Overall and subgroup prevalence of non-alcoholic fatty liver disease and prevalence of advanced fibrosis in the United States: An updated national estimate in National Health and Nutrition Examination Survey (NHANES) 2011-2018.

INTRODUCTION AND OBJECTIVES: Data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in subgroups of the United States (US) population are limited. This study was conducted to estimate NAFLD prevalence overall and by subgroups, and prevalence of NAFLD with advanced fibrosis. MATERIALS AND METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data, a cross-sectional study was conducted. NAFLD was defined as having a US Fatty Liver Index (USFLI) ≥ 30 in the absence of other causes of liver disease, including excessive alcohol intake, chronic hepatitis B, and chronic hepatitis C. Likelihood for having advanced fibrosis was determined by the calculated NAFLD fibrosis score (NFS; high ≥ 0.676; low < -1.445) and fibrosis-4 index (FIB-4; high ≥ 2.67; low < 1.30). RESULTS: The weighted national prevalence of NAFLD in US adults was 26.7% (95% confidence interval: 25.3%-28.1%). Prevalence was higher among those aged ≥ 65 years, males, Mexican Americans, with BMI ≥ 35 kg/m2 (class 2 and 3 obesity) and with type 2 diabetes (T2D). Of those meeting the USFLI criterion for NAFLD, 18.1% and 3.7% were determined as having a high probability of advanced fibrosis based on NFS ≥ 0.676 and FIB-4 ≥ 2.67 cut-off values, respectively. CONCLUSIONS: This study supports an increased prevalence of NAFLD in specific subpopulations (aged ≥ 65 years, males, Mexican Americans, obese population, and patients with T2D). The observed difference in the prevalence of advanced fibrosis as estimated by NFS and FIB-4 highlights the challenge of choosing optimal cut-off values.

Wildland Fires Worsened Population Exposure to PM2.5 Pollution in the Contiguous United States.

As wildland fires become more frequent and intense, fire smoke has significantly worsened the ambient air quality, posing greater health risks. To better understand the impact of wildfire smoke on air quality, we developed a modeling system to estimate daily PM2.5 concentrations attributed to both fire smoke and nonsmoke sources across the contiguous U.S. We found that wildfire smoke has the most significant impact on air quality in the West Coast, followed by the Southeastern U.S. Between 2007 and 2018, fire smoke contributed over 25% of daily PM2.5 concentrations at ∼40% of all regulatory air monitors in the EPA's air quality system (AQS) for more than one month per year. People residing outside the vicinity of an EPA AQS monitor (defined by a 5 km radius) were subject to 36% more smoke impact days compared with those residing nearby. Lowering the national ambient air quality standard (NAAQS) for annual mean PM2.5 concentrations to between 9 and 10 µg/m3 would result in approximately 35-49% of the AQS monitors falling in nonattainment areas, taking into account the impact of fire smoke. If fire smoke contribution is excluded, this percentage would be reduced by 6 and 9%, demonstrating the significant negative impact of wildland fires on air quality.

Wildfire worsens population exposure to PM2.5 pollution in the Continental United States.

As wildfires become more frequent and intense, fire smoke has significantly worsened ambient air quality, posing greater health risks. To better understand the impact of wildfire smoke on air quality, we developed a modeling system to estimate daily PM2.5 concentrations attributed to both fire smoke and non-smoke sources across the Continental U.S. We found that wildfire smoke has the most significant impact on air quality in the West Coast, followed by the Southeastern U.S. Between 2007 and 2018, fire smoke affected daily PM2.5 concentrations at 40% of all regulatory air monitors in EPA's Air Quality System (AQS) for more than one month each year. People residing outside the vicinity of an EPA AQS monitor were subject to 36% more smoke impact days compared to those residing nearby. Lowering the national ambient air quality standard (NAAQS) for annual mean PM2.5 concentrations to between 9 and 10 µg/m3 would result in approximately 29% to 40% of the AQS monitors falling in nonattainment areas without taking into account the contribution from fire smoke. When fire smoke impact is considered, this percentage would rise to 35% to 49%, demonstrating the significant negative impact of wildfires on air quality.

Association of Wildfire Exposure While Recovering From Lung Cancer Surgery With Overall Survival.

Importance: With a changing climate, wildfire activity in the US has increased dramatically, presenting multifaceted and compounding health hazards. Individuals discharged from the hospital following surgical resection of non-small cell lung cancer (NSCLC) are potentially at higher risk from wildfires' health hazards. Objective: To assess the association between wildfire exposure and postoperative long-term overall survival among patients with lung cancer in the US. Design, Setting, and Participants: In this cohort study, individuals who underwent curative-intent NSCLC resection between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. Daily wildfire information was aggregated at the zip code level from the National Aeronautics and Space Administration Fire Information for Resource Management System. The data analysis was performed between July 19, 2022, and April 14, 2023. Exposure: An active wildfire detected at the zip code of residence between 0 and 3, 4 and 6, or 7 and 12 months after NSCLC surgery. Main Outcome: Overall survival was defined as the interval between age at hospital discharge and age at death, last contact, or study end, whichever came first. Cox proportional hazards were used for estimating hazard ratios (HRs) adjusted for sex, region, metropolitan category, health insurance type, comorbidities, tumor size, lymph node involvement, era, and facility type. Results: A total of 466 912 individuals included in the study (249 303 female and [53.4] and 217 609 male [46.6%]; mean [SD] age at diagnosis, 67.3 [9.9] years), with 48 582 (10.4%) first exposed to a wildfire between 0 and 3 months, 48 328 (10.6%) between 4 and 6 months, and 71 735 (15.3%) between 7 and 12 months following NSCLC surgery. Individuals exposed to a wildfire within 3 months (adjusted HR [AHR], 1.43; 95% CI, 1.41-1.45), between 4 and 6 months (AHR, 1.39; 95% CI, 1.37-1.41), and between 7 and 12 months (AHR, 1.17; 95% CI, 1.15-1.19) after discharge from the hospital following stage I to III NSCLC resection had worse overall survival than unexposed individuals. Conclusions: In this cohort study, wildfire exposure was associated with worse overall survival following NSCLC surgical resection, suggesting that patients with lung cancer are at greater risk from the health hazards of wildfires and need to be prioritized in climate adaptation efforts.

Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data.

Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children's longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010-2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed (N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days (smoke-day) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1-12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13-24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.

Associations of Air Pollution and Serum Biomarker Abnormalities in Individuals with Hemodialysis-Dependent Kidney Failure.

BACKGROUND: Ambient particles with a median aerodynamic diameter of <2.5 µm (PM2.5) is a ubiquitous air pollutant with established adverse health consequences. While postulated to promote a systemic inflammatory response, limited studies have demonstrated changes in serum biomarkers related to PM2.5 exposure. We aim to examine associations between short-term PM2.5 exposure and commonly measured biomarkers known to be affected by inflammation among patients receiving maintenance in-center hemodialysis. METHODS: We conducted a retrospective open cohort study from January 1, 2008, to December 31, 2014. Adult hemodialysis patients were identified from the United States Renal Data System and linked at the patient level to laboratory data from a large dialysis organization. Daily ambient PM2.5 was estimated on a 1-km grid and assigned to cohort patients based on the ZIP codes of dialysis clinics. Serum albumin, serum ferritin, transferrin saturation (TSAT), and serum hemoglobin were ascertained from the dialysis provider organization database. Mixed-effect models were used to assess the changes in biomarker levels associated with PM2.5 exposure. RESULTS: The final cohort included 173,697 hemodialysis patients. Overall, the daily ZIP-level ambient PM2.5 averages were 8.4-8.5 µg/m3. A 10-µg/m3 increase in same-day ambient PM2.5 exposure was associated with higher relative risks of lower albumin (relative risk [RR], 1.01; 95% confidence interval [95% CI], 1.01 to 1.02) and lower hemoglobin (RR, 1.02; 95% CI, 1.01 to 1.03). Associations of same-day ambient PM2.5 exposure and higher ferritin and lower TSAT did not reach statistical significance. CONCLUSIONS: Short-term PM2.5 exposure was associated with lower serum hemoglobin and albumin among patients receiving in-center hemodialysis. These findings lend support to the role of inflammation in PM2.5 exposure-outcome associations.

Association Between Long-term Ambient PM2.5 Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients.

RATIONALE & OBJECTIVE: Ambient PM2.5 (particulate matter with a diameter of 2.5 microns) is a ubiquitous air pollutant with established adverse cardiovascular (CV) effects. However, quantitative estimates of the association between PM2.5 exposure and CV outcomes in the setting of kidney disease are limited. This study assessed the association of long-term PM2.5 exposure with CV events and cardiovascular disease (CVD)-specific mortality among patients receiving maintenance in-center hemodialysis (HD). STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 314,079 adult kidney failure patients initiating HD between 2011 and 2016 identified from the US Renal Data System. EXPOSURE: Estimated daily ZIP code-level PM2.5 concentrations were used to calculate each participant's annual average PM2.5 exposure based on the dialysis clinics visited during the 365 days before the outcome. OUTCOME: CV event and CVD-specific mortality were ascertained based on ICD-9/ICD-10 diagnostic codes and recorded cause of death from Centers for Medicare & Medicaid Services form 2746. ANALYTICAL APPROACH: Discrete time hazards models were used to estimate hazards ratios per 1 µg/m3 greater annual average PM2.5, adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and baseline comorbidities. RESULTS: Each 1 µg/m3 greater annual average PM2.5 was associated with a greater rate of CV events (HR, 1.02 [95% CI, 1.01-1.02]) and CVD-specific mortality (HR, 1.02 [95% CI, 1.02-1.03]). The association was more pronounced for people who initiated dialysis at an older age, had chronic obstructive pulmonary disease (COPD) at baseline, or were Asian. Evidence of effect modification was also observed across strata of race, and other baseline comorbidities. LIMITATIONS: Potential exposure misclassification and unmeasured confounding. CONCLUSIONS: Long-term ambient PM2.5 exposure was associated with CVD outcomes among patients receiving maintenance in-center HD. Stronger associations between long-term PM2.5 exposure and adverse effects were observed among patients who were of advanced age, had COPD, or were Asian. PLAIN-LANGUAGE SUMMARY: Long-term exposure to air pollution, also called PM2.5, has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM2.5 and outcomes among patients receiving dialysis, who are individuals with high cardiovascular disease burdens. We conducted an epidemiological study to assess the association between the annual PM2.5 exposure and cardiovascular events and death among patients receiving regular outpatient hemodialysis in the United States between 2011 and 2016. We found a higher risk of heart attacks, strokes, and related events in patients exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older at the start of dialysis, had chronic obstructive pulmonary disease, or were Asian. These findings bolster the evidence base linking air pollution and adverse health outcomes and may inform policy makers and clinicians.

Effects of short-term ambient PM2.5 exposure on cardiovascular disease incidence and mortality among U.S. hemodialysis patients: a retrospective cohort study.

BACKGROUND: Ambient PM2.5 is a ubiquitous air pollutant with demonstrated adverse health impacts in population. Hemodialysis patients are a highly vulnerable population and may be particularly susceptible to the effects of PM2.5 exposure. This study examines associations between short-term PM2.5 exposure and cardiovascular disease (CVD) and mortality among patients receiving maintenance in-center hemodialysis. METHODS: Using the United State Renal Data System (USRDS) registry, we enumerated a cohort of all US adult kidney failure patients who initiated in-center hemodialysis between 1/1/2011 and 12/31/2016. Daily ambient PM2.5 exposure estimates were assigned to cohort members based on the ZIP code of the dialysis clinic. CVD incidence and mortality were ascertained through 2016 based on USRDS records. Discrete time hazards regression was used to estimate the association between lagged PM2.5 exposure and CVD incidence, CVD-specific mortality, and all-cause mortality 1 t adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and comorbidities. RESULTS: Among 314,079 hemodialysis patients, a 10 µg/m3 increase in the average lag 0-1 daily PM2.5 exposure was associated with CVD incidence (HR: 1.03 (95% CI: 1.02, 1.04)), CVD mortality (1.05 (95% CI: 1.03, 1.08)), and all-cause mortality (1.04 (95% CI: 1.03, 1.06)). The association was larger for people who initiated dialysis at an older age, while minimal evidence of effect modification was observed across levels of sex, race, or baseline comorbidities. CONCLUSIONS: Short-term ambient PM2.5 exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM2.5-associated CVD events than younger hemodialysis patients.

Ovarian cancer risk in relation to blood lipid levels and hyperlipidemia: a systematic review and meta-analysis of observational epidemiologic studies.

Epidemiologic evidence regarding association of ovarian cancer risk with blood lipid level and hyperlipidemia is inconsistent. We aimed to synthesize available epidemiologic studies to disentangle associations of cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and hyperlipidemia with ovarian cancer risk. We searched PubMed, EMBASE, and Web of Science for eligible studies. A random-effects model was applied for synthesis. Heterogeneity was evaluated by a Chi-squared test for the Cochran Q statistic and the I-squared value. Subgroup analysis was conducted by design, study locale, and ovarian cancer case number. Sensitivity analysis was conducted for studies adjusting for certain covariates or with superior quality. To explore the potential dose-response relationship, we further synthesized effect measures of moderate levels of cholesterol, triglycerides, HDL-C, and LDL-C. Twelve studies (five cohort and seven case-control studies) were included. In primary meta-analysis, the synthesized risk ratio (RRpool) and 95% confidence interval (CI) suggested that high cholesterol was associated with an increased ovarian cancer risk (RRpool 1.22, 95% CI 1.01-1.48, Cochran P value: 0.40, I2: 0.5%). High HDL-C was associated with a lower ovarian cancer risk (RRpool 0.61, 95% CI 0.40-0.94, Cochran P value: 0.06, I2: 63.7%). We obtained nonsignificant associations for other exposures. Subgroup and sensitivity analyses yielded consistent results as the primary analysis. Only cholesterol showed marginally significant association in synthesis using moderate exposure levels (RRpool 1.18, 95% CI 0.99-1.42, Cochran P value: 0.51, I2: 0.0%). Our study suggests that high blood cholesterol is associated with an increased ovarian cancer risk, whereas the etiological significance of other exposures deserves more investigations.

Association of short-term exposure to ambient PM2.5 with hospital admissions and 30-day readmissions in end-stage renal disease patients: population-based retrospective cohort study.

OBJECTIVES: To examine the effect of short-term exposure to ambient fine particulate matter (PM2.5) on all-cause, cardiovascular and respiratory-related hospital admissions and readmissions among patients receiving outpatient haemodialysis. DESIGN: Retrospective cohort study. SETTING: Inpatient hospitalisation claims identified from the US Renal Data System in 530 US counties. PARTICIPANTS: All patients receiving in-centre haemodialysis between 2008 and 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk of all-cause, cardiovascular and respiratory-related hospital admissions and 30-day all-cause and cause-specific readmission following an all-cause, cardiovascular, and respiratory-related discharges. Readmission risk was evaluated for early (1-7 days postdischarge) and late (8-30 days postdischarge) readmission time periods. Relative risk is expressed per 10 µg/m3 of PM2.5. RESULTS: Same-day ambient PM2.5 was associated with increased hospital admission risk for cardiovascular causes (0.9%, 95% CI 0.2 to 1.7). Greater PM2.5-related associations were observed with 30-day readmission risk. Early-readmission risk was increased by 1.6%-1.8% following all-cause (1.6%, 95% CI 0.6% to 2.6%), cardiovascular (1.8%, 95% CI 0.4% to 3.2%) and respiratory (1.8%, 95% CI 0.4% to 3.2%) discharges; while late-readmission risk increased by 1.2%-1.3% following all-cause and cardiovascular discharges. PM2.5-related associations with readmission risk were greatest for certain cause-specific readmissions ranging 4.0%-6.5% for dysrhythmia and conduction disorder, heart failure, chronic obstructive pulmonary disease, other non-cardiac chest pain or respiratory syndrome and pneumonia. Following all-cause discharges, the cause-specific early-readmission risk was increased by 6.5% (95% CI 3.5% to 9.6%) for pneumonia, 4.8% (95% CI 2.3% to 7.4%) for dysrhythmia and conduction disorder, 3.7% (95% CI 1.4% to 6.0%) for heart failure and 2.7% (95% CI 1.2% to 4.2%) for other non-cardiac chest pain or respiratory syndrome-related causes. CONCLUSIONS: Daily ambient PM2.5 was associated with an increased risk of cardiovascular admissions and 30-day readmissions following cardiopulmonary-related discharges in a vulnerable end-stage renal disease population. In the first week following discharge, greater PM2.5-related risk of rehospitalisation was identified for some diagnoses.

Mortality in US Hemodialysis Patients Following Exposure to Wildfire Smoke.

BACKGROUND: Wildfires are increasingly a significant source of fine particulate matter (PM2.5), which has been linked to adverse health effects and increased mortality. ESKD patients are potentially susceptible to this environmental stressor. METHODS: We conducted a retrospective time-series analysis of the association between daily exposure to wildfire PM2.5 and mortality in 253 counties near a major wildfire between 2008 and 2012. Using quasi-Poisson regression models, we estimated rate ratios (RRs) for all-cause mortality on the day of exposure and up to 30 days following exposure, adjusted for background PM2.5, day of week, seasonality, and heat. We stratified the analysis by causes of death (cardiac, vascular, infectious, or other) and place of death (clinical or nonclinical setting) for differential PM2.5 exposure and outcome classification. RESULTS: We found 48,454 deaths matched to the 253 counties. A 10-µg/m3 increase in wildfire PM2.5 associated with a 4% increase in all-cause mortality on the same day (RR, 1.04; 95% confidence interval [95% CI], 1.01 to 1.07) and 7% increase cumulatively over 30 days following exposure (RR, 1.07; 95% CI, 1.01 to 1.12). Risk was elevated following exposure for deaths occurring in nonclinical settings (RR, 1.07; 95% CI, 1.02 to 1.12), suggesting modification of exposure by place of death. "Other" deaths (those not attributed to cardiac, vascular, or infectious causes) accounted for the largest portion of deaths and had a strong same-day effect (RR, 1.08; 95% CI, 1.03 to 1.12) and cumulative effect over the 30-day period. On days with a wildfire PM2.5 contribution >10 µg/m3, exposure accounted for 8.4% of mortality. CONCLUSIONS: Wildfire smoke exposure was positively associated with all-cause mortality among patients receiving in-center hemodialysis.

Chronic kidney disease among US adults with type 2 diabetes and cardiovascular diseases: A national estimate of prevalence by KDIGO 2012 classification.

AIM: Data on prevalence of chronic kidney disease (CKD) among US adults with type 2 diabetes (T2D) and cardiovascular diseases (CVD) are limited. The aim of this study was to provide such estimates for T2D, both overall and in those with CVD. MATERIALS AND METHODS: Using the NHANES 2007-2014 data, we conducted a cross-sectional analysis of an adult sample with diagnosed and undiagnosed T2D, aged ≥18 years. CVD was defined based on self-reported personal interview data on a broad range of health conditions-congestive heart failure, coronary heart disease, angina, stroke, or heart attack. T2D was defined as diagnosed T2D (self-reported provider diagnosis) and undiagnosed T2D (FPG ≥126 mg/dL or HbA1c ≥ 6.5% without self-reported diagnosis). Participants who started insulin within a year of T2D diagnosis, or were pregnant at the time of health examination were excluded. Appropriate sample weights were used to provide a national estimate. RESULTS: The prevalence of moderate to severe renal impairment based on eGFR below 60 ml/min/1.73 m2 among T2D was 18.0%. The prevalence of mild renal impairment was 36.9%: 28.3% with UACR<30 mg/g, 7.0% with UACR ≥30-300 mg/g and 1.6% with UACR >300 mg/g. For T2D and CVD subgroup, the prevalence was 33.6% for moderate to severe renal impairment and 42.8% for mild renal impairment. CONCLUSIONS: This study confirms the high prevalence of CKD in patients with multiple comorbidities: T2D and CVD. It also provides estimates of the prevalence of CKD categories based on KDIGO 2012 classification for US adults with T2D.

Non-herbal tea consumption and ovarian cancer risk: a systematic review and meta-analysis of observational epidemiologic studies with indirect comparison and dose-response analysis.

Ovarian cancer (OC) accounts for 4% of female malignancies worldwide, and its prognosis is unfavorable. Currently available epidemiologic data suggest that non-herbal tea consumption may reduce OC risk, but these evidences are inconsistent. A comprehensive literature search for observational epidemiologic studies reporting associations between non-herbal tea consumption and OC risk was conducted in electronic databases. A random-effects model was used to synthesize effect measures in binary meta-analysis, and adjusted indirect comparison was used to compare whether there was a difference in effects between green tea (GT) and black tea (BT). Both linear and non-linear models were used to explore the dose-response relationship. Fourteen studies were included, and we obtained an inverse and significant pooled estimate in binary meta-analysis [risk ratio (RR)pool = 0.76, 95% confidence interval (CI) 0.61-0.95, PCochran < 0.001, I2 = 81.5%]. No publication bias was identified in binary meta-analysis. In binary meta-analysis stratified by tea types, we observed a significant association for GT (RRpool = 0.64, 95% CI 0.45-0.90, PCochran = 0.071, I2 = 53.6%), but not BT (RRpool = 0.85, 95% CI 0.65-1.12, PCochran = 0.007, I2 = 65.9%). Indirect comparison, which treated BT as the reference, showed an inverse but non-significant association (RRGT versus BT = 0.74, 95% CI 0.48-1.15). Both linear and non-linear models found that OC risk decreased as the consumption levels of total non-herbal tea increased. However, the dose-response relationship was stronger for GT when compared with BT. Our results suggest that non-herbal tea, especially GT, is associated with a reduced risk of OC. Future studies should explore biochemical evidence regarding the variation in chemopreventive effects between different types of non-herbal tea.

The association and dose-response relationship between dietary intake of α-linolenic acid and risk of CHD: a systematic review and meta-analysis of cohort studies.

Previous studies show inconsistent associations between α-linolenic acid (ALA) and risk of CHD. We aimed to examine an aggregate association between ALA intake and risk of CHD, and assess for any dose-response relationship. We searched the PubMed, EMBASE and Web of Science databases for prospective cohort studies examining associations between ALA intake and CHD, including composite CHD and fatal CHD. Data were pooled using random-effects meta-analysis models, comparing the highest category of ALA intake with the lowest across studies. Subgroup analysis was conducted based on study design, geographic region, age and sex. For dose-response analyses, we used two-stage random-effects dose-response models. In all, fourteen studies of thirteen cohorts were identified and included in the meta-analysis. The pooled results showed that higher ALA intake was associated with modest reduced risk of composite CHD (risk ratios (RR)=0·91; 95 % CI 0·85, 0·97) and fatal CHD (RR=0·85; 95 % CI 0·75, 0·96). The analysis showed a J-shaped relationship between ALA intake and relative risk of composite CHD (χ 2=21·95, P<0·001). Compared with people without ALA intake, only people with ALA intake <1·4 g/d showed reduced risk of composite CHD. ALA intake was linearly associated with fatal CHD - every 1 g/d increase in ALA intake was associated with a 12 % decrease in fatal CHD risk (95 % CI -0·21, -0·04). Though a higher dietary ALA intake was associated with reduced risk of composite and fatal CHD, the excess composite CHD risk at higher ALA intakes warrants further investigation, especially through randomised controlled trials.

Diabetes mellitus and risk of ovarian cancer. A systematic review and meta-analysis of 15 cohort studies.

AIM: Diabetes mellitus (DM) is hypothesized to be associated with an increased risk of ovarian cancer (OC), but current evidences are inconsistent. We aimed to further study this association. METHODS: PubMed, EMBASE, Web of Science, and Scopus were searched for eligible articles. After descriptive summary of the data, a random-effects model was applied in quantitative synthesis. Subgroup analysis was performed by study locales and settings, and sensitivity analysis was conducted based on restrictive selection criteria. Funnel plots and the Egger's test were used to assess publication bias. Statistical heterogeneity in meta-analysis was assessed by the P value derived from the Cochrane Q statistic and I-squared value. RESULTS: Fourteen articles involving data of 15 cohort studies were included for our research. Overall, 17 risk ratios (RRs) were synthesized and yielded a pooled RR of 1.32 (95%CI: 1.14-1.52, PCochrane<0.001, I2=79.8%). Thirteen RRs were synthesized for type 2DM, and the pooled RR was 1.24 (95%CI: 1.06-1.44, PCochrane<0.001, I2=81.8%). Four RRs were synthesized for type 1DM, and the result was significant (RR: 1.83, 95%CI: 1.21-2.78, PCochrane=0.080, I2=55.7%). Results of sensitivity analysis suggested the robustness of a positive association between DM and OC risk, and subgroup analysis demonstrated that the association between DM and OC was much more substantial among Asia population. No publication bias was identified in meta-analysis. CONCLUSION: Our study suggests there is a moderate relative increase in the risk of OC among DM patients. Future studies should investigate the effect of duration of DM and anti-diabetes intervention to OC risk.

Diabetes mellitus and long-term mortality of ovarian cancer patients. A systematic review and meta-analysis of 12 cohort studies.

Ovarian cancer (OC) is the sixth most common cancer among women, and its prognosis is not favorable. Diabetes mellitus (DM) is hypothesized to be associated with a higher mortality in ovarian cancer patients, but evidence is inconsistent. Thus, we aim to investigate if DM is associated with the long-term all-cause and long-term cancer-specific mortality in ovarian cancer patients by synthesizing available epidemiologic evidences. We used 4 electronic databases (PubMed, EMBASE, Web of Science, and Scopus) to search for eligible articles. Title/abstract screening, full-text review, data extraction, and quality assessment were performed by reviewers independently. In meta-analysis, studies reporting risk ratio (RR) or hazard ratio that investigated the association between DM and mortality of OC patients were synthesized by a random-effect model. Subgroup and sensitivity analyses were performed by certain stratification or restrictive rules. Publication bias was assessed by funnel plots and Egger test. Statistical heterogeneity was evaluated by the I-squared value and a chi-squared test for the Cochrane Q statistic. Twelve cohort studies involving 14 outcome measures were included. In overall meta-analysis, the synthesized RR for all-cause mortality was 1.44 (95% CI 1.16-1.79) without substantial statistical heterogeneity (PCochrane  = .145, I2  = 34.1%); the synthesized RR for cancer-specific mortality was 1.44 (95% CI 1.08-1.93) with substantial heterogeneity (PCochrane  < .001, I2  = 90.1%). No publication bias was observed. Our results suggest DM is associated with a higher all-cause and cancer-specific mortality in ovarian cancer patients. Future studies should be done to examine the association between type 1 DM and ovarian cancer mortality.

Can Aspirin Reduce the Risk of Endometrial Cancer?: A Systematic Review and Meta-analysis of Observational Studies.

Current evidences suggest that nonsteroidal anti-inflammatory drugs can reduce the risk of several types of cancer, including breast, prostate, and colorectal cancer. However, evidences regarding the chemopreventive effect of aspirin to endometrial cancer are inconsistent. Therefore, we aimed to further explore the association. We searched PubMed, EMBASE, Web of Science, and Scopus to identify potentially eligible studies. After title/abstract screening and full-text review, we identified 7 cohort studies and 6 case-control studies. Data extraction and quality assessment were performed independently, and a random-effects model was used for data synthesis. Subgroup analysis was conducted based on obesity, hormone replacement therapy use, and cancer subtype; sensitivity analysis was conducted by pooling risk ratios of the highest dosage or longest duration of use. Dose-response relationship was assessed by a 2-stage linear dose-response model. Statistical heterogeneity was assessed by the I value and a χ test for the Cochrane Q statistic. In overall meta-analysis, the pooled risk ratio was 0.93 (95% confidence interval, 0.88-0.99), and no substantial statistical heterogeneity was observed (I = 0.0%, P = 0.550). In subgroup analysis, a negative association was observed for obese women and type I endometrial cancer. Higher dosage or frequency of aspirin use was significantly associated with a reduced risk, and long-term aspirin use was protective only for obese women. In conclusion, our study suggests that the use of aspirin can reduce the risk of endometrial cancer, particularly for obese women. However, the generalizability of our conclusion should be further studied for premenopausal women and type II endometrial cancer.

Is aspirin use associated with a decreased risk of ovarian cancer? A systematic review and meta-analysis of observational studies with dose-response analysis.

OBJECTIVE: Currently available epidemiologic evidences concerning the chemopreventive effect of aspirin on ovarian cancer are inconsistent. Therefore, we aimed to further explore the association by synthesizing evidence from population-based studies. METHODS: We searched PubMed, EMBASE, Web of Science, and Scopus using key words and controlled vocabularies. Title/abstract screening, full-text review, data extraction, and quality assessment were performed independently by reviewers, and a random-effects model was utilized for meta-analysis. Subgroup analysis was conducted based on study locale, and sensitivity analysis was performed by synthesizing studies that adjusted for certain covariates or studies with good quality. Dose-response relation was assessed by a two-stage linear dose-response model. Statistical heterogeneity was evaluated by the I-squared value and a chi-squared test for the Cochrane Q statistic. RESULTS: We identified 8 cohort studies and 15 case-control studies. In overall meta-analysis of risk ratios (RRs) of binary exposure, the synthesized RR was 0.89 (95% CI, 0.83-0.96), and no substantial statistical heterogeneity was observed (I(2)=22.5%, PCochrane=0.168). After stratification by study design, the synthesized RR was 0.85 (95% CI, 0.77-0.94) and 0.95 (95% CI, 0.85-1.05) for case-control and cohort studies, respectively. In sensitivity analysis, the synthesized estimate of long-term use was not statistically significant, whereas the effect measure (RRmeta=0.60, 95% CI, 0.39-0.93) was significant by synthesizing RRs of the highest frequency of use from 2 cohort studies. The dose-response analysis showed an inverse significant association between aspirin use and the risk (RRper 1time/wk=0.94, 95% CI, 0.89-1.00; n=2). Egger's tests showed that publication bias existed for overall meta-analysis, meta-analysis for case-control studies, and studies conducted in the United States. CONCLUSION: In summary, our study suggests that aspirin can reduce the risk of ovarian cancer. In addition, we observed a possible dose-response relation between frequency of use and ovarian cancer risk, but further studies are needed to examine this association.