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Open Access Publications from the University of California

Scholarly Works (12 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2017)

Background: Liver cancer is the second most fatal cancer in the world. China is disproportionally affected, accounting for approximately 50% of liver cancer cases and deaths worldwide. Major risk factors for liver cancer include chronic hepatitis B and C viral infections, aflatoxin B1 exposure, alcoholic consumption, and tobacco smoking. Objective and Methods: We aimed to update the fraction of liver cancer cases attributable to these known risk factors, as well as estimate attributable risk of obesity for liver cancer at country, regional, and global levels. At the individual level, a population-based case-control study was conducted in a high risk area of China, Jiangsu Province, to evaluate novel associations between dietary intakes of flavonoids as well as glycemic index and load with liver cancer, and to assess original relationships of single nucleotide polymorphisms (SNPs) of NF-κB, the stem cell pathway, and GWAS SNPs with liver cancer. The association between SNPs and liver cancer was additionally stratified by flavonoid intake. Results: In the global analyses, we found that most liver cancer cases could be attributed to viral hepatitis, particularly in low income regions. Alcohol consumption was the strongest lifestyle risk factor, and patterns varied geographically. In the case-control study, we observed marginal and inverse associations between total flavonoid consumption and liver cancer, driven in largely by the protective association between tea consumption and liver cancer. Carbohydrate intake was associated with increased odds of liver cancer. No obvious association between SNPs of the NF-κB pathway and liver cancer was observed, however, genetic risk scores of SNPs of the stem cell pathway and those identified in GWAS studies were associated with liver cancer. Furthermore, we found that dietary flavonoid intake modified the associations between liver cancer and selected SNPs. Conclusion: This study provides policy-makers updated and regionally specific estimates of the burden of cancer. The results from the case-control study support a marginally protective effect of dietary flavonoid consumption, and a marginal increase in susceptibility associated with increased glycemic load and liver cancer in a Chinese population. Furthermore, there was evidence that dietary intake may modify the associations between some SNPs and liver cancer.

    Cover page: Geographic Variability and the Association of Flavonoids, Glycemic Index, and Related Single Nucleotide Polymorphisms with Liver Cancer
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2018)
    To facilitate regionally specific liver cancer prevention and control, this study estimates the fraction of hepatocellular carcinoma (HCC) cases attributable to five major liver cancer risk factors by geographic region. Prevalence estimates of major HCC risk factors, including chronic infection with hepatitis B and hepatitis C, alcohol drinking, tobacco smoking, obesity, and diabetes, were extracted for each country from the literature, along with recent incidence and risk estimate data, to calculate regionally specific population attributable fractions. Overall, 44% of HCC cases worldwide were attributable to chronic hepatitis B infection, with the majority of cases occurring in Asia. Hepatitis C was responsible for 21% of cases. Lifestyle risk factors such as alcohol drinking and obesity were responsible for a larger percentage of cases in North America and Western, Central, and Eastern Europe. In addition, strong sex disparities were observed when looking at lifestyle risk factors, particularly tobacco smoking, in Asia and Africa. Prominent risk factors for HCC vary depending on the region. Our findings provide useful data for developing regionally specific guidelines for liver cancer prevention and control worldwide.
      Cover page: Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2023)

      Introduction

      Physical activity before COVID-19 infection is associated with less severe outcomes. The study determined whether a dose‒response association was observed and whether the associations were consistent across demographic subgroups and chronic conditions.

      Methods

      A retrospective cohort study of Kaiser Permanente Southern California adult patients who had a positive COVID-19 diagnosis between January 1, 2020 and May 31, 2021 was created. The exposure was the median of at least 3 physical activity self-reports before diagnosis. Patients were categorized as follows: always inactive, all assessments at 10 minutes/week or less; mostly inactive, median of 0-60 minutes per week; some activity, median of 60-150 minutes per week; consistently active, median>150 minutes per week; and always active, all assessments>150 minutes per week. Outcomes were hospitalization, deterioration event, or death 90 days after a COVID-19 diagnosis. Data were analyzed in 2022.

      Results

      Of 194,191 adults with COVID-19 infection, 6.3% were hospitalized, 3.1% experienced a deterioration event, and 2.8% died within 90 days. Dose‒response effects were strong; for example, patients in the some activity category had higher odds of hospitalization (OR=1.43; 95% CI=1.26, 1.63), deterioration (OR=1.83; 95% CI=1.49, 2.25), and death (OR=1.92; 95% CI=1.48, 2.49) than those in the always active category. Results were generally consistent across sex, race and ethnicity, age, and BMI categories and for patients with cardiovascular disease or hypertension.

      Conclusions

      There were protective associations of physical activity for adverse COVID-19 outcomes across demographic and clinical characteristics. Public health leaders should add physical activity to pandemic control strategies.
        Cover page: Associations of Physical Inactivity and COVID-19 Outcomes Among Subgroups
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2019)

        Background and objective

        Early detection methods for pancreatic cancer are lacking. We aimed to develop a prediction model for pancreatic cancer based on changes in health captured by healthcare claims data.

        Methods

        We conducted a case-control study on 29,646 Medicare-enrolled patients aged 68 years and above with pancreatic ductal adenocarcinoma (PDAC) reported to the Surveillance Epidemiology an End Results (SEER) tumor registries program in 2004-2011 and 88,938 age and sex-matched controls. We developed a prediction model using multivariable logistic regression on Medicare claims for 16 risk factors and pre-diagnostic symptoms of PDAC present within 15 months prior to PDAC diagnosis. Claims within 3 months of PDAC diagnosis were excluded in sensitivity analyses. We evaluated the discriminatory power of the model with the area under the receiver operating curve (AUC) and performed cross-validation by bootstrapping.

        Results

        The prediction model on all cases and controls reached AUC of 0.68. Excluding the final 3 months of claims lowered the AUC to 0.58. Among new-onset diabetes patients, the prediction model reached AUC of 0.73, which decreased to 0.63 when claims from the final 3 months were excluded. Performance measures of the prediction models was confirmed by internal validation using the bootstrap method.

        Conclusion

        Models based on healthcare claims for clinical risk factors, symptoms and signs of pancreatic cancer are limited in classifying those who go on to diagnosis of pancreatic cancer and those who do not, especially when excluding claims that immediately precede the diagnosis of PDAC.
          Cover page: Do changes in health reveal the possibility of undiagnosed pancreatic cancer? Development of a risk-prediction model based on healthcare claims data
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2022)

          Objective

          Describe emergency department (ED) management and patient outcomes for febrile infants 29-60 days of age who received a lumbar puncture (LP), with focus on timing of antibiotics and type of physician performing LP.

          Methods

          Retrospective observational study of 35 California EDs from January 1, 2010 through December 31, 2019. Primary analysis was among patients with successful LP and primary outcome was hospital length of stay (LOS). Logistic regression analysis included variables associated with LOS of at least 2 days. Secondary outcomes were bacterial meningitis, hospital admission, length of antibiotics, and readmission.

          Results

          Among 2569 febrile infants (median age 39 days), 667 underwent successful LP and 633 received intravenous antibiotics. Most infants (n = 559, 88.3%) had their LP before intravenous antibiotic administration. Pediatricians performed 54% of LPs and emergency physicians 34%. Sixteen infants (0.6% of 2569) were diagnosed with bacterial meningitis, and none died. Five hundred and fifty-eight (88%) infants receiving an LP were hospitalized. Among patients receiving an LP and antibiotics (n = 633), 6.5% were readmitted within 30 days. Patients receiving antibiotics before LP had a longer length of antibiotics (+ 7.9 hours, 95% confidence interval [CI] 3.8-13.4). Primary analysis found no association between timing of antibiotics and LOS (odds ratio [OR] 0.67, 95% CI 0.34-1.30), but shorter LOS when emergency physicians performed the LP (OR 0.66, 95% CI 0.45-0.97).

          Conclusions

          Febrile infants in the ED had no deaths and few cases of bacterial meningitis. In community EDs, where a pediatrician is often not available, successful LP by emergency physician was associated with reduced inpatient LOS.
            Creative Commons 'BY-NC-ND' version 4.0 license
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2019)

            Background & aims

            Although non-alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known.

            Methods

            A population-based cohort of adult CHB patients without a history of alcohol drinking or NAFLD were recruited and followed up from October 2012 to January 2015 in Jiangsu province, China. Using Cox proportional hazards regression model, potential risk factors including viral and metabolic factors for NAFLD were evaluated.

            Results

            Two thousand three hundred and ninety-three adult CHB patients (mean age 50.7 ± 13.2 years) were included in the cohort. With 4429 person-years of follow-up, 283 individuals progressed to NAFLD with an incidence rate of 63.89/1000 person-years. Overweight and obese CHB patients had an increased risk of NAFLD (overweight adjusted hazard ratio [HR], 3.10; 95% CI, 2.29-4.18; obese HR, 8.52; 95%CI, 5.93-12.25) compared to normal weight carriers. The incidence of NAFLD was associated with concurrent type 2 diabetes mellitus (DM) (HR, 1.88; 95%CI, 1.15-3.08). However, no associations between viral factors with NAFLD incidence rate were identified. In a subgroup of participants with concurrent type 2 DM, detectable HBV DNA levels were negatively associated with the development of NAFLD (HR, 0.37; 95%CI, 0.14-0.98). There was super-multiplicative interaction between BMI and gender with respect to incidence of NAFLD, with an ROR of 2.08 (95%CI, 1.02-4.23).

            Conclusion

            Metabolic factors play an important role in the presence of NAFLD among Chinese CHB patients. However, viral replication factors are not related to NAFLD except among those with concurrent type 2 DM.
              Cover page: Hepatitis B virus infection and risk of non‐alcoholic fatty liver disease: A population‐based cohort study
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2020)

              Objective

              We sought to identify sub-groups of "low-risk" HEART score patients (history, ECG, age, risk factors, and troponin) at elevated risk of acute myocardial infarction or death within 30 days.

              Methods

              We performed a secondary analysis of prospective emergency department (ED) encounters for suspected acute coronary syndrome in a large health system with low-risk HEART scores (0-5 points). Logistic regression using the 5 components of the HEART score analyzed the increase risk attributable to points from each of the 5 score components.

              Results

              Of 30,971 encounters among 28,992 unique patients, 135 (0.44%, 95% confidence interval [CI] = 0.37-0.51) experienced acute myocardial infarction or death. Risk increased for each component of the HEART score from 0 to 1 to 2 points (history, 0.4% to 0.5% to 0.6%; ECG, 0.3% to 0.7% to 0.7%; age, 0.2% to 0.3% to 0.7%; risk factors, 0.1% to 0.4% to 0.8%), except troponin, which had the highest risk with 1 point (troponin, 0.4% to 2.7% to 0.9%). Odds ratios from our regression, which adjusts for other components, showed a similar pattern (from 1 vs 0 and 2 vs 0 points, respectively: history, 1.0 and 1.8; ECG, 2.2 and 3.5; age, 1.2 and 2.1; risk factors, 2.4 and 4.2; and troponin, 6.0 and 3.6).

              Conclusion

              Among "low-risk" suspected acute coronary syndrome encounters, increasing points within each of the 5 categories demonstrated small increases in risk of death or acute myocardial infarction, with the troponin and ECG components representing the largest risk increases.
                Cover page: Not all HEART scores are created equal: identifying “low‐risk” patients at higher riskCreative Commons 'BY-NC-SA' version 4.0 license
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2021)

                Study objective

                We compare clinical management and outcomes of emergency department (ED) encounters by sex after implementation of a clinical care pathway in 15 community EDs that standardized recommendations based on patient risk, using the History, ECG, Age, Risk Factors, and Troponin (HEART) score.

                Methods

                This was a retrospective analysis of adult ED encounters evaluated for suspected acute coronary syndrome with a documented HEART score from May 20, 2016, to December 1, 2017. The primary outcomes were hospitalization or 30-day stress testing. Secondary outcomes included 30-day acute myocardial infarction or all-cause death (major adverse cardiac event). A generalized estimating equation regression model was used to compare the odds of hospitalization or stress testing by sex; we report HEART scores (0 to 10) stratified by sex and describing major adverse cardiac events.

                Results

                A total of 34,715 adult ED encounters met the inclusion criteria (56.0% women). A higher proportion of women were classified as low risk (60.5% versus 52.4%; odds ratio [OR] 1.39; 95% confidence interval [CI] 1.33 to 1.45). Women were hospitalized or received stress testing less frequently than men for low HEART scores (18.8% versus 22.8%; OR 0.79; 95% CI 0.73 to 0.84) and intermediate ones (46.7% versus 49.7%; OR 0.88; 95% CI 0.83 to 0.95), but similarly for high-risk ones (74.1% versus 74.4%; OR 0.99; 95% CI 0.77 to 1.28). Women had 18% lower odds of hospitalization or noninvasive cardiac testing (OR 0.82; 95% CI 0.78 to 0.86), even after adjusting for HEART score and comorbidities. Men had higher risks of major adverse cardiac events than women for all HEART score categories but the risk for men was significantly higher among low-risk HEART scores (0.4% versus 0.1%).

                Conclusion

                Women with low-risk HEART scores are hospitalized or stress tested less than men, which is likely appropriate, and women have better outcomes than men. Use of the HEART score has the potential to reduce sex disparities in acute coronary syndrome care.
                  Cover page: Evaluating Sex Disparities in the Emergency Department Management of Patients With Suspected Acute Coronary Syndrome
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2014)
                  One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway.
                    Cover page: Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2019)
                    Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population.
                      Cover page: Raw Garlic Consumption and Risk of Liver Cancer: A Population-Based Case-Control Study in Eastern China
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