Chiral separation of calcium channel antagonists by SFC and HPLC using different immobilized chiral stationary phases.

Supercritical fluid chromatography and high-performance liquid chromatography techniques are popular for the chiral separations of different drugs and pharmaceuticals. Therefore, this article describes a comparative study of the chiral separation of some calcium channel antagonists such as verapamil, gallopamil, and nisoldipine. The columns used were Chiralpak IG and Chiralpak ID (250 mm × 4.6 mm, 5.0 µm). The separation was achieved by using a variety of mobile phases in both techniques. The retention, separation, and resolution factors in SFC were in the range of 1.36-7.30, 1.09-1.72, and 1.16-3.47, while these values in the case of HPLC were 1.03-2.42, 1.12-1.35, and 0.49-2.46. The complete resolution of gallopamil and verapamil was achieved successfully. The chiral recognition was controlled by hydrogen bondings, π-π interactions, dipole induced dipole interactions, van der Waal forces, and steric effects. SFC was found to be a better technique than HPLC because of quick separation, good separation power, economic, environment-friendly, and green technology.

Chiral separation of ß-blockers by supercritical fluid chromatography using Chiralpak-IG and Chiralpak IBN-5 columns.

Chiral separation of ß-blockers is performed by utilizing the supercritical fluid chromatographic method. The chiral columns utilized were Chiralpak IG and Chiralpak IBN-5. The finest mobile phase was CO2 -0.2% TEA in methanol (60:40). The values atenolol enantiomers retention factors were 6.39 and 8.98. These values for propranolol enantiomers were 3.39 and 4.06. These values for betaxolol enantiomers were 4.08 and 4.68. The separation and resolution factor values for atenolol, propranolol, and betaxolol were 1.41 and 3.33, 1.19 and 2.23, and 1.15 and 1.87, separately and respectively. By comparison, it was observed that Chiralpak IG column is better than Chiralpak IBN-5 column. Supercritical fluid chromatography has been found as the best analytical technique due to its high speed, being eco-friendly, and being economic. The various most probable interactions responsible for the chiral resolution are hydrogen bonding, dipole-dipole interactions, steric effect, and π-π interactions. The reported methods are effective, efficient, and reproducible and may be used to separate and identify atenolol, propranolol, and betaxolol in any unknown samples.

Metal-Organic Precursor Synthesis, Structural Characterization, and Multiferroic Properties of GdFeO3 Nanoparticles.

GdFeO3 nanoparticles were fabricated by a facile metal-organic precursor method using citric acid as a complexing agent. The phase purity and structural analysis by powder X-ray diffraction and FTIR studies indicates that the material is highly crystalline with an orthorhombic structure. Electron microscopic (TEM and SEM) studies of rare earth ferrites reveal worm-shaped nanoparticles with an average grain size of 95 nm. The high-resolution TEM study provides an insightful image, which shows an interplanar spacing of approximately 0.12 nm that corresponds to the (112) crystalline plane. A high surface area of 231.5 m2 g-1 has been achieved with a mesoporous texture, which in turn gives a high dielectric constant. Well-defined hysteresis is obtained with a saturation magnetization of 17.5 emu g-1, remanent magnetization of 3.9 emu g-1, and coercive field of -446 Oe. Room-temperature ferroelectricity in GdFeO3 nanoparticles has been found for the first time with no leaky current and hence may be used in multistate memory devices.

Advances in novel drug delivery strategies for breast cancer therapy.

Breast cancer remains one of the world's most devastating diseases. However, better understanding of tumor biology and improved diagnostic devices could lead to improved therapeutic outcomes. Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Various nanocarriers have been introduced to improve the therapeutic efficacy of anticancer drugs, including liposomes, polymeric micelles, quantum dots, nanoparticles, and dendrimers. Recently, targeted drug delivery systems for anti-tumor drugs have demonstrated great potential to lower cytotoxicity and increase therapeutic effects. Various ligands/approaches have been explored for targeting breast cancer. This paper provides an overview of breast cancer, conventional therapy, potential of nanotechnology in management of breast cancer, and rational approaches for targeting breast cancer.

Immunopolymer Lipid Nanoparticles for Delivery of Macromolecules to Antigen-Expressing Cells.

Macromolecules such as antibodies and antibody fragments have been reported to interfere with intracellular targets, but their use is limited to delivery systems where expression is achieved from vectors such as plasmids or viruses. We have developed PEGylated nanoparticles of poly-lactic acid (PLA), including the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which are functionalized with monoclonal anti-CD7, anti-CD53, or anti-GPR56 antibodies for receptor-mediated endocytic delivery into T-cell leukemia cell lines. Incorporation of DOTAP as the lipid component of the PLA nanoparticles enhanced the release of the immuno-nanoparticles from the endosomes into the cytosol compared to nanoparticles made from PLA alone. Systemic delivery of these anti-CD7 immuno-nanoparticles into humanized CD7 transgenic mice resulted in localization in the spleen, enhanced uptake into CD7-expressing splenocytes, and release of low amounts of reporter mRNA for translation. These functionalized polymer lipid nanoparticles are the basis for elaboration and optimization for realizing their potential in therapeutic applications to carry specific macromolecules such as mRNAs for translation into therapeutic proteins that can target intracellular proteins which mediate disease.

Race and sex differences in the receipt of timely and appropriate lung cancer treatment.

BACKGROUND: Previous research suggests that disparities in non-small-cell lung cancer (NSCLC) survival can be explained in part by disparities in the receipt of cancer treatment. Few studies, however, have considered race and sex disparities in the timing and appropriateness of treatment across stages of diagnosis. OBJECTIVE: To evaluate the relationship of sex and race with the receipt of timely and clinically appropriate NSCLC treatment for each stage of diagnosis. METHOD: Surveillance Epidemiology and End Result data linked to Medicare claims for beneficiaries diagnosed with NSCLC between 1995 and 1999 were used to evaluate the relationship between race and sex with timely and appropriate NSCLC treatment while controlling for other demographic characteristics, comorbidities, socioeconomic status, and provider supply (N = 22,145). RESULTS: Overall adjusted rates of timely and appropriate treatment are 37.2%, 58.1%, and 29.2% for Medicare beneficiaries diagnosed with stage I or II, III, and IV NSCLC, respectively. Among stage I or II patients, women were 25% less likely to receive timely surgical resection relative to men, and blacks were 66% less likely to receive timely and appropriate treatment than whites. Black men were least likely to receive resection (22.2% compared with 43.7% for white men). Blacks were 34% less likely to receive timely surgery, chemotherapy, or radiation for stage III disease and were 51% less likely to receive chemotherapy in a timely fashion for stage IV disease relative to whites. CONCLUSION: Significant variations in appropriate timely treatment were found within and across stages of diagnosis, confirming that sex and race differences in NSCLC treatment exist.

Who gets disease management?

BACKGROUND: Disease management (DM) has been promoted to improve health outcomes and lower costs for patients with chronic disease. Unfortunately, most of the studies that support claims of DM's success suffer from a number of biases, the most important of which is selection bias, or bias in the type of patients enrolling. OBJECTIVE: To quantify the differences between those who do and do not enroll in DM. DESIGN, SETTING, AND PARTICIPANTS: This was an observational study of the health care use, costs, and quality of care of 27,211 members of a large health insurer who were identified through claims as having asthma, diabetes, or congestive heart failure, were considered to be at high risk for incurring significant claims costs, and were eligible to join a disease management program involving health coaching. MEASUREMENTS: We used health coach call records to determine which patients participated in at least one coaching call and which refused to participate. We used claims data for the 12 months before the start of intervention to tabulate costs and utilization metrics. In addition, we calculated HEDIS quality scores for the year prior to the start of intervention. RESULTS: The patients who enrolled in the DM program differed significantly from those who did not on demographic, cost, utilization and quality parameters prior to enrollment. For example, compared to non-enrollees, diabetes enrollees had nine more prescriptions per year and higher HbA1c HEDIS scores (0.70 vs. 0.61, p < 0.001). CONCLUSIONS: These findings illuminate the serious problem of selection into DM programs and suggest that the effectiveness levels found in prior evaluations using methodologies that don't address this may be overstated.

Early detection of influenza outbreaks using the DC Department of Health's syndromic surveillance system.

BACKGROUND: Since 2001, the District of Columbia Department of Health has been using an emergency room syndromic surveillance system to identify possible disease outbreaks. Data are received from a number of local hospital emergency rooms and analyzed daily using a variety of statistical detection algorithms. The aims of this paper are to characterize the performance of these statistical detection algorithms in rigorous yet practical terms in order to identify the optimal parameters for each and to compare the ability of two syndrome definition criteria and data from a children's hospital versus vs. other hospitals to determine the onset of seasonal influenza. METHODS: We first used a fine-tuning approach to improve the sensitivity of each algorithm to detecting simulated outbreaks and to identifying previously known outbreaks. Subsequently, using the fine-tuned algorithms, we examined (i) the ability of unspecified infection and respiratory syndrome categories to detect the start of the flu season and (ii) how well data from Children's National Medical Center (CNMC) did versus all the other hospitals when using unspecified infection, respiratory, and both categories together. RESULTS: Simulation studies using the data showed that over a range of situations, the multivariate CUSUM algorithm performed more effectively than the other algorithms tested. In addition, the parameters that yielded optimal performance varied for each algorithm, especially with the number of cases in the data stream. In terms of detecting the onset of seasonal influenza, only "unspecified infection," especially the counts from CNMC, clearly delineated influenza outbreaks out of the eight available syndromic classifications. In three of five years, CNMC consistently flags earlier (from 2 days up to 2 weeks earlier) than a multivariate analysis of all other DC hospitals. CONCLUSIONS: When practitioners apply statistical detection algorithms to their own data, fine tuning of parameters is necessary to improve overall sensitivity. With fined tuned algorithms, our results suggest that emergency room based syndromic surveillance focusing on unspecified infection cases in children is an effective way to determine the beginning of the influenza outbreak and could serve as a trigger for more intensive surveillance efforts and initiate infection control measures in the community.

An exploration of urban and rural differences in lung cancer survival among medicare beneficiaries.

OBJECTIVES: We tested the relationship between urban or rural residence as defined by rural-urban commuting area codes and risk of mortality in a sample of Medicare beneficiaries with lung cancer. METHODS: We used Surveillance, Epidemiology, and End Results data linked with Medicare claims to build proportional hazards models. The models tested hypothesized relationships between individual and community characteristics and overall survival for a cohort of Medicare beneficiaries 65 years and older who were diagnosed with lung cancer between 1995 and 1999 (N=26073). RESULTS: We found no evidence that lung cancer patients in rural areas have poorer survival than those in urban areas. Rather, individual (Medicaid coverage) and regional (lower census tract-level median income) socioeconomic factors and a smaller supply of subspecialists per 10000 individuals 65 years and older were positively associated with a higher risk of mortality. CONCLUSIONS: Although urban versus rural residence did not directly influence survival, rural residents were more likely to live in poorer areas with a smaller supply of health care providers. Therefore, we still need to be aware of rural beneficiaries' potential disadvantage when it comes to receiving needed care in a timely fashion.

Hospital competition, managed care, and mortality after hospitalization for medical conditions in California.

OBJECTIVE: To assess the effect of hospital competition and health maintenance organization (HMO) penetration on mortality after hospitalization for six medical conditions in California. DATA SOURCE: Linked hospital discharge and vital statistics data for short-term general hospitals in California in the period 1994-1999. The study sample included adult patients hospitalized for one of the following conditions: acute myocardial infarction (N=227,446), hip fracture (N=129,944), stroke (N=237,248), gastrointestinal hemorrhage (GIH, N=216,443), congestive heart failure (CHF, N=355,613), and diabetes (N=154,837). STUDY DESIGN: The outcome variable was 30-day mortality. We estimated multivariate logistic regression models for each study condition with hospital competition, HMO penetration, hospital characteristics, and patient severity measures as explanatory variables. PRINCIPAL FINDINGS: Higher hospital competition was associated with lower 30-day mortality for three to five of the six study conditions, depending on the choice of competition measure, and this finding was robust to a variety of sensitivity analyses. Higher HMO penetration was associated with lower mortality for GIH and CHF. CONCLUSIONS: Hospitals that faced more competition and hospitals in market areas with higher HMO penetration provided higher quality of care for adult patients with medical conditions in California. Studies using linked hospital discharge and vital statistics data from other states should be conducted to determine whether these findings are generalizable.

Effect of disease management on prescription drug treatment: what is the right quality measure?

Measures of medication adherence have become common parameters with which disease management (DM) programs are being evaluated, leading to the question of how this concept should be measured in the particular context of a DM intervention. We hypothesize that DM improves adherence to prescriptions more than the rate with which prescriptions are being filled. We used health plan claims data to construct 13 common measures of medication adherence for five chronic conditions. The measures were operationalized in three different ways: the Prescription Fill Rate (PFR), which requires only one prescription; the Medication Possession Ratio (MPR), which requires a supply that covers at least 80% of the year; and the Length of Gap (LOG), which requires no gap greater than 30 days between prescriptions. We compared results from a baseline year to results during the first year of a DM program. Changes in adherence were quite small in the first year of the intervention, with no changes greater than six percentage points. In the intervention year, three measures showed a significant increase based on all three operational definitions, but two measures paradoxically decreased based on the PFR. For both, the MPR and the LOG suggested either no change or significant improvement. None of the MPR and LOG measures pointed toward significantly lower compliance in the intervention year. Different ways to operationalize the concept of medication adherence can lead to fundamentally different conclusions. While more complex, MPR- and LOG-based measures could be more appropriate for DM evaluation. Our initial results, however, need to be confirmed by data covering longer term follow-up.

Synchronized Fast SPE and UFLC Methods for the Analyses of Eight Antidiabetic Drugs in Human Plasma.

AIM AND OBJECTIVE: The population of diabetic patients is rapidly increasing globally. The treatment of these patients is a complex phenomenon due to the use of the different drugs. The present article reports a synchronized fast SPE-UFLC separation of eight antidiabetic drugs in human plasma. Inexpensive solid phase extraction (SPE) and ultra fast liquid chromatography (UFLC) methods were presented for monitoring of eight antidiabetic drugs in human plasma. The separated drugs include metformin HCl, vildagliptin, gliclazide, linagliptin, sitagliptin, pioglitazone, glimepiride and repaglinide plasma sample. MATERIAL AND METHOD: The column used was a Sunshell C18 (150 x 4.6 mm, 2.6 µ) with eluent of acetate buffer (0.05% TEA in 0.05 M NH4Ac of pH 7.0 with H 3PO4) - ACN (60 : 40, v/v). The flow rate was 1.0 mL/min with a detection wavelength of 210 nm and column temp. of 45±1ºC. These drugs were extracted from human plasma using Sep-Pac C18 cartridge. Phosphate buffer (25 mM; pH 7.0) containing these drugs were allowed to pass through cartridge at 0.1 mL/min flow rate. The adsorbed drugs on C18 cartridge were eluted by methanol at 1.0 mL/min flow rate. RESULTS: The values for the retention, separation and resolution factors were ranged from 0.072 to 9.140, 1.443 to 4.208 and 2.147 to 18.652, correspondingly. The percent recoveries for these drugs in the standard laboratory samples prepared in water ranged from 77 to 88%. These values in plasma samples ranged from 10 to 22%. CONCLUSION: The validated method was fruitfully adopted to analyze these drugs in human plasma for the clinical monitoring of these drugs.

Racial and ethnic disparities in care: the perspectives of cardiologists.

BACKGROUND: Despite extensive documentation of racial and ethnic disparities in care, provider awareness of disparities has been thought to be low. To be effective, educational efforts for physicians must consider providers' knowledge and beliefs about what causes disparities and what can be done about them. METHODS AND RESULTS: We conducted a Web-based survey of 344 cardiologists to determine their level of awareness of disparities and views of underlying causes. Responses were assessed by means of 5-point Likert scales. Thirty-four percent of cardiologists agreed that disparities existed in care overall in the US healthcare system, and 33% agreed that disparities existed in cardiovascular care. Only 12% felt disparities existed in their own hospital setting, and even fewer, 5%, thought disparities existed in the care of their own patients. Despite this, most respondents rated the strength of the evidence about disparities as "very strong" or "strong." Respondents identified many potential causes for disparities in care but were more likely to endorse patient and system level factors (eg, insurance status or adherence) rather than provider level factors. CONCLUSIONS: Cardiologists' awareness of disparities in care remains low, and awareness is inversely proportional to proximity to their own practice setting.

Hospital competition, managed care, and mortality after hospitalization for medical conditions: evidence from three states.

This study assessed the effect of hospital competition and HMO penetration on mortality after hospitalization for six medical conditions in California, New York, and Wisconsin. We used linked hospital-discharge and vital-statistics data to study adults hospitalized for myocardial infarction, hip fracture, stroke, gastrointestinal hemorrhage, congestive heart failure, or diabetes. We estimated logistic regression models with death within 30 days of admission as the dependent variable and hospital competition, HMO penetration, and hospital and patient characteristics as explanatory variables. Higher hospital competition was associated with lower mortality in California and New York but not Wisconsin. Higher HMO penetration was associated with lower mortality in California but higher mortality in New York. These findings suggest that hospitals in highly competitive markets compete on quality even in the absence of mature managed-care markets. The findings also underscore the need to consider geographic effects in studies of market structure and hospital quality.

Use of an electronic monitoring system for self-reporting smallpox vaccine reactions.

OBJECTIVES: Tracking vaccine reactions and adverse events during a large-scale vaccination program such as the recent smallpox program or a pandemic flu outbreak will be a challenge. We report on vaccine reaction data collected using a novel telephone- and web-based electronic reporting system. The system was used to monitor vaccinees during the U.S. Army's smallpox vaccination campaign, which was part of the national program to prepare against biological attack. In addition, we report on the time course of events after smallpox vaccination based on the self-reported data and evaluate the validity and reliability of self-reported take information after smallpox vaccination. METHODS: A prospective cohort of subjects receiving the smallpox vaccination volunteered to use an electronic monitoring system to track and report their vaccination reactions. RESULTS: Users made 6.8 +/- 6.2 (mean +/- SD) reports using the electronic monitoring system. The sensitivity and positive predictive value of self-reported takes were high, 98.8% and 99.6%, respectively. The vaccination-site reactions progressed faster for revaccinees than first-time vaccinees. CONCLUSIONS: Simple-to-use telephone/Internet-based technology allowed detailed self-recording of response to smallpox vaccination among outpatients. Self-reports on site appearance were sufficient to determine vaccine takes in most vaccinees. During a mass vaccination event, an electronic monitoring system could facilitate tracking of vaccine reactions, including providing an early warning system for adverse events, and might reduce the burden associated with follow-up visits with healthcare professionals.

Drink-driving and DUI recidivists' attitudes and beliefs: a longitudinal analysis.

OBJECTIVE: Cross-sectional survey research has shown correlations between drink-driving behavior and people's beliefs concerning the riskiness, social acceptability and morality of driving under the influence of alcohol. The current study examines the association between such beliefs and subsequent alcohol-impaired driving in a sample of offenders who were driving under the influence (DUI). METHOD: Repeated interviews were conducted with 182 multiple DUI offenders. Baseline data included measures of moral and prescriptive beliefs concerning alcohol-impaired driving (internal behavioral controls), perceived risks of criminal punishment and crashes associated with alcohol-impaired driving (external behavioral controls) and perceived peer-group attitudes toward alcohol-impaired driving (social control). The dependent variable in the study was a measure of self-reported alcohol-impaired driving over the preceding 2 years, collected at 2-year follow-up from baseline. RESULTS: Results from multiple regression modeling showed significant protective effects associated with the beliefs that driving after drinking is immoral and that random police sobriety checks are a good idea (internal control items). Results also showed that a social desirability control measure was predictive of increased risk, at follow-up, for driving after drinking. CONCLUSIONS: These results suggest that internal controls may protect against alcohol-impaired driving behavior, even in a high-risk sample of repeat DUI offenders. The results also suggest that future policy interventions to curtail drink-driving might profitably be designed to promote these sorts of behavioral controls.

Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease in nondiabetic american indians: the Strong Heart Study.

OBJECTIVE: Insulin resistance (IR) and the metabolic syndrome (MS) are associated with type 2 diabetes and adverse cardiovascular disease (CVD) risk factor profiles. Whether IR and MS predict CVD independently of diabetes and other CVD risk factors is not known. This study examines whether IR and/or presence of MS are independently associated with CVD in nondiabetic American Indians (AI). RESEARCH DESIGN AND METHODS: We examined 2283 nondiabetic AI who were free of CVD at the baseline examination of the Strong Heart Study (SHS). CVD risk factors were measured, IR was quantified using the homeostasis model assessment (HOMA), and MS as defined by the National Cholesterol Education Program Adult Treatment Panel (ATP III) was assessed for each participant. Incident CVD and diabetes were ascertained during follow-up. RESULTS: MS was present in 798 individuals (35%), and 181 participants (7.9%) developed CVD over 7.6 +/- 1.8 years of follow-up. Age, BMI, waist circumference, and triglyceride levels increased and HDL cholesterol decreased across tertiles of HOMA-IR. Risk of diabetes increased as a function of baseline HOMA-IR (6.3, 14.6, and 30.1%; P < 0.001) and MS (12.8 vs. 24.5%). In Cox models adjusted for CVD risk factors, risk of CVD did not increase either as a function of baseline HOMA-IR or MS, but individual CVD risk factors predicted subsequent CVD. CONCLUSIONS: Among nondiabetic AI in the SHS, HOMA-IR and MS both predict diabetes, but neither predicts CVD independently of other established CVD risk factors.

Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes: the strong heart study.

OBJECTIVE: To determine whether non-HDL cholesterol, a measure of total cholesterol minus HDL cholesterol, is a predictor of CVD in patients with diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study, a population-based study of CVD and its risk factors in 13 American Indian communities in three geographic areas in the U.S. The baseline examination, conducted between July 1989 and January 1992, consisted of a personal interview, a physical examination, and laboratory tests. Of the 4,549 women and men aged 45-74 years participating in the study, 2,108 had diabetes but no CVD at baseline. Data on fatal and nonfatal CVD were collected during the follow-up period through 31 December 1998 (average 9 years). RESULTS: Multivariable analyses indicated that non-HDL cholesterol is a strong predictor of CVD in men and women with diabetes and is particularly indicative of coronary events. Hazard ratios for the highest tertile of non-HDL cholesterol in men and women with diabetes (2.23 and 1.80, respectively) were higher than those for either LDL cholesterol or triglycerides alone in both men and women and were higher than the ratio of total/HDL cholesterol in women. The utility of non-HDL cholesterol in predicting CVD extended over a wide range of triglyceride concentrations. CONCLUSIONS: This study suggests that non-HDL cholesterol index may be particularly useful in predicting CVD risk in patients with diabetes.

Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.

We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

Effects of isolated post-challenge hyperglycemia on mortality in American Indians: the Strong Heart Study.

PURPOSE: To assess the effects of isolated post-challenge hyperglycemia (IPH) on risk of cardiovascular disease (CVD), cancer, and all-cause mortality in American Indians using longitudinal data from the Strong Heart Study. METHODS: Of 4549 American Indian women and men aged 45 to 74 years participating in the Strong Heart Study, 4304 had fasting blood measurements or oral glucose tolerance test (OGTT) data to ascertain diabetes status. At baseline and follow-up, a personal interview was conducted, and physical examinations and laboratory tests were performed. Fasting blood samples were drawn for measurement of glucose, fibrinogen, insulin, lipids, lipoproteins, creatinine, and hemoglobin A1c (HbA1c). A 75-g OGTT was performed. Five diabetes categories were defined: (i) known diabetes, (ii) newly diagnosed diabetes (fasting glucose > or =126 mg/dL and no history of diabetes or diabetes medication; ADA-new diabetes), (iii) IPH, (iv) impaired fasting glucose (> or =110 - <126 mg/dL; IFG), and (v) normal fasting glucose (<110 mg/dL; NFG). Surveillance was initiated to determine CVD, cancer, and all-cause mortality over 9 years. RESULTS: IPH had a worse CVD risk factor profile than NFG, but IPH was associated with a better CVD risk factor profile than known diabetes or ADA-new diabetes. At follow-up, individuals with IFG had no increased risk for CVD or all-cause mortality, whereas those with ADA-new or known diabetes had significantly increased risk (RR = 1.70 and 1.40 for ADA-new diabetes, and RR = 2.87 and 2.19 for known diabetes, respectively). Those with IPH had nonsignificant elevations in risk for CVD (RR = 1.54) and all-cause (RR = 1.27) mortality. Cancer mortality was not increased in those with IFG, IPH, ADA-new diabetes, or known diabetes compared to those with NFG. CONCLUSIONS: Among American Indians 45 to 74 years of age, IPH is associated with nonsignificant elevations in total and CVD mortality. The magnitude of mortality risk associated with IPH is intermediate between diabetes and IFG. Because those with IPH are at high risk for diabetes, American Indians with IPH should be targeted for diabetes prevention.