All-Cause Mortality and Progression Risks to Hepatic Decompensation and Hepatocellular Carcinoma in Patients Infected With Hepatitis C Virus.

BACKGROUND: A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. METHODS: This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. RESULTS: Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. CONCLUSIONS: The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease.

Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection.

BACKGROUND & AIMS: Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period. METHODS: We collected data from participants in the Chronic Hepatitis Cohort Study-a large observational multicenter study of patients with hepatitis at 4 US health systems-from January 1, 2006, through December 31, 2013. We calculated patients' FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR. RESULTS: In propensity score-adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P < .001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P < .01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score. CONCLUSIONS: SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores.

Predictors of poor mental and physical health status among patients with chronic hepatitis C infection: the Chronic Hepatitis Cohort Study (CHeCS).

UNLABELLED: Our objective was to assess the extent and risk factors for depression and poor physical health among patients with chronic hepatitis C virus (HCV) infection. We surveyed HCV-infected patients seen at four large healthcare systems participating in the Chronic Hepatitis Cohort Study (CHeCS). Survey data included demographics, depression and physical health measures, substance use history, current social support, recent stressor exposures, and, from the electronic medical record, treatment history, and Charlson Comorbidity Index scores. There were 4,781 respondents, who were a mean of 56.7 years old, 71% White, and 57% male. Altogether, 51.4% reported past injection drug use, 33.9% were current smokers, and 17.7% had abused alcohol in the previous year. Additionally, 47.4% had been previously treated for HCV and 14.8% had a 12-week sustained viral response (SVR) following HCV therapy. Overall, 29.7% of patients met criteria for current depression and 24.6% were in poor physical health. In multivariate analyses, significant predictors of depression and poor health included: male gender (versus female, odds ratios [ORs], 0.70 and 0.81), Black race (versus white, ORs, 0.60 and 0.61), having education less than high school (versus college, ORs, 1.81 and 1.54), being employed (versus not, ORs, 0.36 and 0.25), having high life stressors (versus low, ORs, 2.44 and 1.64), having low social support (versus high, ORs=2.78 and 1.40), and having high Charlson scores (versus none, ORs=1.58 and 2.12). Achieving a 12-week SVR was found to be protective for depression. CONCLUSION: This large survey of U.S. HCV patients indicates the extent of adverse health behaviors and mental and physical comorbidities among these patients.

Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort Study (CHeCS): Missed opportunities for intervention.

UNLABELLED: To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis-defined by liver biopsy or mean FIB-4 score >5.88-and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for "late diagnosis" with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. CONCLUSION: Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality.

Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort.

BACKGROUND: Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. METHODS: We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. RESULTS: Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. CONCLUSIONS: Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population.

Prevalence of cirrhosis in hepatitis C patients in the Chronic Hepatitis Cohort Study (CHeCS): a retrospective and prospective observational study.

OBJECTIVES: The severity of liver disease in the hepatitis C virus (HCV)-infected population in the United States remains uncertain. We estimated the prevalence of cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters including liver biopsy, diagnosis/procedure codes, and a biomarker. METHODS: Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received health services during 2006-2010 were included. Cirrhosis was identified through liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic decompensation, and Fibrosis-4 (FIB-4) scores ≥5.88. Demographic and clinical characteristics associated with cirrhosis were identified through multivariable logistic modeling. RESULTS: Among 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%) patients, whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%) patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only 356 (54%) had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender, Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes, history of antiviral therapy, and history of alcohol abuse were independently associated with higher odds of cirrhosis (all, P<0.05). Conversely, private health insurance coverage, black race, and HCV genotype 2 were associated with lower odds of cirrhosis. CONCLUSIONS: A high proportion of patients with biopsy-confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD-9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis in cohort studies. Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.

Trends in HCV RNA testing among HCV antibody-positive persons in care, 2003-2010.

BACKGROUND: A test for hepatitis C virus (HCV) RNA is essential to identify persons with active, or current, HCV infection. We assessed trends in HCV RNA testing following a positive HCV antibody result among persons in 4 large healthcare organizations. METHODS: Data collected from adults with ≥2 clinical encounters during 2003-2010 were analyzed to determine the frequency of, interval between, and factors associated with having an RNA test after a first positive HCV antibody test. RESULTS: From 2003-2010, 5860 persons had a positive antibody test, of whom 3570 (60.9%) had a follow-up RNA test. During this period, the annual frequency of persons with an eventual RNA test did not change significantly; however, the fraction of persons who had the follow-up RNA test within 6 months improved significantly, from 45% in 2003 to 57% in 2010 (P < .001, for trend). Persons born during 1945-1965, men, and those with annual income <$30 000 (by census geocode) were less likely to have had a follow-up RNA test done within 6 months of a positive antibody test. CONCLUSIONS: Less than two-thirds of persons with a positive HCV antibody test had a follow-up RNA test. Rapid ascertainment of HCV infection status with reflex testing to RNA is critical to identify persons eligible for treatment.

Antiviral therapy for chronic hepatitis B virus infection and development of hepatocellular carcinoma in a US population.

BACKGROUND & AIMS: Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers. METHODS: We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence. RESULTS: Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL. CONCLUSIONS: In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC.

Comparative effectiveness research of chronic hepatitis B and C cohort study (CHeCS): improving data collection and cohort identification.

BACKGROUND AND AIMS: The Chronic Hepatitis Cohort Study (CHeCS) is a longitudinal observational study of risks and benefits of treatments and care in patients with chronic hepatitis B (HBV) and C (HCV) infection from four US health systems. We hypothesized that comparative effectiveness methods-including a centralized data management system and an adaptive approach for cohort selection-would improve cohort selection while controlling data quality and reducing the cost. METHODS: Cohort selection and data collection were performed primarily via the electronic health record (EHR); cases were confirmed via chart abstraction. Two parallel sources fed data to a centralized data management system: direct EHR data collection with common data elements, and chart abstraction via electronic data capture. An adaptive Classification and Regression Tree (CART) identified a set of electronic variables to improve case ascertainment accuracy. RESULTS: Over 16 million patient records were collected on 23 case report forms in 2006-2008. The vast majority of data (99.2%) were collected electronically from EHR; only 0.8% was collected via chart abstraction. Initial electronic criteria identified 12,144 chronic hepatitis patients; 10,098 were confirmed via chart abstraction with positive predictive values (PPV) 79 and 83% for HBV and HCV, respectively. CART-optimized models significantly increased PPV to 88 for HBV and 95% for HCV. CONCLUSIONS: CHeCS is a comparative effectiveness research project that leverages electronic centralized data collection and adaptive cohort identification approaches to enhance study efficiency. The adaptive CART model significantly improved the positive predictive value of cohort identification methods.

Risk factors for hepatitis C infection among Vietnam era veterans versus nonveterans: results from the Chronic Hepatitis Cohort Study (CHeCS).

Research suggests that Vietnam era veterans have a higher prevalence of hepatitis C virus (HCV) than other veterans and nonveterans. However, the reasons for this are unclear, since this research has been conducted among Department of Veterans Affairs (VA) patients and most veterans do not use the VA. The current study compares HCV risk factors between the Vietnam era veterans and nonveterans seen in 4 large non-VA systems to explain this disparity. A total of 4,636 HCV patients completed surveys in 2011-2012. Vietnam era veterans were defined as those who served in the military any time between 1964 and 1975. Bivariate tests followed by logistic regressions, and multivariable modeling were conducted to study risk factors among Vietnam era veterans and nonveterans. Since few veterans were female (~2 %), they were excluded. Among male respondents (N = 2,638), 22.5 % were classified as Vietnam era veterans. Compared to nonveterans, these patients were older (p < 0.001), more educated (p < 0.001), less often foreign born (p = 0.009), more often married (p < 0.001), less often employed, and less likely to have a history of drug abuse treatment (p < 0.001). Comparison of specific risk factor differences for HCV infection by veteran status suggested that while injection drug use approached statistical significance (nonveterans = 46.1 % vs. Vietnam era veterans = 41.4 %, p = 0.06), only reported sex with men was significant (nonveterans = 2.4 % vs. Vietnam era veterans = 0.6 %, p = 0.013). In multivariate logistic regression controlling for age, education, country of birth, marital status and study site, no HCV risk factor was associated with Vietnam era veteran status. However, veterans were more likely to report "other" exposures were the source of infection than nonveterans (p < 0.001). While Vietnam era veterans seen in non-VA facilities do not report a higher prevalence of common HCV risk factors, such as injection drug use, they are more likely to report "other" exposures, typically associated with military service, as the source of HCV infection.

Noninvasive serum fibrosis markers for screening and staging chronic hepatitis C virus patients in a large US cohort.

BACKGROUND: Liver biopsy remains critical for staging liver disease in hepatitis C virus (HCV)-infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis sought to validate APRI (aspartate aminotransferase [AST]-to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase [ALT], AST, and platelets plus patient age) to stage liver disease. METHODS: Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0-F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale. RESULTS: We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3-F4) from mild-to-moderate fibrosis (F0-F2) were 0.80 (95% confidence interval [CI], .78-.82) for APRI and 0.83 (95% CI, .81-.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher. CONCLUSIONS: In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.

Higher percent body fat in young women with lower physical activity level and greater proportion Pacific Islander ancestry.

Samoan women exhibit high rates of obesity, which can possibly be attenuated through diet and physical activity. Obesity, and body fatness in particular, is associated with increased risk for chronic diseases. Ancestry, physical activity, and dietary patterns have been associated with body composition. Using a cross-sectional design, the relative importance of proportion of Pacific Islander (PI) ancestry, level of physical activity, and macronutrients among healthy women in Honolulu, Hawai'i, ages 18 to 28 years was examined. All data were collected between January 2003 and December 2004. Percent body fat (%BF) was determined by whole body dual energy x-ray absorptiometry (DXA). Nutrient data were derived from a three-day food record. Means and standard deviations were computed for all variables of interest. Bivariate correlation analysis was used to determine correlates of %BF. Multiple regression analysis was used to determine relative contribution of variables significantly associated with %BF. Proportion of PI ancestry was significantly positively associated with %BF (P=0.0001). Physical activity level was significantly negatively associated with %BF (P=0.0006). Intervention to increase physical activity level of young Samoan women may be effective to decrease body fat and improve health. CRC-NIH grant: 0216.

Development and implementation of a food system intervention to prevent childhood obesity in rural Hawai'i.

This paper presents details the Healthy Foods Hawai'i (HFH) intervention trial, aimed to improve children's dietary behavior to prevent child obesity, by modifying the food environment with community-selected foods. Four communities were selected by ethnic composition, income level, two on O'ahu and one neighbor island. On each island one community was randomly assigned to intervention and one to control. The intervention was implemented through food stores in the intervention communities. HFH was designed to strengthen the network between local food producers, food distributors, storeowners and consumers, to increase the availability of healthier less energy dense foods for children in underserved rural communities of Hawai'i. The intervention includes phases: healthier beverages, snacks, condiments, and family meals. Moderate to high fidelity was achieved for educational materials (shelf labels, posters and educational displays). The number of educational displays varied by intervention phase and community. Posters were found in place 100% of the time. Shelf labels were found intact in the correct location. Low to moderate fidelity was achieved for distributors, with some products not stocked. In the intervention communities, 6-8 week phases focused on target foods with 40 food demonstrations. A total of 1582 food related samples were distributed. A high to moderate dose and reach of the overall intervention was achieved in delivery of the cooking demonstrations. A high to moderate dose and reach of the intervention was achieved overall; fidelity to the intervention protocol was moderate. To improve healthy local food availability in stores in rural communities in Hawai'i, agricultural producers reported needing additional support to sell and transport product to local stores, rather than to centralized distributors.

Association of maternal and intrauterine characteristics with age at menarche in a multiethnic population in Hawaii.

This study seeks to further elucidate the mother-daughter hormonal relationship and its effects on daughter's breast cancer risk through the association with early age at menarche. Four hundred and thirty-eight healthy girls, age 9-18 and of White, Asian, and/or Polynesian race/ethnicity, were recruited from an HMO on Oahu, Hawaii. Anthropometric measures were taken at a clinic visit, and family background questionnaires were completed. Cox proportional hazards regression was used to test the association of maternal and intrauterine hormone-related exposures with age at menarche. Weight and gestational age at birth and maternal pregnancy-induced nausea were not associated with age at menarche. Each year older of the mother's age at menarche was associated with a 21% reduced risk of an early age at menarche for the daughter (95% CI: 0.73-0.86). This association between mother's and daughter's menarcheal age was statistically significant for girls of Asian, White, and Mixed, Asian/White race/ethnicity, but not for girls of Mixed, part-Polynesian race/ethnicity (p (interaction) = 0.01). There was a suggestion that maternal history of breast cancer was associated with an increased risk of early age at menarche (HR = 2.18, 95% CI: 0.95-4.98); there was no association with second-degree family history. These findings support the hypothesis that maternal and intrauterine hormone-related exposures are associated with age at menarche.

Bisphosphonate Drug Holiday and Fracture Risk: A Population-Based Cohort Study.

Holidays from bisphosphonates (BPs) may help to prevent rare adverse events such as atypical femoral fractures, but may be appropriate only if risk of osteoporosis-related fractures does not increase. Our objective was to compare the incidence of osteoporosis-related fractures among women who had a BP holiday to those who continued to use BPs. This retrospective cohort study, conducted within four Kaiser Permanente integrated health system regions, included 39,502 women aged ≥45 years with ≥3 years exposure to BP. Participants with a BP holiday (≥12 months with no use) were compared to persistent (use with ≥50% adherence) and nonpersistent (use with <50% adherence) users for incident osteoporosis-related fractures. The BP holiday (n = 11,497), nonpersistent user (n = 10,882), and persistent user groups (n = 17,123) were observed for 156,657 person-years. A total of 5199 osteoporosis-related fractures (including 1515 hip fractures and 2147 vertebral fractures) were observed. Compared to the persistent use group, there was a slight difference in overall osteoporosis-related fracture risk (HR 0.92; 95% CI, 0.84 to 0.99)and no difference in hip fracture risk (HR 0.95; 95% CI, 0.83 to 1.10) for the BP holiday group. A slight reduction in risk of vertebral fracture was observed (HR 0.83; 95% CI, 0.74 to 0.95). Compared to the nonpersistent user group, the BP holiday group was at decreased risk for osteoporosis-related fractures (HR 0.71; 95% CI, 0.65 to 0.79), vertebral fractures (HR 0.68; 95% CI, 0.59 to 0.78), and hip fractures (HR 0.59; 95% CI, 0.50 to 0.70). Women who undertake a BP holiday from BP of ≥12 months duration for any reason after ≥3 years of BP use do not appear to be at greater risk of osteoporosis-related fragility fracture, hip, or vertebral fractures compared to ongoing BP users. In our cohort, BP holiday remains a viable strategy for balancing the benefits and potential harms associated with long-term BP use. © 2018 American Society for Bone and Mineral Research.

Dietary patterns of adolescent girls in Hawaii over a 2-year period.

OBJECTIVE: To describe changes in dietary patterns of adolescent girls in Hawaii from 2001 to 2003. DESIGN: Cohort study, with exams 2 years apart. SUBJECTS/SETTING: One hundred fifty-one girls of Asian, white, and mixed ethnicity who were aged 9 to 14 years at exam 1 and aged 11 to 16 years at exam 2 and lived on the island of Oahu, HI. METHODS: Three-day diet records were obtained at each exam. Mean nutrient and food group intakes and weight, height, and body mass index were determined and compared between the two exams. STATISTICAL ANALYSES: Data are summarized as means+/-standard deviation unless otherwise stated. Differences in values between groups were analyzed for significance using paired t tests and multiple regression. RESULTS: Girls at exams 1 and 2 had mean carbohydrate intakes of 233 g and 241 g, respectively, and protein intakes of 67 g and 65 g, respectively. None of the carbohydrate intakes were below the Estimated Average Requirement (EAR) at exam 1 and only one girl was below at exam 2. Three percent of girls had protein intakes that were below the EAR at exam 1 whereas 9% were below at exam 2. For iron intakes, 3% of girls were below the EAR at exam 1 and 14% of girls were below at exam 2. Girls at exams 1 and 2 had mean calcium intakes of 733 mg and 732 mg, respectively, and fiber intakes of 11.2 g and 11.4 g, respectively; lower than the Adequate Intake recommendation. The percentage of energy from macronutrients in exams 1 and 2, respectively, was in range of the Appropriate Macronutrient Distribution Range for more than 70% of girls (76% for exam 1, 79% for exam 2), but the mean percentage intake of saturated fat intake was higher than the recommended range for more than 65% of the girls at both exams 1 and 2 (69% at exam 1, 73% at exam 2). However, no significant differences were found in percent contribution of or in total intake of macronutrients between the two exams. More than half of girls (51% to 100%) did not consume the recommended number of Food Guide Pyramid Servings for any food group at either exam 1 or 2. A significant increase was found for sweetened carbonated beverage intake (from 130 g to 179 g; P<0.05) and for added sugar intake (from 16 tsp to 18 tsp; P<0.01) between exams 1 and 2, a level well above recommendations. As expected, mean body weight and mean body mass index increased significantly between exams 1 and 2 (P<0.05). CONCLUSIONS: These data suggest high dietary intakes of dietary fat and sugar, and increasing intakes of sweetened carbonated beverages and other high-sugar drinks during adolescence among girls in Hawaii.

Breastfeeding is associated with lower body mass index among children of the Commonwealth of the Northern Mariana Islands.

OBJECTIVE: To describe the prevalence of breastfeeding and overweight in the Commonwealth of the Northern Mariana Islands (CNMI), and the relationship between the two. DESIGN AND METHODS: A random cluster survey of 420 children (aged 6 months to 10 years), was conducted in the CNMI in June and July of 2005. Children were measured for weight and height and caregivers were asked about past feeding habits by trained investigators. RESULTS: Seventy-three percent of children were ever breastfed; 53% were still breastfed at 6 months, and 22% at 1 year of age. Five percent of children were found to be underweight (<5th percentile), while 15% were at risk for overweight (85th to <95th percentile) and 19% were overweight (>95th percentile), according to the Centers for Disease Control and Prevention body mass index for age reference data. Children who had been breastfed had a substantially lower body mass index than children who had not breastfed, after adjusting for age, sex, birthweight, and years of mother's education. DISCUSSION: These findings will be used to guide program development in the CNMI.

CER Hub: An informatics platform for conducting comparative effectiveness research using multi-institutional, heterogeneous, electronic clinical data.

OBJECTIVES: Comparative effectiveness research (CER) requires the capture and analysis of data from disparate sources, often from a variety of institutions with diverse electronic health record (EHR) implementations. In this paper we describe the CER Hub, a web-based informatics platform for developing and conducting research studies that combine comprehensive electronic clinical data from multiple health care organizations. METHODS: The CER Hub platform implements a data processing pipeline that employs informatics standards for data representation and web-based tools for developing study-specific data processing applications, providing standardized access to the patient-centric electronic health record (EHR) across organizations. RESULTS: The CER Hub is being used to conduct two CER studies utilizing data from six geographically distributed and demographically diverse health systems. These foundational studies address the effectiveness of medications for controlling asthma and the effectiveness of smoking cessation services delivered in primary care. DISCUSSION: The CER Hub includes four key capabilities: the ability to process and analyze both free-text and coded clinical data in the EHR; a data processing environment supported by distributed data and study governance processes; a clinical data-interchange format for facilitating standardized extraction of clinical data from EHRs; and a library of shareable clinical data processing applications. CONCLUSION: CER requires coordinated and scalable methods for extracting, aggregating, and analyzing complex, multi-institutional clinical data. By offering a range of informatics tools integrated into a framework for conducting studies using EHR data, the CER Hub provides a solution to the challenges of multi-institutional research using electronic medical record data.

Impact of implementing glycated hemoglobin testing for identification of dysglycemia in youth.

OBJECTIVES: To determine the impact of the introduction of the glycated hemoglobin (HbA1C) assay for diabetes mellitus diagnosis among children and adolescents aged 6-17 years and to describe the composition of the population of patients with, and at risk for, diabetes using fasting plasma glucose test and HbA1C assay. RESEARCH DESIGN AND METHODS: The Kaiser Permanente Hawaii (KPHI) and Kaiser Permanente Northwest (KPNW) sites identified a 2009 and a 2012 cohort of youth who were aged 6-17 years and continuously enrolled in their cohort year and for 1 year prior. We excluded youth with a type 1 or type 2 diabetes diagnosis before their cohort year. RESULTS: In both sites, fasting plasma glucose testing was significantly more common in 2009 and HbA1C testing was more common in 2012. The proportion with either test increased from 2.56% to 4.02% in KPNW and from 3.18% to 10.48% in KPHI, but the characteristics of the population did not change between 2009 and 2012. In both sites, the characteristics of youth at risk of diabetes changed substantially with a much greater proportion being female (KPNW: 39% vs 55%; KPHI: 35% vs 46%; p < 0.001 for both) and children younger than 10 (KPNW: 7% vs 32%; KPHI: 11% vs 39%; p < 0.001 for both) between 2009 and 2012. The size and composition of the population of youth identified with diabetes was not affected. CONCLUSIONS: Adoption of the HbA1C assay for diabetes diagnosis has increased glycemia testing among youth aged 6-17 years and has altered the composition of the population identified as at risk for diabetes. These findings have important ramifications for targeted screening and diabetes prevention efforts.

Hepatitis B virus infection testing and prevalence among Asian and Pacific Islanders.

OBJECTIVES: Asian and Pacific Islanders (APIs) constitute less than 6% of the US population, but account for more than half of Americans with chronic hepatitis B virus (HBV) infection. We sought to examine the effect of country of origin on HBV testing and chronic HBV infection prevalence among APIs. METHODS: We analyzed demographic and clinical data collected for adults from Kaiser Permanente Hawaii with 1 or more healthcare encounters during 2006 to 2008, 12 months or more of follow-up before 2009, and no HBV-related diagnosis within 6 months of enrollment. Persons who received a test and a positive test result for HBV surface antigen or HBV DNA were classified "tested" and with "chronic HBV infection," respectively. RESULTS: Of 92,687 eligible APIs, 53,573 (58%) had country-of-origin data available. Among those, 41,263 were US born; 28.3% were tested; and 1.8% of those tested had chronic HBV infection. Of 12,310 foreign-born APIs, 30.5% were tested and 7.4% of those tested had chronic HBV infection. Foreignborn APIs had higher odds of being tested (odds ratio [OR] = 1.15) and testing positive (OR = 4.18) compared with US-born APIs. Persons with 2 or more abnormal tests for alanine aminotransferase (ALT) levels had higher odds of getting tested (OR = 6.12) and of testing positive (OR = 1.86) compared with persons with other ALT levels. CONCLUSIONS: Less than one-third of this managed care API population (29% of 53,573) was tested, yet the prevalence of chronic HBV infection (3.2%) was 12 times higher than that of the general US population. These findings underscore the importance of adherence to HBV testing guidelines to identify persons with infection so they may be linked to care.