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Hemorrhagic disease (HD) of deer is caused by epizootic hemorrhagic disease virus (EHDV) or bluetongue virus (BTV) and is considered one of the most important viral diseases of white-tailed deer (Odocoileus virginianus). Despite evidence of changing patterns of HD in the northeastern and upper midwestern US, the historical and current patterns of HD in the Great Plains remain poorly described. We used results from an annual survey documenting HD mortality to characterize historic and current patterns of HD in the northern and central Great Plains (North Dakota, South Dakota, Nebraska, Kansas, and Oklahoma), US, between 1982 and 2020. Further, we assessed temporal change using linear regression to determine change in annual reporting intensity (percentage of counties in a state with reported HD) and change in reporting frequency (the number of years a county or state reported HD) during each decade between 1982 and 2020. Across the 38-yr study period, HD reports expanded northeast across latitude and longitude. Intensity of HD reports significantly increased during this period for three (North Dakota, South Dakota, Kansas) of five states examined. Frequency of reports also increased for all five states. Such changes in northern latitudes might lead to increased deer mortality in regions where HD epizootics have been historically less frequent. Understanding how patterns of HD are changing on the landscape is important when considering future deer management in the face of other mortality factors., (© Wildlife Disease Association 2024.)

Background: The aim of this study is to compare impact of COVID-19 on trauma volume and characteristics on a set of trauma centers with a rural catchment area. The COVID-19 pandemic has affected different parts of the country quite differently, both in case volume and in local responses. State-wide responses have varied considerably, including variations in local mask mandates, school closures, and social distancing measures., Methods: This was a retrospective trauma registry review of patients who were admitted to three of the tertiary care trauma centers in North and South Dakota between 2014 through 2022., Results: In the analysis of 36,397 patients, we found a significant increase in trauma patient volume during the COVID-19 pandemic, with an increased percentage of patients presenting with a mechanism of injury secondary to abuse or assault. This increase in patient volume continued to rise during 2021 and 2022., Conclusions: Our study demonstrates how the COVID-19 pandemic impacted trauma center admissions in the rural and frontier Midwest differently from more urban areas, and the importance of including a variety of settings in trauma research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study investigates the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission potential in North Dakota, South Dakota, Montana, Wyoming, and Idaho from March 2020 through January 2021., Methods: Time-varying reproduction numbers, R t , of a 7-d-sliding-window and of non-overlapping-windows between policy changes were estimated using the instantaneous reproduction number method. Linear regression was performed to evaluate if per-capita cumulative case-count varied across counties with different population size or density., Results: The median 7-d-sliding-window R t was reduced by 14.71% (95% credible interval, CrI, [14.41%, 14.99%]) in North Dakota following a mask mandate; Idaho saw a 1.93% (95% CrI [1.87%, 1.99%]) reduction and Montana saw a 9.63% (95% CrI [9.26%, 9.98%]) reduction following the tightening of restrictions. High-population and high-density counties had higher per-capita cumulative case-count in North Dakota on June 30, August 31, October 31, and December 31, 2020. In Idaho, North Dakota, South Dakota, and Wyoming, there were positive correlations between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables.R t was reduced by 14.71% (95% credible interval, CrI, [14.41%, 14.99%]) in North Dakota following a mask mandate; Idaho saw a 1.93% (95% CrI [1.87%, 1.99%]) reduction and Montana saw a 9.63% (95% CrI [9.26%, 9.98%]) reduction following the tightening of restrictions. High-population and high-density counties had higher per-capita cumulative case-count in North Dakota on June 30, August 31, October 31, and December 31, 2020. In Idaho, North Dakota, South Dakota, and Wyoming, there were positive correlations between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables., Conclusions: R t decreased after mask mandate during the region's case-count spike suggested reduction in SARS-CoV-2 transmission.

Rationale: Prior research has found adverse childhood experiences (ACEs) to be a risk factor for disability in adulthood. Moreover, accumulating evidence highlights that both ACEs and disability during pregnancy are a risk factor for both maternal and infant wellbeing. Yet, no previous work has assessed whether ACEs increase the risk of maternal disability., Objective: The current study assesses the link between maternal ACE exposure and disability., Methods: Data are from the North Dakota and South Dakota Pregnancy Risk Assessment Monitoring System (PRAMS), 2019 (N = 1775). Logistic regression was used to assess the relationship between accumulating ACEs and maternal disability., Results: Mothers with exposure to a greater number of ACE-notably, 4 or more ACEs- had elevated rates of several disabilities including difficulty communicating, difficulty remembering, difficulty seeing, and difficulty walking., Conclusions: Understanding the long-term health repercussions of ACEs for pregnant women and mothers is important to help inform the design and implementation of health care interventions. This study can be used to better understand the prevalence of disabilities among mothers and corroborate early life experiences as an important risk factor for disability., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Emerging research suggests that adverse childhood experiences (ACEs) may be a risk factor for prenatal marijuana use. This study is the first to use a representative sample from state surveillance systems to assess the connection between accumulating ACEs and marijuana use during pregnancy., Methods: Data are from the North Dakota and South Dakota Pregnancy Risk Assessment Monitoring System (PRAMS) from years 2017-2019 (N = 5399). The bivariate association between number of ACEs and marijuana use during pregnancy is assessed using a chi-square test. The multivariable association is assessed using linear probability modeling., Results: Only 0.9% of women with zero ACEs reported marijuana use during pregnancy, compared to 11.7% of women with four or more ACEs. Findings from linear probability models showed that mothers reporting two ACEs (b =0.023, 95% CI =0.003,.043), three ACEs (b =0.042, 95% CI =0.014,.069), and four or more ACEs (b =0.053, 95% CI =0.035,.071) are more likely to report marijuana use during pregnancy relative to those with zero ACEs, net of demographic and socioeconomic control variables., Conclusions: Accumulating maternal ACEs -especially four or more- is associated with increased likelihood of using marijuana during pregnancy. These findings demonstrate the early life trauma is a key social determinant of health over the life course and highlights how ACEs can contribute to intergenerational harm via the worsening of health behaviors during pregnancy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Importance: Prenatal smoking is a known modifiable risk factor for stillbirth; however, the contribution of prenatal drinking or the combination of smoking and drinking is uncertain., Objective: To examine whether prenatal exposure to alcohol and tobacco cigarettes is associated with the risk of stillbirth., Design, Setting, and Participants: The Safe Passage Study was a longitudinal, prospective cohort study with data collection conducted between August 1, 2007, and January 31, 2015. Pregnant women from Cape Town, South Africa, and the Northern Plains region of the US were recruited and followed up throughout pregnancy. Data analysis was performed from November 1, 2018, to November 20, 2020., Exposure: Maternal consumption of alcohol and tobacco cigarettes in the prenatal period., Main Outcomes and Measures: The main outcomes were stillbirth, defined as fetal death at 20 or more weeks' gestation, and late stillbirth, defined as fetal death at 28 or more weeks' gestation. Self-reported alcohol and tobacco cigarette consumption was captured at the recruitment interview and up to 3 scheduled visits during pregnancy. Participants were followed up during pregnancy to obtain delivery outcome., Results: Of 11663 pregnancies (mean [SD] gestational age at enrollment, 18.6 [6.6] weeks) in 8506 women for whom the pregnancy outcome was known by 20 weeks' gestation or later and who did not terminate their pregnancies, there were 145 stillbirths (12.4 per 1000 pregnancies) and 82 late stillbirths (7.1 per 1000 pregnancies). A total of 59% of pregnancies were in women from South Africa, 59% were in multiracial women, 23% were in White women, 17% were in American Indian women, and 0.9% were in women of other races. A total of 8% were older than 35 years. In 51% of pregnancies, women reported no alcohol or tobacco cigarette exposure (risk of stillbirth, 4 per 1000 pregnancies). After the first trimester, 18% drank and smoked (risk of stillbirth, 15 per 1000 births), 9% drank only (risk of stillbirth, 10 per 1000 pregnancies), and 22% smoked only (risk of stillbirth, 8 per 1000 pregnancies). Compared with the reference group (pregnancies not prenatally exposed or without any exposure after the first trimester), the adjusted relative risk of late stillbirth was 2.78 (98.3% CI, 1.12-6.67) for pregnancies prenatally exposed to drinking and smoking, 2.22 (98.3% CI, 0.78-6.18) for pregnancies prenatally exposed to drinking only after the first trimester, and 1.60 (98.3% CI, 0.64-3.98) for pregnancies prenatally exposed to smoking only after the first trimester. The adjusted relative risk for all stillbirths was 1.75 (98.3% CI, 0.96-3.18) for dual exposure, 1.26 (98.3% CI, 0.58-2.74) for drinking only, and 1.27 (98.3% CI, 0.69-2.35) for smoking only compared with the reference group., Conclusions and Relevance: These results suggest that combined drinking and smoking after the first trimester of pregnancy, compared with no exposure or quitting before the end of the first trimester, may be associated with a significantly increased risk of late stillbirth.

The majority of available US-published reports present populations with community spread in urban areas. The objective of this report is to describe a rural healthcare system's utilisation of therapeutic options available to treat Coronavirus Disease 2019 (COVID-19) and subsequent patient outcomes. A total of 150 patients were treated for COVID-19 at three hospitals in the Dakotas from 21 March 2020 to 30 April 2020. The most common pharmacological treatment regimens administered were zinc, hydroxychloroquine plus azithromycin and convalescent plasma. Adjunctive treatments included therapeutic anticoagulation, tocilizumab and corticosteroids. As of 1 June 2020, 127 patients have survived to hospital discharge, 12 patients remain hospitalised and 11 patients have expired. The efficacy of hydroxychloroquine and azithromycin use has yet to be determined but was not without risks of corrected QT interval prolongation and arrhythmias in our cohort. We did not appreciate any adverse effects that appeared related to tocilizumab or convalescent plasma administration in those patient subsets. These findings may provide insight into disease severity and treatment options in the rural setting with limited resources to participate in clinical trials and encourage larger comparative studies evaluating treatment efficacy.

Introduction: Prenatal alcohol exposure is associated with adverse pregnancy outcomes such as fetal alcohol spectrum disorders. The study characterizes the pattern and risk factors of alcohol use during pregnancy for American Indian and Caucasian mothers in the Northern Plains., Methods: A general population of pregnant women was recruited from 5 sites, including 2,753 Caucasians and 2,124 American Indians (2006-2017). Alcohol consumption was based on self-report using a modified Timeline Followback interview, administered 3-4 times during pregnancy and 1 month postpartum. Risk for prenatal drinking was calculated using logistic regression models after controlling for demographics, reproductive history, prenatal care, mental health, and SES. The analysis was conducted in 2019., Results: More Caucasian mothers consumed alcoholic beverages during pregnancy than American Indians (63% vs 52%), whereas more American Indian mothers were binge drinkers than Caucasians (41% vs 28%). American Indian mothers had a lower risk of drinking in the second and third trimesters and postpartum, but a higher risk of binge drinking in the first trimester compared with Caucasians. Frequent relocation increased the risk of prenatal alcohol use among American Indian mothers, whereas age, marriage, income, parity, and fertility treatment affected the risk of prenatal drinking among Caucasian mothers., Conclusions: Alcohol use was more prevalent among Caucasian mothers. Among those who consumed alcohol during pregnancy, American Indian mothers consumed larger quantities. Change of residence was found to be the sole risk factor for prenatal drinking among American Indian mothers, whereas different and multiple risk factors were found for Caucasian mothers., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Patients residing in agricultural communities have a high risk of developing chronic kidney disease. In the Great Plains, geo-environmental risk factors (eg, variable climate, temperature, air quality, water quality, and drought) combine with agro-environmental risk factors (eg, exposure to fertilizers, soil conditioners, herbicides, fungicides, and pesticides) to increase risk for toxic nephropathy. However, research defining the specific influence of agricultural chemicals on the progression of kidney disease in rural communities has been somewhat limited. By linking retrospective clinical data within electronic medical records to environmental data from sources like US Environmental Protection Agency, analytical models are beginning to provide insight into the impact of agricultural practices on the rate of progression for kidney disease in rural communities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Reports of children with non-type b Haemophilus influenzae infection in the United States in recent years have been limited. Here, we report the spectrum and severity of disease associated with invasive non-type b H influenzae infection in 17 patients at 2 tertiary-care children's hospitals over a 2-year period. Meningitis was the most common diagnosis. The majority of the patients had neurologic sequelae, and 1 patient died. The high proportions of hospitalization, intensive care utilization, and neurologic complications reveal that non-type b H influenzae infection was associated with significant morbidity in this pediatric population., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: We investigated incidence and staging patterns of prostate, female breast, lung, and colorectal cancer among American Indians/Alaska Natives (AI/ANs) and non-Hispanic Whites (NHWs) in the Northern Plains., Methods: Cancer registry data (2002-2009) from Nebraska, North Dakota, and South Dakota were analyzed. Incidence rates were calculated and multivariate logistic regression analyses identified factors associated with unstaged versus staged and late-stage cancer cases versus early., Results: The incidence rate was higher among AI/ANs than NHWs for lung cancer (92.2 vs. 60.6 per 100,000). Compared with NHWs, AI/ANs were 2.0 times more likely to receive an unstaged diagnosis and 1.2 times more likely to receive a late-stage diagnosis. AI/ANs were significantly more likely than NHWs to receive an unstaged diagnosis., Discussion: Increased efforts are needed to reduce unstaged and late-stage diagnoses among Northern Plains AIs. Efforts to promote early detection of cancer should target younger AI/ANs.

Background: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults., Methods: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45-74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m, kidney transplant or dialysis., Results: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4)., Conclusions: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development.

Background: Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. Prospective studies on carcinogenic effects at low-moderate arsenic levels are lacking., Methods: We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians, 45 to 74 years of age, from Arizona, Oklahoma, and North/South Dakota who participated in the Strong Heart Study from 1989 to 1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, and 40 lymphatic/hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate, and kidney cancers., Results: Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8-15.6) μg/g creatinine. The adjusted HRs [95% confidence interval (CI)] comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92-1.41) for overall cancer, 1.56 (1.02-2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28-8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09-5.58) for pancreatic cancer, and 0.46 (0.22-0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast., Conclusions: Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate, and pancreas., Impact: These findings support the role of low-moderate arsenic exposure in development of lung, prostate, and pancreas cancer and can inform arsenic risk assessment., (©2013 AACR.)

Background: Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort., Methods: We conducted a prospective cohort study of 3348 American Indian adults 45-74 years of age from Arizona, Oklahoma, and North and South Dakota, who participated in the Strong Heart Study in 1989-1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008., Results: The geometric mean cadmium level in the study population was 0.94 μg/g (95% confidence interval [CI] = 0.92-0.96). We identified 1084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (HRs) (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% CI = 1.21-1.70) and 1.34 for coronary heart disease mortality (1.10-1.63). The corresponding HRs for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11-1.38), 1.22 (1.08-1.38), 1.75 (1.17-2.59), and 1.39 (1.01-1.94), respectively. The associations were similar in most study subgroups, including never-smokers., Conclusions: Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor.

Objective: To determine the prevalence of selected virulence genes and the antimicrobial susceptibility of multidrug-resistant (MDR) Escherichia coli isolated from diarrheic neonatal calves., Sample: 97 E coli isolates from diarrheic neonatal calves., Procedures: E coli isolates were tested via PCR assay for 6 virulence genes and susceptibility to 17 drugs belonging to 9 classes. A 2-sample test of proportions was used to make comparisons between proportions of virulent and avirulent MDR isolates., Results: 23 of 97 (23.7%) isolates were virulent, and 74 (76.3%) were avirulent. Of the 23 virulent isolates, 15 (65.2%) were positive for K99, 14 (60.9%) for F41, 12 (52.2%) for STa, 9 (39.1%) for Stx1, 6 (26.1%) for intimin, and 0 (0%) for Stx2. Twenty of 23 (87.0%) virulent isolates expressed ≥ 2 virulence genes, and 3 of 23 (13.0%) were positive for 1 virulence factor. Eight of 23 (34.8%) virulent isolates expressed STa, K99, and F41, whereas 1 of 23 (4.4%) was positive for STa, F41, intimin, and Stx1. The second most frequent gene pattern was Stx1 and intimin. Twenty of 23 (87.0%) virulent isolates were MDR; the highest prevalence of resistance was recorded for the macrolide-lincosides, followed by the tetracyclines and penicillins. Also, 17 of 23 (74.0%) virulent isolates were resistant to sulfadimethoxine, and 10 of 23 (43.5%) were resistant to trimethoprim-sulfamethoxazole. Additionally, 60 of 74 (81.0%) avirulent isolates were MDR., Conclusions and Clinical Relevance: The prevalence of multidrug resistance was comparable for virulent and avirulent E coli isolated from diarrheic neonatal calves. Cephalosporins and aminoglycosides had reasonable susceptibility.

Objectives: We examined behavioral trends associated with cancer risk and cancer screening use from 1997 through 2006 among American Indians/Alaska Natives (AI/ANs) in the Northern Plains region (North Dakota, South Dakota, Nebraska, and Iowa) of the United States. We also examined disparities between that population and non-Hispanic white (NHW) people in the Northern Plains and AI/ANs in other regions., Methods: We analyzed Behavioral Risk Factor Surveillance System data from the Centers for Disease Control and Prevention for 1997-2000 and 2003-2006. We used age-adjusted Wald Chi-square tests to test the difference between these two periods for AI/ANs and the difference between AI/ANs and NHW people during 2003-2006., Results: There was no statistically significant improvement among AI/ANs in the Northern Plains region for behaviors associated with cancer risk or cancer screening use, and there was a significant increase in the obesity rate. The prevalence of binge drinking, obesity, and smoking among AI/ANs in the Northern Plains was significantly higher than among NHW people in the same region and among AI/AN populations in other regions. Although the percentage of cancer screening use was similar for all three groups, the use of sigmoidoscopy/colonoscopy was significantly lower among the Northern Plains AI/ANs than among NHW people., Conclusion: These results indicate a need for increased efforts to close the gaps in cancer health disparities between AI/ANs and the general population. Future efforts should focus not only on individual-level changes, but also on system-level changes to build infrastructure to promote healthy living and to increase access to cancer screening.

Background: The association between prediabetes as currently defined and incident diabetes in populations with widespread obesity, insulin resistance syndrome, and diabetes is not well defined. In this article, diabetes risk factors and incidence rates in American Indians (AI) with prediabetes are examined., Methods: A total of 1677 AI who were nondiabetic at baseline was examined during a median 7.8-year follow-up as part of the Strong Heart Study (SHS). Risk factors for incident diabetes were measured. Prediabetes was defined according to American Diabetes Association 2003 criteria as having impaired glucose tolerance (IGT) (2-h plasma glucose [2-h PG] >or= 140 mg/dL but < 200 mg/dL) and/or impaired fasting glucose (IFG) (fasting plasma glucose [FPG] >or= 100 mg/dL but < 126 mg/dL)., Results: Prediabetes was identified by FPG alone in 87.5%. Diabetes incidence in those with baseline prediabetes was 66.1/1000 person-years, with a hazard ratio (HR) of 2.35 (95% conference interval: 1.84-3.01), compared with participants with normal glucose tolerance (NGT) at baseline. Elevated A(1c), 2-h PG, and fasting insulin (FI); albuminuria; and obesity were significantly associated with conversion from prediabetes to diabetes. Younger age, elevated FI (or body mass index [BMI] in models without FI), and less physical activity were significantly associated with conversion from NGT., Conclusions: Prediabetes is an independent predictor of conversion to type 2 diabetes in AI, and most can be identified through a fasting glucose measure. Measures of obesity, A(1c), FPG, 2-h PG, FI, albuminuria, and insulin resistance (IR) help predict this conversion. Obesity is a modifiable risk factor. Strategies to reduce obesity should be emphasized in individuals with prediabetes., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age x sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean +/- SD serum uric acid for all individuals was 5.14 +/- 1.5 mg/dl. Serum uric acid was found to be significantly heritable (0.46 +/- 0.03 in all centers, and 0.39 +/- 0.07, 0.51 +/- 0.05, 0.44 +/- 0.06 in Arizona, Dakotas and Oklahoma, respectively). Multipoint linkage analysis showed significant evidence of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm of odds score (LOD) = 3.02] and in the combined sample (LOD = 3.56) and on chromosome 1 (LOD = 3.51) in the combined sample. A strong positional candidate gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12) that encodes a major uric acid transporter URAT1. These results show a significant genetic influence and a possible role for one or more genes on chromosomes 1 and 11 on the variation in serum uric acid in American Indian populations.

Background: The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.8 fold for 1 g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations., Methods: The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program., Results: Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28 cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (STAT3), were identified within 2 and 8 Mb of this 1 LOD drop interval respectively. A LOD score of 1.82 on chromosome 17 between 68 and 93 cM is supported by reports from two other populations with LOD scores of 1.4 and 1.95., Conclusion: In a minority population with a high prevalence of cardiovascular disease, strong evidence for a novel genetic determinant of fibrinogen levels is found on chromosome 7 at 28 cM. Four other loci, some of which have been suggested by previous studies, were also identified.

Objectives: Studies conducted in the 1980s, when there was limited chlamydia screening, showed high positivity, 23%-30%, among American Indian women. In the 1990 s, chlamydia screening and treatment programs were implemented in a variety of settings serving American Indian women including Indian Health Service (IHS) clinics. Yet, a 2000-2001 national survey documented a chlamydia prevalence of 13.3% among young American Indian women, five times higher than the prevalence among whites. The purpose of this analysis was to determine the chlamydia positivity and risk factors for chlamydia among women screened in Indian Health Service (IHS) clinics participating in the National Infertility Prevention Program in 2003., Methods: Data were analyzed from 11,485 chlamydia tests performed among women universally screened in 23 IHS clinics in three states (Montana, North Dakota, South Dakota). Sexual risk history and clinical data were collected in the Montana IHS clinics and used to assess risk factors for chlamydial infection in a multivariate logistic regression model., Results: Chlamydia positivity was highest among 15-19 year old women screened in IHS clinics (state range: 15.3%-18.6%). Positivity decreased with age but remained high even among women aged 30-34 years. Young age and having had multiple or new sex partners in the last 90 days were associated with an increased risk of chlamydia; however, chlamydia positivity was greater than 6.7% for women with no known risk factors., Conclusions: A greater emphasis on chlamydia screening and treatment should be a component of any program whose goal is to improve the reproductive health of American Indian women.

Background: Despite growing recognition that asthma is an important cause of morbidity among American Indians, there has been no systematic study of this disease in older adults who are likely to be at high risk of complications related to asthma. Characterization of the impact of asthma among American Indian adults is necessary in order to design appropriate clinical and preventive measures., Methods: A sample of participants in the third examination of the Strong Heart Study, a multicenter, population-based, prospective study of cardiovascular disease in American Indians, completed a standardized respiratory questionnaire, performed spirometry, and underwent allergen skin testing. Participants were > or = 50 years old., Results: Of 3,197 participants in the third examination, 6.3% had physician-diagnosed asthma and 4.3% had probable asthma. Women had a higher prevalence of physician-diagnosed asthma than men (8.2% vs 3.2%). Of the 435 participants reported in the asthma substudy, morbidity related to asthma was high: among those with physician-diagnosed asthma: 97% reported trouble breathing and 52% had severe persistent disease. The mean FEV(1) in those with physician-diagnosed asthma was 61.3% of predicted, and 67.2% reported a history of emergency department visits and/or hospitalizations in the last year, yet only 3% were receiving regular inhaled corticosteroids., Conclusions: The prevalence of asthma among older American Indians residing in three separate geographic areas of the United States was similar to rates in other ethnic groups. Asthma was associated with low lung function, significant morbidity and health-care utilization, yet medications for pulmonary disease were underutilized by this population.

Background: The present article presents equations for the prediction of coronary heart disease (CHD) in a population with high rates of diabetes and albuminuria, derived from data collected in the Strong Heart Study, a longitudinal study of cardiovascular disease in 13 American Indian tribes and communities in Arizona, North and South Dakota, and Oklahoma., Methods and Results: Participants of the Strong Heart Study were examined initially in 1989-1991 and were monitored with additional examinations and mortality and morbidity surveillance. CHD outcome data through December 2001 showed that age, gender, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, hypertension, and albuminuria were significant CHD risk factors. Hazard ratios for ages 65 to 75 years, hypertension, LDL cholesterol > or = 160 mg/dL, diabetes, and macroalbuminuria were 2.58, 2.01, 2.44, 1.66, and 2.11 in men and 2.03, 1.69, 2.17, 2.26, and 2.69 in women, compared with ages 45 to 54 years, normal blood pressure, LDL cholesterol <100 mg/dL, no diabetes, and no albuminuria. Prediction equations for CHD and a risk calculator were derived by gender with the use of Cox proportional hazards model and the significant risk factors. The equations provided good discrimination ability, as indicated by a c statistic of 0.70 for men and 0.73 for women. Results from bootstrapping methods indicated good internal validation and calibration., Conclusions: A "risk calculator" has been developed and placed on the Strong Heart Study Web site, which provides predicted risk of CHD in 10 years with input of these risk factors. This may be valuable for diverse populations with high rates of diabetes and albuminuria.

Background: Historically, prostate cancer mortality rates have been elevated in the U.S. Northern Plains states. The purpose of this study was to investigate possible contributing factors, especially whether there was any association with crop patterns., Methods: Prostate cancer mortality rates (1950-2000) in four northern plains states (MN, MT, ND, and SD) were compared to rates for 46 other U.S. states. Within the four states, county rates in urban, less urban, and rural areas also were compared. For additional analysis, urban counties and counties with <10% of county area in crops were excluded. The average percent of county area in total cropland 1930-1950 and 1954-1974 was estimated. Using Poisson regression, we investigated whether the average percentage of county area in total cropland, 1930-1950 and 1954-1974, was associated with prostate cancer mortality rates, 1975-2000, respectively. Poisson regression analyses were also used to evaluate associations between rates and major crops, which included spring and durum wheat, winter wheat, corn, and other crops. Population centroids of the Census 2000 block groups were used to estimate the percentage of males aged 35 and older residing in close proximity to small grains crops., Results: Mortality rates were higher in rural compared to urban counties in 1950-2000 (rate ratio [RR]=1.032; 95% CI=1.001-1.063). Rates in 1950-1974 were significantly associated with production of corn and other crops in 1930-1950 (corn: RR per 10% increase=1.033, 95% CI=1.012-1.054; other crops: RR=1.042, 95% CI=1.021-1.063). Mortality rates in 1975-2000 were significantly associated with spring and durum wheat production in 1954-1974 (RR per 10% increase=1.042, 95% CI=1.017-1.067). Prostate cancer mortality rates increased as the percentage of population living within 500 m of small grains crops increased., Conclusions: Epidemiologic studies to evaluate agricultural practices are warranted to further evaluate the observed associations.

Objective: To evaluate herd-level risk factors for seropositive status of cattle to 1 or more bluetongue viruses., Animals: 110 herds of cattle in Nebraska, North Dakota, and South Dakota., Procedure: Blood samples were collected before and after the vector season. Samples were tested for antibodies against bluetongue virus by use of a commercially available competitive ELISA. Factors evaluated included descriptors of geographic location and management practices. Trapping of insect vectors was conducted to evaluate vector status on a subset of 57 operations. A multivariable logistic regression model was constructed to evaluate associations., Results: For the full data set, altitude and latitude were associated with risk of having seropositive cattle (an increase in altitude was associated with an increase in risk, and a more northerly location was associated with a decrease in risk of a premise having seropositive cattle). Import of cattle from selected states was associated with an increase in risk of having seropositive cattle. From the subset of herds with data on vector trapping, altitude and latitude were associated with risk of having seropositive cattle, similar to that for the full model. However, commingling with cattle from other herds was associated with a decrease in risk of seropositivity., Conclusions and Clinical Relevance: Findings reported here may be useful in generating additional hypotheses regarding the ecologic characteristics of bluetongue viruses and other vector-borne diseases of livestock. Sentinel surveillance programs are useful for documenting regionalization zones for diseases, which can be beneficial when securing international markets for animals and animal products.

Echocardiographic left ventricular hypertrophy (Echo-LVH) and ST segment depression (STD) on the ECG have each been demonstrated to predict cardiovascular (CV) and all-cause (AC) mortality. However, the prognostic value of combining Echo-LVH and ECG-STD has not been examined. ECGs and echocardiograms were examined in 2193 American Indian participants in the second Strong Heart Study examination. STD was measured by computer and was considered abnormal if > or =50 microV. Echo-LVH was defined by indexed LV mass >116 g/m2 in men and >104 g/m2 in women. After a mean follow-up of 3.1+/-0.7 years, there were 57 CV and 169 AC deaths. In univariate Cox analyses, Echo-LVH (chi2=54.2 and chi2=68.5) and ECG-STD (chi2=35.9 and chi2=46.3, all P<0.001) predicted CV and AC mortality, respectively. The combination of Echo-LVH and ECG-STD improved risk stratification compared with either alone for both CV death (chi2=74.4, P<0.001) and AC death (chi2=102.0, P<0.001), with presence of both ECG-STD and Echo-LVH associated with the greatest risks. After adjustment for age, sex, and relevant risk factors, combined Echo-LVH and ECG-STD remained predictive of CV mortality (chi2=19.7, P<0.001) and AC mortality (chi2=24.9, P<0.001), with the presence of both Echo-LVH and ECG-STD associated with a 6.3-fold increased risk of CV death (95% CI: 2.8 to 14.2) and a 4.6-fold increased risk of AC mortality (95% CI: 2.5 to 8.5). ECG-STD and Echo-LVH additively increase the risk of both CV mortality and AC mortality. These findings support the value of combining Echo-LVH and ECG-STD to improve risk stratification. These findings require verification in other populations.

The Four-State Fetal Alcohol Syndrome (FAS) Consortium on the Studies of the Prevention of FAS is an effort to bring together resources, both human and material, across the states of Minnesota, Montana, North Dakota, and South Dakota to decrease the prevalence of births affected by prenatal alcohol exposure. Beginning in September 2000, the Consortium received 3 years of funding and operates through a cooperative agreement with funding from the Center for Substance Abuse Prevention (CSAP) at the Substance Abuse and Mental Health Services Administration (SAMHSA). Three primary objectives are addressed through the Consortium structure. These include: to develop and evaluate the formation of the Consortium itself; to develop an information base that systematizes data collection that helps determine populations and areas considered high risk; and to implement and test a scientific-based prevention/intervention model for women considered high risk of abusing alcohol during their childbearing years.

Background: Studies evaluating the relationship between smoking and cancer spread are limited., Methods: We studied the relationship between cancer stage at diagnosis (local, regional, or metastatic) and smoking history (current, previous, or nonsmoker). For lung cancer, patterns of spread were also studied., Results: In a tumor registry for eastern North Dakota, northwestern Minnesota, and northern South Dakota, 11,716 cases were identified from 1986 to 2001. Current smokers (relative risk [RR], 2.11; 95% confidence interval, 1.93 to 2.32; P <.001) and previous smokers (RR, 1.56; 95% confidence interval, 1.42 to 1.72; P <.001) had an increased risk of metastatic disease at diagnosis. Current smokers (RR, 1.39; 95% confidence interval, 1.29 to 1.51; P <.001), but not previous smokers, also had an increased risk of regional disease. An increase in metastatic disease was most evident for prostate cancer (RR, 1.53; P =.003). An increase in regional disease was most evident for head and neck (RR, 3.53; P <.001), prostate (RR, 1.83; P =.030), and breast cancer (RR, 1.22; P =.005). Compared with previous smokers, current smokers with metastatic lung cancer were more likely to have involvement of the brain (33.6% v 23.0%; P =.004), bone marrow, adrenal gland, and pericardium (24.7% v 15.9%; P =.004)., Conclusion: Previous or current smoking is a risk factor for increased cancer stage in a wide range of malignancies. Further study is required to determine whether this association is causal.

The aims of the Strong Heart Family Study are to clarify the genetic determinants of cardiovascular disease (CVD) risk in American Indians and to map and identify genes for CVD susceptibility. The authors describe the design of the Strong Heart Family Study (conducted between 1998 and 1999) and evaluate the heritabilities of CVD risk factors in American Indians from this study. In the first phase of the study, approximately 950 individuals, aged 18 years or more, in 32 extended families, were examined. The examination consisted of a personal interview, physical examination, laboratory tests, and an ultrasound examination of the carotid arteries. The phenotypes measured during the physical examination included anthropometry, lipoproteins, blood pressure, glycemic status, and clotting factors. Heritabilities for CVD risk factor phenotypes were estimated using a variance component approach and the program SOLAR. After accounting for the effects of covariates, the authors detected significant heritabilities for many CVD risk factor phenotypes (e.g., high density lipoprotein cholesterol (heritability = 0.50) and diastolic blood pressure (heritability = 0.34)). These results suggest that heredity explains a substantial proportion of the variability of CVD risk factors and that these heritabilities are large enough to warrant a search for major risk factor genes.

Objective: Alterations in carotid artery structure and function may represent phenotypic measures of vascular disease that contain information beyond that which can be inferred from conventional cardiovascular disease risk assessment. However, apart from their associations with cardiovascular disease risk factors and outcome, the genetic basis of variations in carotid artery structure and function is largely unknown. The purpose of this study was to examine the genetic and environmental contributions to carotid artery structure and function in 3 large groups of American Indians., Methods and Results: Approximately 950 men and women, aged > or =18 years, in 32 extended families were examined between 1997 and 1999. By use of a variance component approach and the program Sequential Oligogenic Linkage Analysis Routines, heritabilities for carotid artery structure and function phenotypes were estimated. After accounting for the effects of covariates (sex, age, diabetes, impaired glucose tolerance, smoking, cholesterol, body surface area, and hypertension), we detected significant heritabilities (given as h2 values) for common carotid artery diastolic diameter (h2<0.44), intimal-medial wall thickness (h2<0.21), vascular mass (h2<0.27), arterial stiffness (h2<0.23), and the augmentation index (h2<0.18)., Conclusions: These results suggest that the additive effects of genes explain a moderate proportion of the variability of carotid artery structure and function.

Background: Increased QT interval dispersion (QTd) is a proposed ECG marker of vulnerability to ventricular arrhythmias and of cardiovascular (CV) mortality. However, principal component analysis (PCA) of the T-wave vector loop may more accurately represent repolarization abnormalities than QTd., Methods and Results: Predictive values of QTd and PCA were assessed in 1839 American Indian participants in the first Strong Heart Study examination. T-wave loop morphology was quantified by the ratio of the second to first eigenvalues of the T-wave vector by PCA (PCA ratio); QTd was quantified as the difference between maximum and minimum QT intervals. After 3.7+/-0.9 years mean follow-up, there were 55 CV deaths. In univariate analyses, an increased PCA ratio predicted CV mortality in women (chi2=7.8, P=0.0053) and men (chi2=9.5, P=0.0021). In contrast, increased QTd was a significant predictor of CV mortality in women (chi2=30.6, P<0.0001) but not in men (chi2=2.0, P=NS). In multivariate Cox analyses controlling for risk factors and rate-corrected QT interval, the PCA ratio remained a significant predictor of CV mortality in women (chi2=4.0 P=0.043) and men (chi2=6.4, P=0.011); QTd was a significant predictor in women only (chi2=11.0, P=0.0009). PCA ratios >90th percentile (32% in women and 24.6% in men) identified women with a 3.68-fold increased risk of CV mortality (95% CI, 1.54 to 8.83) and men with a 2.77-fold increased risk (95% CI, 1.18 to 6.49)., Conclusions: Abnormalities of repolarization measured by PCA of the T-wave loop predict CV death in men and women, supporting use of PCA for quantifying repolarization abnormalities.

Pharmacologic treatment patterns for hypertensive American Indians from 13 communities in Arizona, Oklahoma, South Dakota, and North Dakota were assessed. Participants (2254 women and 1384 men, aged 48 to 79 years) completed a clinical examination between July 1993 and December 1995. The mean of two blood pressure (BP) measurements and detailed medication histories were obtained. The observed prevalence of hypertension was 46.7% (n=1698). In participants taking antihypertensive medications (n=1114), four principal drug classes were evaluated: diuretics, calcium channel blocking agents, beta-blocking agents, and angiotensin-converting enzyme (ACE) inhibitors. Among treated hypertensive participants, 71.4%, 24.6%, and 4.0% received one, two, and three medications, respectively. Among single drug regimens, ACE inhibitors (n=340) were used most often (49.4%), with calcium channel blocking agents and diuretics accounting for 24.2% and 19.9%, respectively. Although multiple drug class therapies varied, the combination of a diuretic and ACE inhibitor (n=120) accounted for 47.4% of dual therapy use. Hypertension control (SBP < 140 mm Hg, DBP < 90 mm Hg) rates were highest for those on dual therapies (65.4%), followed by participants on single (53.8%) and triple (43.6%) therapies. Among monotherapies, diuretics exhibited the best overall hypertension control rate in both diabetics (63.0%) and nondiabetics (68.0%), versus 47% to 61% for other remaining agents. The frequent use of ACE inhibitors, used singly or in combination, reflects the high prevalence of diabetes among American Indians. ACE inhibitors, combined with diuretics, were particularly useful in achieving BP control in this population.

Background: Nonspecific ST depression assessed by standard visual Minnesota coding (MC) has been demonstrated to predict risk. Although computer analysis has been applied to digital ECGs for MC, the prognostic value of computerized MC and computerized ST depression analyses have not been examined in relation to standard visual MC., Methods: The predictive value of nonspecific ST depression as determined by visual and computerized MC codes 4.2 or 4.3 was compared with computer-measured ST depression >or= 50 microV in 2,127 American Indian participants in the first Strong Heart Study examination. Computerized MC and ST depression were determined using separate computerized-ECG analysis programs and visual MC was performed by an experienced ECG core laboratory., Results: The prevalence of MC 4.2 or 4.3 by computer was higher than by visual analysis (6.4 vs 4.4%, P < 0.001). After mean follow-up of 3.7 +/- 0.9 years, there were 73 cardiovascular deaths and 227 deaths from all causes. In univariate Cox analyses, visual MC (relative risk [RR] 4.8, 95% confidence interval [CI] 2.6-9.1), computerized MC (RR 6.0, 95% CI 3.5-10.3), and computer-measured ST depression (RR 7.6, 95% CI 4.5-12.9) were all significant predictors of cardiovascular death. In separate multivariate Cox regression analyses that included age, sex, diabetes, HDL and LDL cholesterol, body mass index, systolic and diastolic blood pressure, microalbuminuria, smoking, and the presence of coronary heart disease, computerized MC (RR 3.0, 95% CI 1.6-5.6) and computer-measured ST depression (RR 3.1, 95% CI 1.7-5.7), but not visual MC, remained significant predictors of cardiovascular mortality. When both computerized MC and computer-measured ST depression were entered into the multivariate Cox regression, each variable provided independent risk stratification (RR 2.1, 95% CI 1.0-4.4, and RR 2.1, 95% CI 1.0-4.4, respectively). Similarly, computerized MC and computer-measured ST depression, but not visual MC, were independent predictors of all-cause mortality after controlling for standard risk factors., Conclusions: Computer analysis of the ECG, using computerized MC and computer-measured ST depression, provides independent and additive risk stratification for cardiovascular and all-cause mortality, and improves risk stratification compared with visual MC. These findings support the use of routine computer analysis of ST depression on the rest ECG for assessment of risk and suggest that computerized MC can replace visual MC for this purpose.

Objective: In 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association (ADA) recommended three new sets of criteria for the diagnosis of diabetes that were different from those established by the World Health Organization (WHO) in 1985. One of these three methods was based on a fasting plasma glucose value only. This article compares ADA criteria with WHO criteria by applying them to three subgroups of American Indians in the Strong Heart Study who had no known diabetes., Research Design and Methods: The Strong Heart Study is a prospective epidemiological study of vascular disease in three American Indian populations aged 45-74 years. During the baseline examination from 1988 to 1991, participants without diagnosed diabetes underwent a fasting glucose test and a 2-h oral glucose tolerance test. These values were used to compare the ADA and WHO diagnostic criteria., Results: By using fasting and 2-h glucose values, prevalence rates of undiagnosed diabetes were 15.9% according to WHO criteria and 14.4% according to ADA criteria. The overall agreement rate was 65%, and the weighted kappa statistic was 0.474, which indicates moderate agreement. The age-specific analysis showed that, among participants between 45 and 54 years of age, the prevalence rates of undiagnosed diabetes were 13.4% according to WHO criteria and 12.7% according to ADA criteria. Among those aged 55-74 years, the rates were 18.7% according to WHO criteria and 16.3% according to ADA criteria. Thus, the difference in the prevalence rates when using WHO and ADA criteria, although generally small in this population, was three times higher in the older group (2.4%) than the difference in the younger group (0.7%)., Conclusions: The Strong Heart Study found that prevalence rates of undiagnosed diabetes determined by ADA criteria and WHO criteria were similar in its American Indian population. The data suggest that the difference between the two criteria may increase as age increases. Longitudinal data will be needed to evaluate further the utility of the two criteria.

Objective: We used the Semmes-Weinstein 5.07 monofilament to assess the prevalence of foot insensitivity and its relationship to potential risk factors., Research Design and Methods: There were 3,638 American Indian participants from Arizona, North and South Dakota, and Oklahoma who attended a study clinic on two occasions: baseline and follow-up, 4 years later. Oral glucose tolerance tests were performed at the visits for those who had not previously been diagnosed as having diabetes. A total of 2,051 participants were diagnosed with diabetes before the study or at the subsequent study visits. At the follow-up visit, participants were tested for their ability to sense the 5.07 (10 g) monofilament at 10 sites of the foot. The prevalence of foot insensitivity was ascertained, and its relation to characteristics of participants was assessed in both univariate and logistic regression analyses., Results: Diabetic participants had a much higher prevalence of foot insensitivity (defined as greater than or equal to five incorrect responses) than nondiabetic participants (14 vs. 5%, respectively). However, marked foot insensitivity was uncommon within the first few years of diagnosis of diabetes. Among the diabetic participants, those diagnosed before study entry had the highest prevalence of foot insensitivity. The prevalence of foot insensitivity was highest in the Arizona Indians (22 vs. 9% in the Dakotas and 8% in Oklahoma). In a logistic regression analysis, foot insensitivity was significantly and independently related to center (Arizona versus others), age, duration of diabetes, and height., Conclusions: Marked foot insensitivity is prevalent in the diabetic American Indian population, especially in Indians in Arizona; however, this insensitivity is apparently uncommon for several years after the diagnosis of diabetes. The data show that Indians with diabetes are particularly vulnerable to the risk of foot ulceration and that the diagnostic screening of diabetes may lead to better prevention of sensory neuropathy and subsequent foot ulceration.

Background: Although cardiovascular disease (CVD) used to be rare among American Indians, Indian Health Service data suggest that CVD mortality rates vary greatly among American Indian communities and appear to be increasing. The Strong Heart Study was initiated to investigate CVD and its risk factors in American Indians in 13 communities in Arizona, Oklahoma, and South/North Dakota., Methods and Results: A total of 4549 participants (1846 men and 2703 women 45 to 74 years old) who were seen at the baseline (1989 to 1991) examination were subjected to surveillance (average 4.2 years, 1991 to 1995), and 88% of those remaining alive underwent a second examination (1993 to 1995). The medical records of all participants were exhaustively reviewed to ascertain nonfatal cardiovascular events that occurred since the baseline examination or to definitively determine cause of death. CVD morbidity and mortality rates were higher in men than in women and were similar in the 3 geographic areas. Coronary heart disease (CHD) incidence rates among American Indian men and women were almost 2-fold higher than those in the Atherosclerosis Risk in Communities Study. Significant independent predictors of CVD in women were diabetes, age, obesity (inverse), LDL cholesterol, albuminuria, triglycerides, and hypertension. In men, diabetes, age, LDL cholesterol, albuminuria, and hypertension were independent predictors of CVD., Conclusions: At present, CHD rates in American Indians exceed rates in other US populations and may more often be fatal. Unlike other ethnic groups, American Indians appear to have an increasing incidence of CHD, possibly related to the high prevalence of diabetes. In the general US population, the rising prevalence of obesity and diabetes may reverse the decline in CVD death rates. Therefore, aggressive programs to control diabetes and its risk factors are needed.

The high rate of infant mortality among native peoples in the Aberdeen Service Area of the Indian Health Service (primarily North and South Dakota) prompted a multi-institutional study of this problem. The study investigators assumed that local coroners or medical examiners would be able to perform suitable death scene investigations. However, during the design portion of the study it became apparent that, with one exception, none of the participating Indian Nations had a death investigator or even a legal mandate to provide death investigation. To allow the study to go forward, and ultimately to better the community health within its service area, the Aberdeen Area Indian Health Service submitted a draft enabling coroner legislation/resolutions to the area tribes. By November of 1996, 6 of the 19 Indian Nations enacted enabling coroner legislation. To facilitate both the study and general death investigation within the area, the Aberdeen Area Indian Health Service since 1993 has held five 2-day death investigation training programs covering a variety of death investigation topics which were attended by 68 participants. Without further recognition of the need for tribal death investigation and additional funding, these gains in tribal death investigation will probably be transitory.

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.

Community mortality surveillance for 1984-1988 was conducted by researchers of the Strong Heart Study, which examined the incidence, prevalence, and risk factors of cardiovascular disease in three American Indian populations, aged 45-74 years, in Arizona, Oklahoma, and South/North Dakota. All-cause and cardiovascular disease mortality rates were determined through the use of death certificate data. Cardiovascular disease deaths were confirmed by independent systematic review of medical records. In all three populations, men had higher all-cause and cardiovascular disease mortality rates than did women. Oklahoma exhibited slightly lower 5-year, age-adjusted, all-cause mortality (96/1,000) than did Arizona (107/1,000) and South/North Dakota (114/1,000). The leading cause of death among both sexes in Oklahoma and in South/North Dakota was cardiovascular disease. Diabetes mellitus led among Arizona women. The other major causes of death were cancer, liver disease including cirrhosis, and injury. When compared with the rates in each state, average annual all-cause mortality rates were higher for the American Indian populations in almost every age group. The all-cause annual mortality rates in the three Indian populations were close to rates in the US black population and higher than the rates of the entire US population and of US whites. This trend was amplified in the 45- to 64-year age group. Only in the 65- to 74-year age group did mortality rates in the Indian population approach those of the US population. Cardiovascular disease mortality rates were close to the US averages in Arizona and Oklahoma, but they were more than two times higher in South/North Dakota among those between 45 and 64 years of age. Thus, American Indians in Arizona, Oklahoma, and South/North Dakota exhibit high all-cause mortality rates. In particular, the South/North Dakota population cardiovascular disease death rate appears to present a potential target for community-based programs to intervene on known risk factors to promote healthy lifestyles.

Objective: To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry., Research Design and Methods: This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio., Results: A total of 4,549 eligible participants were examined, and diabetes status was determined for 4,304 (1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status., Conclusions: Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs should be expanded to include those with IGT to improve glycemic control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.

Community trials involve the assignment of intact social groups to study conditions and are becoming increasingly common in epidemiologic research. In both the design and analysis of these studies, whether cross-sectional or cohort, allowance must be made for the dependence of elements within intact groups if variances are to be properly estimated. In the design phase, the statistician needs estimates of the level of dependence likely to be encountered. In the analysis phase, external estimates of the level of dependence may be useful in preventing the erosion of power associated with small numbers of intact groups assigned to each condition. We report the intraclass correlation coefficients of the city-year component of variance as estimated in the Minnesota Heart Health Program for a variety of community survey variables and illustrate their use in both design and analysis. Of 23 variables assessed, all but two showed positive estimates of city-year intraclass correlations. In these data, estimates of intraclass correlation coefficients generally were in the range 0.002-0.012.

Objective: To determine the prevalence and incidence rates of diabetes and two specific complications for selected American-Indian tribes in North Dakota, South Dakota, and Nebraska., Research Design and Methods: A descriptive epidemiological study was conducted using ambulatory care data during 1987 for prevalence and diabetes registries and complication case reporting during 1988 from IHS facilities on reservations in these states., Results: The Winnebago and Omaha tribes had the highest age-adjusted diabetes rates, with prevalence 8.8 times and incidence 7.7 times the respective U.S. rates. The diabetes prevalence rate of combined data for the Sioux was 3.7 times the U.S. rate. Among Sioux Indians, the age-adjusted incidence rate for ESRD was 4.8 times the American-Indian/Alaska-Native rate and 13.4 times the rate for U.S. whites. The proportion of new diabetes-related ESRD (86%) was almost 3 times greater than the general U.S. population rate (30%). Also, among the Sioux, the age-adjusted incidence rate for LEA (86.7/10,000 diabetic population) was 1.5 times higher than the U.S. rate; the proportion of diabetes-related LEA (84%) was 1.8 times higher than the general U.S. population rate (45%)., Conclusions: The age-adjusted rates of diabetes and certain complications among these Northern Plains tribes are greater than the U.S. rates. Improved health services to detect and monitor diabetes and its complications and community-based prevention activities directed at the epidemic of diabetes among the various Indian tribes are urgently needed.

Secular trend in body mass index (BMI) over 7 years (1980-1987) was examined in the upper mid-western part of the USA using annual cross-sectional data collected by the Minnesota Heart Health Program. Significant secular increase in BMI adjusted for age and education was found in both men (0.08 kg/m2/year, P less than 0.02) and women (0.19 kg/m2/year, P less than 0.0001). In women, the secular increase occurred throughout the distribution of body weights but the change in the upper end was two to three times greater than that in the other parts of the distribution. In men, most of the increase in BMI occurred in the upper end of the distribution. Prevalence of obesity (defined as BMI greater than or equal to 85th percentile at year 1: men, 30.16 kg/m2; women, 29.94 kg/m2) increased by 0.6 percent/year (P = 0.1) in men and by 1.0 percent/year (P = 0.002) in women. The results indicate that body weight is increasing in upper mid-western adults, probably largely as a result of already overweight individuals becoming more obese. The secular increase in BMI was not accompanied by systemic change in reported food intake and exercise, and could not be explained by decreased prevalence of smoking. Large increases in body weight, especially among those who are already overweight, may have a significant public health impact.

From 1987 through 1988, a cluster of cases of tuberculosis (TB) occurred among persons residing on the Standing Rock Sioux Reservation; recognition of this cluster prompted an epidemiologic investigation by the Indian Health Service (IHS), Standing Rock Sioux Tribal Health and Community Health Programs, South Dakota State Department of Health, North Dakota State Department of Health, and CDC. This report summarizes the findings of that investigation and follow-up public health interventions.

This paper reports on the development and application of multiple risk-adjusted measures of hospital performance (mortality, readmission, complications). The indices are based on patient-level data so they can be aggregated at any level (hospital, specialty, physician), are easy to use and interpret by hospitals, and provide an inexpensive method for evaluating hospital performance using existing databases. This paper focuses on the development of practical applications of these measures in the quality improvement process.