Alterations in gut microbiota and bile acids by proton-pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance.

Several observational studies have suggested that proton-pump inhibitor (PPI) use might increase diabetes risk, but the mechanism remains unclear. This study aimed to investigate the effects of PPI use on gut microbiota and bile acids (BAs) profiles, and to explore whether these changes could mediate the association of PPIs use with fasting blood glucose (FBG) levels and insulin resistance (IR) in Chinese population. A cross-sectional study was conducted in Shenzhen, China, from April to August 2021, enrolled 200 eligible patients from the local hospital. Participants completed a questionnaire and provided blood and stool samples. Gut microbiome was measured by16S rRNA gene sequencing, and bile acids were quantified by UPLC-MS/MS. Insulin resistance (IR) was assessed using the Homeostasis Model Assessment 2 (HOMA2-IR). PPI use was positively associated with higher levels of FBG and HOMA2-IR after controlling for possible confounders. PPI users exhibited a decreased Firmicutes and an increase in Bacteroidetes phylum, alongside higher levels of glycoursodeoxycholic acid (GUDCA) and taurochenodeoxycholic acid (TCDCA). Higher abundances of Bacteroidetes and Fusobacterium as well as higher levels of TCDCA in PPI users were positively associated with elevated FBG or HOMA2-IR. Mediation analyses indicated that the elevated levels of FBG and HOMA2-IR with PPI use were partially mediated by the alterations in gut microbiota and specific BAs (i.e., Fusobacterium genera and TCDCA). Long-term PPI use may increase FBG and HOMA2-IR levels, and alterations in gut microbiota and BAs profiles may partially explain this association.

Regular use of paracetamol and risk of liver cancer: a prospective cohort study.

BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer. METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up. RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up. CONCLUSION: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

Lipidomic markers for the prediction of progression from mild cognitive impairment to Alzheimer's disease.

Dementia is a well-known syndrome and Alzheimer's disease (AD) is the main cause of dementia. Lipids play a key role in the pathogenesis of AD, however, the prediction value of serum lipidomics on AD remains unclear. This study aims to construct a lipid score system to predict the risk of progression from mild cognitive impairment (MCI) to AD. First, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model to select the lipids that can signify the progression from MCI to AD based on 310 older adults with MCI. Then we constructed a lipid score based on 14 single lipids using Cox regression and estimated the association between the lipid score and progression from MCI to AD. The prevalence of AD in the low-, intermediate- and high-score groups was 42.3%, 59.8%, and 79.8%, respectively. The participants in the intermediate- and high-score group had a 1.65-fold (95% CI 1.10 to 2.47) and 3.55-fold (95% CI 2.40 to 5.26) higher risk of AD, respectively, as compared to those with low lipid scores. The lipid score showed moderate prediction efficacy (c-statistics > 0.72). These results suggested that the score system based on serum lipidomics is useful for the prediction of progression from MCI to AD.

Genetic risk, adherence to healthy lifestyle behaviors, and risk of cholelithiasis: A population-based cohort study.

OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.

Associations of maternal and personal smoking with all-cause and cause-specific mortality risk and life expectancy: a prospective cohort study.

OBJECTIVES: The aim of this study was to evaluate the individual and combined effects of maternal smoking during pregnancy (MSDP) and personal smoking on mortality and life expectancy. STUDY DESIGN: A prospective cohort study based on the UK Biobank, with a median follow-up of 12.47 years. METHODS: This study employed multivariate Cox regression to determine the relative risks of mortality from all causes and specific diseases according to maternal and/or personal smoking status and pack-years of smoking (0, 1-20, 21-30, >30). Additionally, this study estimated the additive interaction between the two exposures. Life table analyses were performed using the estimated age-specific mortality rates to forecast life expectancy. RESULTS: Results indicated that MSDP elevated the risk of all-cause mortality (HR = 1.12, 95% CI: 1.09-1.15) and mortality due to neoplasms (HR = 1.10, 95% CI: 1.06-1.12), circulatory (HR = 1.13, 95% CI: 1.06-1.19), respiratory (HR = 1.27, 95% CI: 1.16-1.40) and digestive system diseases (HR = 1.22, 95% CI: 1.08-1.38). Notably, both multiplicative and additive interactions were observed between maternal and personal smoking, with Relative Excess Risk due to Interaction (RERI) values for mortality from all causes, neoplasms, circulatory, and respiratory diseases being 0.21, 0.22, 0.16, and 0.76, respectively. This study also found a trend towards shorter gained life expectancy when maternal smoking and increasing pack-years of personal smoking were combined. CONCLUSIONS: In this cohort study of UK Biobank, MSDP was associated with an increased risk of all-cause mortality and reduced life expectancy, suggesting that quitting smoking during pregnancy might have health and longevity benefits for both generations.

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts.

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.

Genetic factors, adherence to healthy lifestyle behaviors, and risk of bladder cancer.

BACKGROUND: Genetic and lifestyle factors both contribute to the pathogenesis of bladder cancer, but the extent to which the increased genetic risk can be mitigated by adhering to a healthy lifestyle remains unclear. We aimed to investigate the association of combined lifestyle factors with bladder cancer risk within genetic risk groups. METHODS: We conducted a prospective study of 375 998 unrelated participants of European ancestry with genotype and lifestyle data and free of cancer from the UK biobank. We generated a polygenic risk score (PRS) using 16 single nucleotide polymorphisms and a healthy lifestyle score based on body weight, smoking status, physical activity, and diet. Cox models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of genetic and lifestyle factors on bladder cancer. RESULTS: During a median follow-up of 11.8 years, 880 participants developed bladder cancer. Compared with those with low PRS, participants with intermediate and high PRS had a higher risk of bladder cancer (HR 1.29, 95% CI 1.07-1.56; HR 1.63, 95% CI 1.32-2.02, respectively). An optimal lifestyle was associated with an approximately 50% lower risk of bladder cancer than a poor lifestyle across all genetic strata. Participants with a high genetic risk and a poor lifestyle had 3.6-fold elevated risk of bladder cancer compared with those with a low genetic risk and an optimal lifestyle (HR 3.63, 95% CI 2.23 -5.91). CONCLUSIONS: Adhering to a healthy lifestyle could substantially reduce the bladder cancer risk across all genetic strata, even for high-genetic risk individuals. For all populations, adopting an intermediate lifestyle is more beneficial than a poor one, and adhering to an optimal lifestyle is the ideal effective strategy for bladder cancer prevention.

Adherence to Antiretroviral Therapy and Its Predictive Factors Among People Living with HIV in China: A Behavioral Theory-Based Prospective Cohort Study.

BACKGROUND: Free antiretroviral therapy (ART) has been expanded to all people living with HIV (PLWH) in China since 2016, and adherence to ART has been shown to be the primary determinant of viral suppression. This study aimed to investigate the ART adherence and its associated factors among PLWH in China in the context of a scaling-up of treatment policy. METHOD: A prospective cohort study was conducted from June 2016 to May 2018 in Guangzhou, China. A total of 400 eligible participants were recruited from the Guangzhou Eighth People's hospital in Guangzhou, China. The Theory of Planned Behavior and the Behavioral Maintenance Theory were applied to guide the questionnaire design. Participants were invited to completed self-administered questionnaire at baseline and months 3 and 6 post-baseline. Logistic regression models were fitted to explore factors associated with ART adherence. RESULTS: Of the 400 participants, the prevalence of optimal ART adherence was 83.6% at month 3 and 83.3% at month 6. The baseline attitude (ORa = 1.11, P < 0.05), behavioral intention (ORa = 1.90, P < 0.05), and outcome expectations (ORa = 1.09, P < 0.001) predicted ART adherence at month 3 in adjusted analyses, but only outcome expectations (ORa = 1.09, P < 0.01) remained significant in the final multivariate model. At month 3, negative experiences (ORa = 0.62, P < 0.05) were the only predictor of adherence at month 6. CONCLUSION: Approximately 15% of participants reported suboptimal ART adherence. The developments of tailored interventions that target factors such as outcome expectations at baseline and negative experiences during treatment are warranted.

High serum uric acid may associate with the increased risk of colorectal cancer in females: A prospective cohort study.

Elevated serum uric acid (SUA) levels have been previously reported to play a role in multiple types of cancers. However, epidemiological studies evaluating SUA levels and colorectal cancer risk remain sparse. This cohort study included 444 462 participants between the ages of 40 and 69 years from the UK Biobank, followed up from 2006 to 2010. Multivariable adjusted Cox regression models were used to estimate hazard ratios (HRs). During a mean follow-up of 6.6 years, 2033 and 855 cases of colon and rectal cancers, respectively, were diagnosed. The multivariable-adjusted HRs for risks of colon cancer in the lowest uric acid categories (≤3.5 mg/dL) compared with the reference groups were 1.31 (95% confidence interval [CI] = 0.75-2.29) in males and 1.26 (95% CI = 1.03-1.55) in females. The HRs in the highest uric acid groups (>8.4 mg/dL) were 1.16 (95% CI = 0.83-1.63) in males and 2.00 (95% CI = 1.02-3.92) in females. The corresponding HRs of rectal cancer in the lowest uric acid groups compared with the reference group were 2.21 (95% CI = 1.15-4.23) in males and 0.98 (95% CI = 0.66-1.45) in females. The HRs in the highest uric acid groups were 1.35 (95% CI = 0.82-2.23) in males and 3.81 (95% CI = 1.38-10.56) in females. In conclusion, SUA showed a U-shaped association with colon cancer risk in both male and female populations. The same pattern was observed in male patients with rectal cancer. However, SUA levels were positively associated with occurrence of rectal cancer in female subjects.

Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis). METHODS: This was a pooled analysis of the Nurses' Health Study (NHS, n = 82,869), NHS II (n = 95,141), and UK Biobank (n = 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications. RESULTS: We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22-1.65; number needed to harm, 3770; 95% CI, 3668-4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16-1.65). CONCLUSIONS: Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.

Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies.

OBJECTIVE: The association between the regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomised controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes. METHOD: This is a prospective analysis of 204 689 participants free of diabetes in the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications. RESULTS: We documented 10 105 incident cases of diabetes over 2 127 471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users (HR 1.24, 95% CI 1.17 to 1.31). The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 (95% CI 0.93 to 1.19) for participants who used PPIs for >0-2 years and 1.26 (95% CI 1.18 to 1.35) for participants who used PPIs for >2 years compared with non-users. CONCLUSIONS: Regular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.

Association of body composition with risk of overall and site-specific cancers: A population-based prospective cohort study.

Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454 079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27 794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk.

No Associations Between Regular Use of Proton Pump Inhibitors and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort of 0.44 Million Participants.

INTRODUCTION: The association between proton pump inhibitors' (PPIs) use and mortality remains unclear. METHODS: This was a prospective analysis of 440,840 UK residents and 13,154 deaths. We evaluated the associations with multivariate Cox regression. RESULTS: After adjusting for confounders, such as over health status and longstanding diseases, the regular use of PPIs was not associated with an increased risk of all-cause mortality and mortality due to neoplasms, circulatory system diseases, respiratory system diseases, digestive system diseases, external causes, and other causes. DISCUSSION: Regular use of PPIs was not associated with an increased risk of all-cause and cause-specific mortality.

Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials.

BACKGROUND: Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. METHODS: This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). RESULTS: We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. CONCLUSIONS: Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.

Metabolic syndrome and its component traits present gender-specific association with liver cancer risk: a prospective cohort study.

BACKGROUND & AIMS: Little is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort. METHODS: We included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method. RESULTS: Over a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27-1.72] and central obesity [HR 1.65, 95% CI 1.18-2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk. CONCLUSIONS: MetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.

Associations between antiretroviral therapy-related experiences and mental health status among people living with HIV in China: a prospective observational cohort study.

BACKGROUND: Mental health problems (e.g., depression and anxiety) are among the most commonly reported comorbidities of HIV. Antiretroviral therapy (ART) coverage has increased sharply. The purposes of this prospective cohort study were to investigate the ART-related experiences and whether they were associated with mental health problems among a sample of people living with HIV undergoing ART in China. METHODS: The participants were 400 people living with HIV who had started ART for the first time in Guangzhou city. They were followed-up 1-year after ART initiation. Probable depression and moderate/severe anxiety were measured at baseline and Month 12, while experiences related to ART (e.g., side effects and regained self-confidence) were measured at Month 6. Univariate and multivariate logistic regressions were used to explore the associations between baseline characteristics, ART-related experiences and mental health status. RESULTS: Among the 300 participants (75.0%) who completed all three surveys, a significant decline in prevalence of probable depression (23.0% at baseline vs. 14.0% at Month 12, P = 0.002) and moderate/severe anxiety (14.7% at baseline vs. 8.7% at Month 12, P = 0.023) was observed during the follow-up period. After adjustment for mental health status and potential confounders at baseline, a number of ART-related experiences at Month 6 were associated with probable depression and/or moderate/severe anxiety measured at Month 12. Improved physical health, relationships with sexual partners, and self-confidence were associated with decreased mental health issues, while the side effects of ART, AIDS-related symptoms, and inconvenience in daily life due to ART use were associated with increased mental health issues. CONCLUSIONS: ART-related experiences were associated with mental health problems, tailored mental health promotion interventions targeting these experiences are needed.

Metabolic syndrome and risk of pancreatic cancer: A population-based prospective cohort study.

Metabolic syndrome (MetS) and its components may link to pancreatic cancer risk; however, current epidemiological evidence is limited, and the potential mechanisms underlying the associations remain unclear. To investigate this, we carried out this prospective cohort study of 474 929 participants without a diagnosis of cancer based on UK Biobank dataset. MetS was defined according to the International Diabetes Federation criteria and pancreatic cancer was identified through linkage to UK cancer registries (median follow-up time: 6.6 years). We evaluated hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demography and lifestyle factors. Restricted cubic spline was performed for each MetS component to investigate their possible nonlinear associations with risk of pancreatic cancer. During 3 112 566 person-years of follow-up, 565 cases of pancreatic cancer were identified. Individuals with MetS (HR = 1.31, 95% CI, 1.09-1.56), central obesity (HR = 1.24, 95% CI, 1.02-1.50) and hyperglycemia (HR = 1.60, 95% CI, 1.31-1.97) had increased risk of pancreatic cancer. Higher waist circumference (WC) and blood glucose were independently associated with pancreatic cancer, with no evidence against nonlinearity. Although elevated CRP (≥1.00 mg/dL) showed a positive association with the risk for pancreatic cancer, the effect was substantially increased only in participants with MetS and CRP ≥1.00 mg/dL. Our study demonstrated a positive association between MetS and increased risk of pancreatic cancer, with two of the MetS components, WC and blood glucose, showing independent associations in linear manner. Our study also suggested a potential joint effect of MetS and CRP in pancreas tumorigenesis.

Intention to start ART after the launch of expanded treatment strategy among people living with HIV in China: a behavioral theory-based cross-sectional study.

This study investigated the prevalence of intention to start antiretroviral therapy (ART) immediately among people living with HIV (PLWH) in China and associated perceptions toward ART based on behavioral theories. The study was initiated after the launch of an expanded ART strategy. A cross-sectional study was conducted among 450 PLWH who were ART naive in the city of Guangzhou, China, from June 2016 to February 2017. Among the participants, 311 (69.1%) showed intention to start ART immediately. The summary logistic regression analysis indicated that intention to start ART immediately was significantly associated with perceived severity [multivariate odds ratios (ORm) = 1.62, 95%CI = 1.15-2.28, p < 0.01], perceived barriers (ORm =0.56, 95%CI = 0.38-0.84, p < 0.01), self-efficacy (ORm =2.90, 95%CI = 2.05-4.09, p < 0.001), and subjective norms (ORm =1.95, 95%CI = 1.17-3.25, p < 0.05). The intention to start ART immediately among PLWH in Guangzhou was below the 90-90-90 target. Further promotion research should focus on these perceptional factors.

Assessment of the health status and health service perceptions of international migrants coming to Guangzhou, China, from high-, middle- and low-income countries.

BACKGROUND: China, which used to be an export country for migrants, has become a new destination for international migrants due to its rapid economic growth. However, little empirical data is available on the health status of and health service access barriers faced by these international migrants. METHODS: Foreigners who visited the Guangzhou Municipal Exit-Entry Administration Office to extend their visas were invited to participate in the study. Quantitative data were collected using electronic questionnaire in 13 languages. The participants were characterised by the income level of their country of origin (high-, middle- and low-income countries (HICs, MICs and LICs, respectively)), and the key factors associated with their health status, medical insurance coverage and perceptions of health services in China were examined. RESULTS: Overall, 1146 participants from 119 countries participated in the study, 57.1, 25.1 and 17.8% of whom were from MICs, HICs and LICs, respectively. Over one fifth of the participants experienced health problems while staying in China, and about half had no health insurance. Although the participants from HICs were more likely than those from MICs and LICs to have medical insurance, they were also more likely to have health problems. Furthermore, 43.0, 45.0 and 12.0% of the participants thought that the health services in China were good, fair and poor, respectively. Among the participants, those from HICs were less likely to have positive feedback. CONCLUSIONS: Our study is the first to report a quantitative survey of the health status, health insurance coverage, and health service perceptions of a diverse and surging population of international migrants in China. The findings call for more in-depth studies on the challenges presented by the increasing global migration to the health system.

Intention to initiate antiretroviral therapy (ART) among people living with HIV in China under the scaling-up of ART: the role of healthcare workers' recommendations.

BACKGROUND: The early initiation of antiretroviral therapy (ART) for people living with HIV (PLWH) benefits both individuals and societies. However, little is known about the intention to initiate ART among PLWH in China in the context of a scaling-up of treatment or how the recommendations of healthcare workers affect this intention. METHODS: A total of 451 ART-naïve PLWH were recruited from communities in Guangzhou, China for this study. Data were collected by trained physicians via face-to-face interviews. Logistic regression models were fitted for the data analyses. RESULTS: Of the participants, 93.8% were male, 72.7% were infected via homosexual behaviour and 68.5% reported an intention to initiate ART. In the latter category, 77.8, 41.9 and 20.0% of respondents received strong recommendations to initiate ART from healthcare workers at the Centres for Disease Control and Prevention (CDC), community healthcare centres and non-governmental organisations (NGOs), respectively. After adjusting for potential confounders, depression, anxiety and strong recommendations from healthcare workers at the CDC and NGOs correlated significantly with ART intention. In the adjusted final hierarchical logistic regression model, the duration of infection [multivariate odds ratio (ORm) = 0.30, p < 0.001], route of HIV infection (ORm = 0.18, p < 0.01), infection status of the current spouse/regular sex partner (ORm = 0.21-0.23, p < 0.01), anxiety (ORm = 2.44-2.65, p < 0.05) and strong recommendations from CDC physicians (ORm = 3.67, p < 0.01) or NGOs workers (ORm = 3.67, p < 0.01) were independently associated with the ART intention, whereas a recommendation from a community healthcare centre physician was not. CONCLUSIONS: In Guangzhou, the prevalence of ART intention was below the 90-90-90 targets. Further studies aimed at an in-depth understanding and encouragement of health care workers' perceptions regarding early ART are warranted as a means of scaling up new ART strategies.