Quantifying cancer risk from exposures to medical imaging in the Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study: research methods and cohort profile.

PURPOSE: The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. METHODS: The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages. RESULTS: The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine. CONCLUSION: The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.

Lung Cancer Screening by Race and Ethnicity in an Integrated Health System in Hawaii.

Importance: Racial and ethnic differences in lung cancer screening (LCS) completion and follow-up may be associated with lung cancer incidence and mortality rates among high-risk populations. Aggregation of Asian American, Native Hawaiian, and Pacific Islander racial and ethnic groups may mask the true underlying disparities in screening uptake and diagnostic follow-up, creating barriers for targeted, preventive health care. Objective: To examine racial and ethnic differences in LCS completion and follow-up rates in a multiethnic population. Design, Setting, and Participants: This population-based cohort study was conducted at a health maintenance organization in Hawaii. LCS program participants were identified using electronic medical records from January 1, 2015, to December 31, 2019. Study eligibility requirements included being aged 55 to 79 years, a 30 pack-year smoking history, a current smoker or having quit within the past 15 years, at least 5 years past any lung cancer diagnosis and treatment, and cancer free. Data analysis was performed from June 2019 to October 2020. Exposure: Eligible for LCS. Main Outcomes and Measures: Screening rates were analyzed by self-reported race and ethnicity and completion of a low-dose computed tomography (LDCT) test. Diagnostic follow-up results were based on the Lung Imaging Reporting and Data System (Lung-RADS) staging system. Results: A total of 1030 eligible LCS program members had an order placed; their mean (SD) age was 65.5 (5.8) years, and 633 (61%) were men. The largest racial and ethnic groups were non-Hispanic White (381 participants [37.0%]), Native Hawaiian or part Native Hawaiian (186 participants [18.1%]), and Japanese (146 participants [14.2%]). Men and Filipino, Chinese, Japanese, and non-Hispanic White individuals had a higher proportion of screen orders for LDCT compared with women and individuals of the other racial and ethnic groups. The overall LCS completion rate was 81% (838 participants). There was a 14% to 15% screening completion rate gap among groups. Asian individuals had the highest screening completion rate (266 participants [86%]) followed by Native Hawaiian (149 participants [80%]) and non-Hispanic White individuals (305 participants [80%]), Pacific Islander (50 participants [79%]) individuals, and individuals of other racial and ethnic groups (68 participants [77%]). Within Asian subgroups, Korean (31 participants [94%]) and Japanese (129 participants [88%]) individuals had the highest completion rates followed by Chinese individuals (28 participants [82%]) and Filipino individuals (78 participants [79%]). Of the 54 participants with Lung-RADS stage 3 disease, 93% (50 participants) completed a 6-month surveillance LDCT test; of 37 individuals with Lung-RADS stage 4 disease, 35 (97%) were followed-up for additional procedures. Conclusions and Relevance: This cohort study found racial and ethnic disparities in LCS completion rates after disaggregation of Native Hawaiian, Pacific Islander, and Asian individuals and their subgroups. These findings suggest that future research is needed to understand factors that may be associated with LCS completion and follow-up behaviors among these racial and ethnic groups.

Prevalence of diabetes and glucose intolerance in an ethnically diverse rural community of Hawaii.

BACKGROUND: We report the prevalence of diabetes in a rural, multiethnic community in Hawaii, of predominantly Asian and Native Hawaiian ancestry, by using 1997 World Health Organization diagnostic criteria applied to a two-hour oral glucose tolerance test. METHODS: This cross-sectional survey included 1452 men and nonpregnant women who were >18 years of age. Blood was drawn in the fasting and postchallenge states. Individuals under pharmacologic treatment for diabetes were excluded. Information obtained included demographics, medical history, dietary intake, physical activity, and anthropometric measurements. RESULTS: Prevalence of diabetes was approximately three-fold higher among Asian and Native Hawaiian ancestry groups than among Caucasians, even after adjusting for other risk factors. Furthermore, diabetes prevalence was similar among all non-Caucasian ethnic groups despite significant differences in body mass indices. CONCLUSIONS: These findings indicate that earlier reports of high prevalence of diagnosed diabetes among Asians and Hawaiian ethnic groups were not due to detection bias, since our study revealed similar prevalence of previously unrecognized diabetes. Furthermore, similar prevalence among these groups was observed despite significant differences in body mass indices, diet, and physical activity. This apparent paradox may reflect limitations in the measurement of these risk factors; differences in the impact of these risk factors on diabetes risk in different ethnic groups; or ethnic differences in lifestyle, biochemical, or genetic factors that were not examined in this study.

Association between angiotensin-converting enzyme gene polymorphisms and QT duration in a multiethnic population in Hawaii.

OBJECTIVES: Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii. METHODS: Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms. RESULTS: The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001). CONCLUSIONS: The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.

Metabolic syndrome in a multiethnic population in rural Hawaii.

OBJECTIVE: The National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria for metabolic syndrome (MS) provide a standard for comparing various populations. Using these criteria, the Third National Health and Nutrition Examination Survey reported an overall US prevalence of 21.8%. With these same criteria, we estimated the prevalence of MS among a multiethnic population in rural Hawaii. DESIGN: These data are from a cross-sectional survey from 1997-2000. SETTING: The survey was conducted in the rural community of North Kohala. PARTICIPANTS: More than 1,450 adult residents from five ethnic categories were included: Caucasian, Japanese, Filipino, Hawaiian/part-Hawaiian, Other/mixed non-Hawaiian. Ethnic ancestry was determined by self-report. Ethnic differences were compared by using logistic regression. MAIN OUTCOMES: Blood pressure, height, weight, and waist circumference, fasting and two-hour post-oral glucose challenge plasma was obtained for lipid and glucose determinations. RESULTS: Overall prevalence was 33.4%. Prevalence was significantly higher among all ethnic groups when compared to Caucasians. Despite significant differences in the prevalence of overweight and abdominal obesity, the prevalence of MS was similar in all non-Caucasian ethnic groups. Filipinos had the highest adjusted odds for prevalent MS (prevalence OR=4.2; 95% CI=2.4-7.3). CONCLUSION: Metabolic syndrome (MS) prevalence was high in Asian ethnic groups previously reported to have low cardiovascular disease (CVD) mortality. These findings suggest either a differential effect of CVD risk factors on mortality among some ethnic groups, or more likely, that future mortality rates will increase among those ethnic groups that currently enjoy low mortality rates.

Prevalence and risk factors for prolonged QTc in a multiethnic cohort in rural Hawaii.

BACKGROUND: Few studies have examined the biochemical risk factors for prolonged QTc, a predictor of mortality in numerous studies. We report on the prevalence and risk factors for prolonged QTc in a multiethnic population in rural Hawaii. METHODS: Electrocardiograms were collected from 1415 participants in a cross-sectional survey. The QT interval lengths were corrected for heart rate using Bazett's formula. Linear and logistic regression models were used to examine associations between various cardiovascular risk factors with QTc. RESULTS: Among the CVD risk factors examined, only age, gender, 2-h glucose, and systolic blood pressure (SBP) were independently associated with QTc interval length. Significant ethnic differences in prevalence were also observed, which persisted after controlling for other risk factors. CONCLUSIONS: Significant associations between prolonged QTc and ethnic ancestry, but not cholesterol or triglyceride levels, suggest that genetic factors may play a more important role in determining QTc interval length than conventional biochemical and metabolic CVD risk factors.

Early weaning among Japanese women in Hawaii.

This study examined factors associated with early weaning among Japanese women in comparison with Caucasian women in Hawaii. A mailed survey was sent to all women who delivered an infant in Hawaii between January 1st 1989 and March 31st 1989. Only Japanese (N=228) and Caucasian women (N=439) were included in this study. All Japanese breast-feeding women in the study introduced formula at some point in time. Cox multivariate regression analysis was conducted in two separate models of Japanese and Caucasian women, respectively. Higher maternal age and working part-time among Japanese women, and multiparity, college education, rural island and long-term Hawaii residence among Caucasian women were protective against early weaning. Introduction of formula was strongly associated with early weaning for both groups, the association being stronger for Japanese women. The early practice of partial breast-feeding may play an important role for early weaning among Japanese women in Hawaii.

Healthy people in Hawaii?: an overview of ethnic health disparities in Hawaii for the Healthy People 2010 initiative targeted health concerns.

Significant health disparities exist between ethnic groups in the United States. The authors reviewed literature examining the epidemiology of health disparities in Hawaii's multiethnic population. One of the primary goals of the Healthy People 2010 initiative is to eliminate health disparities, specifically cancer, cardiovascular disease, diabetes, infant mortality, child and adult immunizations and HIV/AIDS. However, the research on ethnic health disparities is fragmented, especially in Asian/Pacific Islanders. Unclear definitions of ethnicity (i.e., self-report, mixed ethnicity, etc) and aggregated study populations (i.e., combining multiple ethnic groups into one category) obscure the true health status of ethnic minorities in Hawaii. This paper presents an overview of the state of the literature on Hawaii ethnic health disparities.

US birth weight/gestational age-specific neonatal mortality: 1995-1997 rates for whites, hispanics, and blacks.

OBJECTIVE: In recent years, gains in neonatal survival have been most evident among very low birth weight, preterm, and low birth weight (LBW) infants. Most of the improvement in neonatal survival since the early 1980s seems to be the consequence of decreasing birth weight-specific mortality rates, which occurred during a period of increasing preterm and LBW rates. Although the decline in neonatal mortality has been widely publicized in the United States, research suggests that clinicians may still underestimate the chances of survival of an infant who is born too early or too small and may overestimate the eventuality of serious disability. So that clinicians may have current and needed ethnic- and race-specific estimates of the "chances" of early survival for newborn infants, we examined birth weight/gestational age-specific neonatal mortality rates for the 3 largest ethnic/racial groups in the United States: non-Hispanic whites, Hispanics, and non-Hispanic blacks. Marked racial variation in birth weight and gestational age-specific mortality has long been recognized, and growing concerns have been raised about ongoing and increasing racial disparities in pregnancy outcomes. Our purpose for this investigation was to provide an up-to-date national reference for birth weight/gestational age-specific neonatal mortality rates for use by clinicians in care decision making and discussions with parents. METHODS: The National Center for Health Statistics linked live birth-infant death cohort files for 1995-1997 were used for this study. Singleton live births to US resident mothers with a reported maternal ethnicity/race of non-Hispanic white, non-Hispanic black, or Hispanic (n = 10 610 715) were selected for analysis. Birth weight/gestational age-specific neonatal mortality rates were calculated using 250 g/2-week intervals for each ethnic/racial group. RESULTS: The overall neonatal mortality rates for whites, Hispanics, and blacks were 3.24, 3.45, and 8.16 neonatal deaths per 1000 live births, and the proportion of births <28 weeks was 0.35%, 0.45%, and 1.39%, respectively. Newborns who weighed <1500 g comprised <2.5% of all births in each racial/ethnic group but accounted for >50% of neonatal deaths. For whites, Hispanics, and blacks, >50% of newborns 24 to 25 weeks of gestational age survived. For most combinations of birth weights <3500 g and gestational ages of <37 weeks, the neonatal mortality rate was lowest among blacks, compared with whites or Hispanics. At these same gestational age/birth weight combinations, Hispanics have slightly lower mortality rates than whites. For combinations of birth weights >3500 g and gestational ages of 37 to 41 weeks, Hispanics had the lowest neonatal mortality rate. In these birth weight/gestational age combinations, where approximately two thirds of births occur, blacks had the highest neonatal mortality rate. CONCLUSIONS: Compared with earlier reports, these data suggest that a substantial improvement in birth weight/gestational age-specific neonatal mortality has occurred in the United States. Regardless of ethnicity/race, the risk of a neonatal death does not exceed 50% (the suggested definition for the limit of viability), except for birth weights below 500 g and gestational ages <24 weeks. Notwithstanding, ethnic/racial variations in neonatal mortality rates continue to persist, both in overall rates and within birth weight/gestational age categories. Blacks continue to have higher proportions for preterm and LBW births, compared with either whites or Hispanics. At the same time, blacks experience lower risks of neonatal mortality for preterm and LBW infants, while having higher risks of mortality among term, postterm, normal birth weight, and macrosomic births.

Ginkgo biloba for the prevention of severe acute mountain sickness (AMS) starting one day before rapid ascent.

Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness (AMS) during gradual ascent. This trial was designed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent. In this double-blind, randomized, placebo-controlled trial, 26 participants residing at sea level received ginkgo (60 mg TID) or placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were transported from sea level to the summit (4205 m) over 3 hours, including 1 hour at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score (LLSR) >/= 3 with headache. Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21-53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on placebo developed severe AMS and required descent for their safety (p = 0.021); all recovered without sequelae. Median LLSR at 4205 m was significantly lower for ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26 (81%) subjects developed AMS overall. This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 m.

Native Hawaiian Birth Weight and Infant Mortality: Is Birth in Hawai'i Protective?

PURPOSE OF THE PAPER: This study provides baseline information on the characteristics of Native Hawaiian mothers and the health status of their infants, comparing residents of Hawaii with those of the continental U.S. The impact of Hawaii residence on low birth weight and infant mortality among Native Hawaiians is assessed. SUMMARY OF METHODS UTILIZED: Data from the National Center for Health Statistics 1983­1987 Linked U.S. Live Birth and Infant Death file were used to examine parental characteristics, prenatal care use and infant outcomes using chi­square and logistic regression procedures. PRINCIPAL FINDINGS: Despite a higher sociodemographic risk profile among Hawaii resident mothers, preterm birth, low and very low birth weight percentages were similar. Continental infants had significantly highter percentages of very pre­term birth and macrosomia. Mortality rates in both the neonatal and post­neonatal periods, and for SIDS and perinatal causes were elevated among continental infants. Hawaii residence had a borderline protective effect on infant mortality, wehn sociodemographic and prenatal care differences were controlled. CONCLUSIONS: This study suggests a possibly protective effect of Hawaii residence on the health of Native Hawaiian infants during the period of following employer­mandated health insurance coverage but before the initiation of "gap­group" coverage and the Native Hawaiian Health Care Systems in Hawaii. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS. This is the first report documenting the sociodemographic and health status of the growing number of Native Hawaiian mothers and their infants residing outside of Hawaii. Expanded health insurance coverage and culturally appropriate and accessible health care may contribute to improved infant health status in Hawaii. Their absence, along with possible barriers of sociocultural isolation, may account for the poorer than expected outcomes of continental infants and predict a widening gap between them and their counterparts in Hawaii. A follow­up study of the health status of Native Hawaiian mothers and infants, and their access to appropriate care in Hawaii and thei continental U.S. is recommended.

Pregnancy outcomes among Whites and Filipinos: A paradoxical birth weight-neonatal mortality relationship.

Evidence from the Philippines suggests that, compared to Whites, infants born to Filipino women are more likely to be low birth weight. A paucity of information is available regarding birth outcomes of U.S.-born Filipinos. Using 1979-1987 Hawaii vital record data on single live births to resident mothers, this study compares the maternal characteristics and pregnancy outcomes of White and Filipino mothers, Filipino mothers were significantly more likely to be <18 years of age and single, and have lower educational attainment and less adequate utilization of prenatal care. Significantly higher percentages of very preterm, preterm, very low birth weight, low birth weight, and small for gestational age infants were found for Filipinos. The birth weight-specific neonatal mortality rates for Filipinos compared favorably to Whites except at the high end of the birth weight distribution. After taking into account maternal sociodemographic risk and prenatal care factors in a logistic regression, a significant ethnic difference in low birth weight persisted but was not found for neonatal mortality. These data may suggest that similar neonatal mortality rates among ethnic groups may be possible in the face of persistent birth weight distribution differences and add to the growing evidence that a single standard of low birth weight may be inappropriate as an universal indicator of health status risk in a multi-ethnic population. © 1993 Wiley-Liss, Inc.