Trends in cigarette smoking and the risk of incident cardiovascular disease among Asian American, Pacific Islander, and multiracial populations.

Background: Cardiovascular disease (CVD) is the leading cause of death in the United States, and rates of CVD incidence vary widely by race and ethnicity. Cigarette smoking is associated with increased risk of CVD. The purpose of the study was: 1) to examine smoking prevalence over time across Asian and Pacific Islander (API) and multi-race API subgroups; 2) to determine whether the CVD risk associated with smoking differed among these subgroups. Methods: We identified patients belonging to 7 single race/ethnicity groups, 4 multi-race/ethnicity groups, and a non-Hispanic White (NHW) comparison group at two large health systems in Hawaii and California. We estimated annual smoking prevalence from 2011 through 2018 by group and gender. We examined incidence of CVD events by smoking status and race/ethnicity, and computed hazard ratios for CVD events by age, gender, race/ethnicity, census block median household income, census block college degree, and study site using Cox regression. Results: Of the 12 groups studied, the Asian Indian and Chinese American groups had the lowest smoking prevalence, and the Asian + Pacific Islander multiracial group had the highest smoking prevalence. The prevalence of smoking decreased from 2011 to 2018 for all groups. Multi-race/ethnicity groups had higher risk of CVD than the NHW group. There was no significant interaction between race/ethnicity and smoking in models predicting CVD, but the association between race/ethnicity and CVD incidence was attenuated after adjusting for smoking status. Conclusions: There is considerable heterogeneity in smoking prevalence and the risk of CVD among API subgroups.

Age at lung cancer diagnosis in females versus males who never smoke by race and ethnicity.

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke. METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes. RESULTS: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = -2.2 (95% confidence interval (CI):-2.5, -1.9), in Shanghai (n = 1049) (Δ years = -1.6 (95% CI:-2.9, -0.3), and in Sutter Health and Kaiser Permanente Hawai'i in the US (n = 82) (Δ years = -11.3 (95% CI: -17.7, -4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant. CONCLUSIONS: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke.

Suicide attempts after bariatric surgery: comparison to a nonsurgical cohort of individuals with severe obesity.

BACKGROUND: The rate of suicide is higher among individuals following bariatric surgery compared with the general population; however, it is not clear whether risk is associated with bariatric surgery beyond having severe obesity. OBJECTIVE: To compare the risk of a suicide attempt among those who had bariatric surgery versus a nonsurgical cohort with severe obesity. SETTING: Aggregate count data were collected from 5 healthcare systems. METHODS: Individuals were identified in the surgical cohort if they underwent bariatric surgery between 2009 and 2017 (n = 35,522) and then were compared with a cohort of individuals with severe obesity who never had bariatric surgery (n = 691,752). Suicide attempts were identified after study enrollment date using International Classification of Diseases, Ninth and Tenth Editions (ICD-9 and ICD-10) diagnosis codes from 2009 to 2021. RESULTS: The relative risk of a suicide attempt was 64% higher in the cohort with bariatric surgery than that of the nonsurgical cohort (2.2% versus 1.3%; relative risk = 1.64; 95% CI, 1.53-1.76). Within the cohort with bariatric surgery, suicide attempts were more common among the 18- to 39-year age group (P < .001), women (P = .002), Hawaiian-Pacific Islanders (P < .001), those with Medicaid insurance (P < .001), and those with a documented mental health condition at baseline (in the previous 2 years; P < .001). CONCLUSIONS: The relative risk of suicide attempts was higher among those who underwent bariatric surgery compared with a nonsurgical cohort, though absolute risk remained low. Providers should be aware of this increased risk. Screening for suicide risk after bariatric surgery may be useful to identify high-risk individuals.

Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C.

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.

Impact of hepatitis C treatment status on risk of Parkinson's disease and secondary parkinsonism in the era of direct-acting antivirals.

Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75-5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31-3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22-0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors-diabetes, cirrhosis and BMI-were associated with PD/PKM.

Cancer and psychiatric diagnoses in the year preceding suicide.

BACKGROUND: Patients with cancer are known to be at increased risk for suicide but little is known about the interaction between cancer and psychiatric diagnoses, another well-documented risk factor. METHODS: Electronic medical records from nine healthcare systems participating in the Mental Health Research Network were aggregated to form a retrospective case-control study, with ICD-9 codes used to identify diagnoses in the 1 year prior to death by suicide for cases (N = 3330) or matching index date for controls (N = 297,034). Conditional logistic regression was used to assess differences in cancer and psychiatric diagnoses between cases and controls, controlling for sex and age. RESULTS: Among patients without concurrent psychiatric diagnoses, cancer at disease sites with lower average 5-year survival rates were associated with significantly greater relative risk, while cancer disease sites with survival rates of >70% conferred no increased risk. Patients with most psychiatric diagnoses were at higher risk, however, there was no additional risk conferred to these patients by a concurrent cancer diagnosis. CONCLUSION: We found no evidence of a synergistic effect between cancer and psychiatric diagnoses. However, cancer patients with a concurrent psychiatric illness remain at the highest relative risk for suicide, regardless of cancer disease site, due to strong independent associations between psychiatric diagnoses and suicide. For patients without a concurrent psychiatric illness, cancer disease sites associated with worse prognoses appeared to confer greater suicide risk.

Detecting and distinguishing indicators of risk for suicide using clinical records.

Health systems are essential for suicide risk detection. Most efforts target people with mental health (MH) diagnoses, but this only represents half of the people who die by suicide. This study seeks to discover and validate health indicators of suicide death among those with, and without, MH diagnoses. This case-control study used statistical modeling with health record data on diagnoses, procedures, and encounters. The study included 3,195 individuals who died by suicide from 2000 to 2015 and 249,092 randomly selected matched controls, who were age 18+ and affiliated with nine Mental Health Research Network affiliated health systems. Of the 202 indicators studied, 170 (84%) were associated with suicide in the discovery cohort, with 148 (86%) of those in the validation cohort. Malignant cancer diagnoses were risk factors for suicide in those without MH diagnoses, and multiple individual psychiatric-related indicators were unique to the MH subgroup. Protective effects across MH-stratified models included diagnoses of benign neoplasms, respiratory infections, and utilization of reproductive services. MH-stratified latent class models validated five subgroups with distinct patterns of indicators in both those with and without MH. The highest risk groups were characterized via high utilization with multiple healthcare concerns in both groups. The lowest risk groups were characterized as predominantly young, female, and high utilizers of preventive services. Healthcare data include many indicators of suicide risk for those with and without MH diagnoses, which may be used to support the identification and understanding of risk as well as targeting of prevention in health systems.

Incidence of Malignancies Among Patients With Chronic Hepatitis B in US Health Care Organizations, 2006-2018.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Trends in Cirrhosis and Mortality by Age, Sex, Race, and Antiviral Treatment Status Among US Chronic Hepatitis B Patients (2006-2016).

BACKGROUND: Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS: Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS: Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS: From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.

Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States.

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with 'definite' indications for antiviral therapy remained untreated.

Incidence of Lung Cancer Among Never-Smoking Asian American, Native Hawaiian, and Pacific Islander Females.

BACKGROUND: Although lung cancer incidence rates according to smoking status, sex, and detailed race/ethnicity have not been available, it is estimated that more than half of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. METHODS: We calculated age-adjusted incidence rates for lung cancer according to smoking status and detailed race/ethnicity among females, focusing on AANHPI ethnic groups, and assessed relative incidence across racial/ethnic groups. We used a large-scale dataset that integrates data from electronic health records from 2 large health-care systems-Sutter Health in Northern California and Kaiser Permanente Hawai'i-linked to state cancer registries for incident lung cancer diagnoses between 2000 and 2013. The study population included 1 222 694 females (n = 244 147 AANHPI), 3297 of which were diagnosed with lung cancer (n = 535 AANHPI). RESULTS: Incidence of lung cancer among never-smoking AANHPI as an aggregate group was 17.1 per 100 000 (95% confidence interval [CI] = 14.9 to 19.4) but varied widely across ethnic groups. Never-smoking Chinese American females had the highest rate (22.8 per 100 000, 95% CI = 17.3 to 29.1). Except for Japanese American females, incidence among every never-smoking AANHPI female ethnic group was higher than that of never-smoking non-Hispanic White females, from 66% greater among Native Hawaiian females (incidence rate ratio = 1.66, 95% CI = 1.03 to 2.56) to more than 100% greater among Chinese American females (incidence rate ratio = 2.26, 95% CI = 1.67 to 3.02). CONCLUSIONS: Our study revealed high rates of lung cancer among most never-smoking AANHPI female ethnic groups. Our approach illustrates the use of innovative data integration to dispel the myth that AANHPI females are at overall reduced risk of lung cancer and demonstrates the need to disaggregate this highly diverse population.

Integrating Electronic Health Record, Cancer Registry, and Geospatial Data to Study Lung Cancer in Asian American, Native Hawaiian, and Pacific Islander Ethnic Groups.

BACKGROUND: A relatively high proportion of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. We used an integrative data approach to assemble a large-scale cohort to study lung cancer risk among AANHPIs by smoking status with attention to representation of specific AANHPI ethnic groups. METHODS: We leveraged electronic health records (EHRs) from two healthcare systems-Sutter Health in northern California and Kaiser Permanente Hawai'i-that have high representation of AANHPI populations. We linked EHR data on lung cancer risk factors (i.e., smoking, lung diseases, infections, reproductive factors, and body size) to data on incident lung cancer diagnoses from statewide population-based cancer registries of California and Hawai'i for the period between 2000 and 2013. Geocoded address data were linked to data on neighborhood contextual factors and regional air pollutants. RESULTS: The dataset comprises over 2.2 million adult females and males of any race/ethnicity. Over 250,000 are AANHPI females (19.6% of the female study population). Smoking status is available for over 95% of individuals. The dataset includes 7,274 lung cancer cases, including 613 cases among AANHPI females. Prevalence of never-smoking status varied greatly among AANHPI females with incident lung cancer, from 85.7% among Asian Indian to 14.4% among Native Hawaiian females. CONCLUSION: We have developed a large, multilevel dataset particularly well-suited to conduct prospective studies of lung cancer risk among AANHPI females who never smoked. IMPACT: The integrative data approach is an effective way to conduct cancer research assessing multilevel factors on cancer outcomes among small populations.

The Persistence of Underreporting of Hepatitis C as an Underlying or Contributing Cause of Death, 2011-2017.

Using electronic health records, we found that hepatitis C virus (HCV) reporting on death certificates of 2901 HCV-infected decedents from 4 US healthcare organizations during 2011-2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the US HCV mortality burden.

Validity of an Automated Algorithm to Identify Cirrhosis Using Electronic Health Records in Patients with Primary Biliary Cholangitis.

BACKGROUND: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients. METHODS: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis. RESULTS: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively). CONCLUSION: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

Trends in Diagnosed Chronic Hepatitis B in a US Health System Population, 2006-2015.

BACKGROUND: Trends in the epidemiology of chronic hepatitis B (CHB) among routine clinical care patients in the United States are not well documented. We used data from the Chronic Hepatitis Cohort Study to investigate changes in prevalence and newly recorded cases of CHB from 2006 to 2015. METHODS: Annual percentage changes (APCs) were estimated using join point Poisson regression. Analyses were adjusted by study site; when an interaction with the trend was observed, APCs were estimated by subgroups. Differences in rates based on race, age, and sex were calculated with rate ratios. RESULTS: We identified 5492 patients with CHB within select health systems with total populations that ranged from 1.9 to 2.4 million persons. From 2006 to 2014, the prevalence of diagnosed CHB increased from 181.3 to 253.0 per 100 000 persons in the health system population; from 2014 to 2015, it declined to 237.0 per 100 000 persons. APC was +3.7%/y through 131 December 2014 (P < .001) and -15.0%/y (P < .001) thereafter. The rate of newly reported cases of CHB did not change significantly across the study period (APC, -1.1%/y; P = .07). The rates of newly reported cases were 20.5 times higher among patients in the Asian American/American Indian/Pacific Islander (ASINPI) category, compared with white patients, and 2.8 times higher among African American patients. The ratio of male to female patients was roughly 3:2. CONCLUSIONS: The prevalence of diagnosed CHB in this US patient population increased from 2006 to 2014, after which it decreased significantly. Rates declined most rapidly among patients ≤40 or 61-70 years old, as well as among ASINPI patients. The rate of newly reported cases remained steady over the study period.

Mortality Among Patients With Chronic Hepatitis B Infection: The Chronic Hepatitis Cohort Study (CHeCS).

BACKGROUND: According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). METHODS: We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. RESULTS: Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P < .001). CHB patients died at an average age of 59.8 years-14 years younger than the general U.S. population-and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851-1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81-16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. CONCLUSIONS: Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB.

Adolescent dairy consumption and physical activity associated with bone mass.

BACKGROUND: This study identifies key modifiable factors influencing Asian and White adolescent bone development. Cross-sectional analysis of baseline data of cohort. METHODS: Three hundred and twenty-three girls were examined from age-eligible girls at Kaiser Permanente Oahu in Hawaii. Girls' age, ethnicity, Tanner stage, 3-day diet record, level of physical activity, anthropometry, and calcaneal bone status were obtained by questionnaire and measurement, respectively. Lunar Achilles calcaneal was used to measure calcaneal bone mass. Multiple regression was used for analysis of factors influencing bone mass. RESULTS: The mean age of adolescents was 11.6 +/- 1.5 years. Girls were generally ethnically mixed; the mean Asian ethnic proportion was 48% while White ethnic proportion was 43% and other ethnic proportion was 10%. Multiple regression explained 40.8% and 25.6% of the variation in calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS), respectively, in a model where age, weight, biacromial breadth, Tanner pubic hair stage, Asian ethnicity, dairy intake, and physical activity positively influenced bone mass. CONCLUSIONS: Tanner pubic hair stage, ethnicity, and biacromial breadth had the greatest influence on SOS; while physical activity, body weight, and dairy product intake had the greatest influence on BUA.