifestyle factors to diabetes, but confounding limits causal inference. This study employed Mendelian randomization (MR) to investigate the potential causal effects of major dietary, obesity, smoking, and physical activity exposures on diabetes risk. Methods A two-sample MR framework integrated FinnGen and United Kingdom Biobank (UKB) data. Genetic instruments for diet (fruits, vegetables, cheese), smoking (initiation, intensity, maternal), body mass index (BMI), and physical activity came from various consortia (n=64, 949-632, 802). Associations with diabetes odds were assessed using inverse-variance weighted analysis. Results Fruit and cheese intake and physical activity per standard deviation increase causally reduced diabetes risk in both cohorts. Conversely, smoking initiation, maternal smoking around birth, and BMI per standard deviation increase causally increased diabetes risk in both cohorts. Coffee increased diabetes risk only in FinnGen, whereas smoking intensity increased diabetes risk only in UKB. Conclusion This study provides robust evidence that modifiable lifestyle factors may have causal effects on diabetes risk. Fruit, cheese, and physical activity may protect against diabetes, whereas smoking, maternal smoking, and higher BMI appear to increase risk. Findings support public health interventions targeting diet, physical activity, smoking cessation, and healthy weight to combat the global diabetes epidemic.

Causal relationships between modifiable risk factors and polycystic ovary syndrome: a comprehensive Mendelian randomization study.

Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study.

BACKGROUND: The intricate etiology of autoimmune liver disease (AILD) involves genetic, environmental, and other factors that yet to be completely elucidated. This study comprehensively assessed the causal association between genetically predicted modifiable risk factors and AILD by employing Mendelian randomization. METHODS: Genetic variants associated with 29 exposure factors were obtained from genome-wide association studies (GWAS). Genetic association data with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also obtained from publicly available GWAS. Univariate and multivariate Mendelian randomization analyses were performed to identify potential risk factors for AILD. RESULTS: Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, 95%CI 1.423-1.843, P = 2.506 × 10- 13) was significantly associated with an increased risk of AIH. Genetically predicted smoking initiation (OR = 1.637, 95%CI 1.055-2.540, P = 0.028), lower coffee intake (OR = 0.359, 95%CI 0.131-0.985, P = 0.047), cholelithiasis (OR = 1.134, 95%CI 1.023-1.257, P = 0.017) and higher C-reactive protein (CRP) (OR = 1.397, 95%CI 1.094-1.784, P = 0.007) were suggestively associated with an increased risk of AIH. Genetically predicted inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127-1.303, P = 2.015 × 10- 7) and RA (OR = 1.417, 95%CI 1.193-1.683, P = 7.193 × 10- 5) were significantly associated with increased risk of PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI 1.005-1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1.086, 95%CI 1.017-1.160, P = 0.014) and higher CRP (OR = 1.199, 95%CI 1.019-1.410, P = 0.028) were suggestively associated with an increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560-0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699-0.995, P = 0.044) levels were suggestive protective factors for PBC. Genetically predicted smoking initiation (OR = 0.630, 95%CI 0.462-0.860, P = 0.004) was suggestively associated with a decreased risk of PSC. Genetically predicted IBD (OR = 1.252, 95%CI 1.164-1.346, P = 1.394 × 10- 9), RA (OR = 1.543, 95%CI 1.279-1.861, P = 5.728 × 10- 6) and lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141-0.510, P = 6.172 × 10- 5) were positively associated with an increased risk of PSC. CONCLUSIONS: Evidence on the causal relationship between 29 genetically predicted modifiable risk factors and the risk of AIH, PBC, and PSC is provided by this study. These findings provide fresh perspectives on the management and prevention strategies for AILD.

Systemic inflammation, lifestyle behaviours and dementia: A 10-year follow-up investigation.

Objectives: Lifestyle behaviours have been linked to dementia incidence, but their cumulative impact on dementia and the underlying mechanisms remain poorly understood. This study investigated the association of co-occurring lifestyle behaviours with dementia incidence and the mediating role of systemic inflammation in this association. Methods: The sample comprised 3131 participants (55.2% female) from the English Longitudinal Study of Ageing aged 52-92 years at baseline (2008/09). Self-reported baseline lifestyle behaviours (alcohol intake, fruit and vegetable consumption, smoking, physical activity, sleep duration, social engagement, and cognitive activity) were summed to derive an index of lifestyle behaviours, ranging from 0 to 7, with higher scores denoting a higher number of health-risk behaviours. Incident dementia cases (n = 130, 4.2%) were identified through doctor-diagnosed dementia, informant interviews, and health records between 2014/15 and 2018/19. Systemic inflammation was measured through fasting plasma concentrations of C-reactive protein in 2012/13. Results: Binary logistic regression models indicated that the odds of subsequent dementia increased by 1.19 for each additional health-risk behaviour (95% confidence intervals: 1.04, 1.37, p = 0.014) after adjusting for age, sex, ethnicity, wealth, education, marital status, body mass index, coronary heart disease, hypertension, stroke, and depression. However, this association was not mediated by C-reactive protein. Conclusions: Co-occurring health-risk behaviours were associated with higher dementia incidence up to 10 years later, underscoring the importance of modifying health-risk behaviours for the prevention of dementia. Systemic inflammation did not explain the association between behaviours and dementia.

Perspectives for the Prevention of Noncommunicable Diseases in Tanzania: Is Knowledge Translated into Practice?

Background: In Tanzania, where over a third of the society is impoverished, the burden of NCDs which account for about two-fifths of all disability-adjusted life years (DALYs) and one-third of premature deaths has doubled in the past two decades. However, notwithstanding a wider realization of the escalating burden of NCDs across Tanzania, the link between NCD awareness and lifestyle practices at the population level is not well characterized. We aimed to establish the gap between NCD knowledge and healthy behaviors. Methods: This multi-regional community-based cross-sectional study was conducted in 5 regions of Tanzania between September 2022 and June 2023. A 22-item standardized tool evaluating various NCD risk behaviors was used in knowledge assessment and a cut-off of ≥70% was used to denote good knowledge. Bivariate analyses were performed to compare knowledge of NCD risk factors across various NCD risk subgroups. All tests were two tailed, and the significance was set at p<0.05. Results: A total of 5121 individuals were consecutively enrolled. The mean age was 47.2 years and females comprised over three-fifths (60.8%) of the participants. With regard to behavioral NCD risks, physical inactivity, unhealthy diet, smoking and alcohol consumption were present in 79.0%, 70.2%, 2.1% and 17.6% of participants, respectively. Moreover, biological risk factors, ie, excess body weight, hypertension, and diabetes were present in 68.4%, 55.8% and 13.0% of participants, respectively. The mean knowledge score was 77.1% and 70.3% of participants demonstrated good knowledge of NCD risk factors. Except for smoking, individuals who showed awareness of various NCD risk factors were found to have significant rates of risky behaviors. Conclusion: Despite sufficient NCD risk knowledge, incongruent lifestyle practices persist, highlighting a crucial concern. This suggests that awareness of NCDs and their risks may influence motivation for change but may not necessarily result in lifestyle modification.

Methodological examination of the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score.

The objective of this study was to examine the impact of methodological changes to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score on associations with risk for all-cause mortality, cancer mortality, and cancer risk jointly among older adults in the NIH-AARP Diet and Health Study. Weights were incorporated for each Score component; a continuous point scale was developed in place of the Score's fully discrete cut-points; and cut-point values were changed for physical activity and red meat based on evidence-based recommendations. Exploratory aims also examined the impact of separating components with more than one sub-component and whether all components were necessary to retain within this population utilizing a penalized scoring approach. Findings suggested weighting the original 2018 WCRF/AICR Score improved the score's predictive performance in association with all-cause mortality and provided more precise estimates in relation to cancer risk and mortality outcomes. The importance of healthy weight, physically activity, and plant-based foods in relation to cancer and overall mortality risk were highlighted in this population of older adults. Further studies are needed to better understand the consistency and generalizability of these findings across other populations.

Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru.

BACKGROUND: Limited evidence exists on the population attributable fraction (PAF) of cancer cases and deaths in Latin America. In Peru several studies have been published regarding the PAF of various risk factors and their associated diseases. The objective of this study was to estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, before the COVID-19 pandemic in the population of 15 years old and older. METHODS: An ecological study was conducted using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, the relative risk associated with each factor, and the number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the PAF and confidence intervals. The number of new cancer cases and deaths attributed to each risk factor was determined by multiplying the number of cases and deaths in each gender by the PAF of each risk factor. FINDINGS: In Peru, 38.5% of new cases (34.5% in men and 42% in women) and 43.4% of cancer-related deaths (43.4% in men and 43.4% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,308 (10,439 in men and 14,869 in women) and the number of deaths attributable to cancer was 14,839 (6,953 in men and 7,886 in women). The predominant modifiable risk factors contributing to the highest number of cases and deaths were HPV infection (4,563 cases, 2,409 deaths), current tobacco use (3,348 cases, 2,180 deaths), and helicobacter pylori infection (2,677 cases, 1,873 deaths). Among the risk factors, oncogenic infections constituted the group with the highest PAF (16.6% for cases, 19.2% for deaths) followed by other unhealthy lifestyle factors (14.2% for cases, 16.7% for deaths), tobacco (7.2% for cases, 7.2% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths). CONCLUSIONS: Prior to the COVID-19 pandemic, 38.5% of cancer cases and 43.4% of cancer-related deaths in Peru were linked to modifiable risk factors in the population of 15 years old and older. Most preventable cancer cases and deaths were related to oncogenic infections, primarily caused by HPV and helicobacter pylori, followed by tobacco and obesity.