Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus.

BACKGROUND: Measurement of carotid intima-media thickness (CIMT) has been validated as a measure of atherosclerosis and as a predictor of future cardiovascular events. Compared with glimepiride, pioglitazone has been shown to slow the progression of atherosclerosis measured by CIMT in patients with type 2 diabetes mellitus. METHODS AND RESULTS: We evaluated individual cardiovascular risk factors as predictors of the change in CIMT produced by pioglitazone treatment by determining whether their addition to a baseline model resulted in loss of significance for the treatment effect on CIMT. Pioglitazone treatment led to improvement in levels of multiple cardiovascular risk markers, including high-sensitivity C-reactive protein, apolipoprotein B, apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, triglyceride, insulin, and free fatty acid. At 24 weeks, there were significant differences in HDL cholesterol, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin, body mass index, hip circumference, and high-sensitivity C-reactive protein between the pioglitazone and glimepiride treatment groups. After adjustment for 24-week on-treatment values of cardiovascular risk factors, only inclusion of the changes in HDL cholesterol and insulin significantly impacted the magnitude and significance of the treatment effect on CIMT. Furthermore, irrespective of treatment assignment, increased HDL cholesterol at 24 weeks was a significant predictor of reduced CIMT progression at 72 weeks. CONCLUSIONS: The beneficial effect of pioglitazone on HDL cholesterol at 24 weeks predicted its beneficial effect for reducing CIMT progression at 72 weeks. Changes in HDL cholesterol at 24 weeks, irrespective of treatment, predicted less progression of CIMT at 72 weeks. These results suggest that suppression of atherosclerosis with pioglitazone therapy is linked to its ability to raise HDL cholesterol.

Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes.

We evaluated correlates of coronary atherosclerosis, measured by coronary artery calcium, in a racially diverse group of male and female subjects with type 2 diabetes. Age, systolic blood pressure, sex, and race/ethnicity were significant determinants of coronary artery calcium. Among lipoproteins, cholesterol level contained in a particle excluded from direct measures of LDL and HDL cholesterol (designated triglyceride-rich lipoprotein cholesterol) was most strongly linked to coronary artery calcium. Neither inflammatory markers nor metabolic factors correlated with coronary artery calcium in models adjusted for age and sex, but measures of adipose distribution did. Waist-to-hip ratio and the ratio of visceral to total abdominal tissue were positively associated with coronary artery calcium. In fully adjusted multivariate models, the relationship of adiposity measures to coronary artery calcium was no longer significant after inclusion of apolipoprotein B or triglyceride-rich lipoprotein cholesterol. Traditional risk factors and race/ethnicity remain important correlates of coronary artery calcium in a cohort at elevated risk of cardiovascular disease because of type 2 diabetes. Adiposity measures are significantly associated with coronary artery calcium score, but their importance may be largely explained by apolipoprotein B or triglyceride-rich lipoprotein cholesterol.

Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis.

BACKGROUND: The effect of different classes of antihypertensive drugs on incident diabetes mellitus is controversial because traditional meta-analyses are hindered by heterogeneity across trials and the absence of trials comparing angiotensin-converting-enzyme (ACE) inhibitors with angiotensin-receptor blockers (ARB). We therefore undertook a network meta-analysis, which accounts for both direct and indirect comparisons to assess the effects of antihypertensive agents on incident diabetes. METHODS: We undertook a systematic review up to Sept 15, 2006, and identified 48 randomised groups of 22 clinical trials with 143,153 participants who did not have diabetes at randomisation and so were eligible for inclusion in our analysis. 17 trials enrolled patients with hypertension, three enrolled high-risk patients, and one enrolled those with heart failure. The main outcome was the proportion of patients who developed diabetes. FINDINGS: Initial drug therapy used in the trials (and the number of patients with diabetes of the total number at risk) included: an ARB (1189 of 14,185, or 8.38%), ACE inhibitor (1618 of 22,941, or 7.05%), calcium-channel blocker (CCB, 2791 of 38,607, or 7.23%), placebo (1686 of 24,767, or 6.81%), beta blocker (2705 of 35,745, or 7.57%), or diuretic (998 of 18,699, or 5.34%). With an initial diuretic as the standard of comparison (eight groups), the degree of incoherence (a measure of how closely the entire network fits together) was small (omega=0.000017, eight degrees of freedom). The odds ratios were: ARB (five groups) 0.57 (95% CI 0.46-0.72, p<0.0001); ACE inhibitor (eight groups) 0.67 (0.56-0.80, p<0.0001); CCB (nine groups): 0.75 (0.62-0.90, p=0.002); placebo (nine groups) 0.77 (0.63-0.94, p = 0.009); beta blocker (nine groups) 0.90 (0.75-1.09, p=0.30). These estimates changed little in many sensitivity analyses. INTERPRETATION: The association of antihypertensive drugs with incident diabetes is therefore lowest for ARB and ACE inhibitors followed by CCB and placebo, beta blockers and diuretics in rank order.

Menopause transition stage and endogenous estradiol and follicle-stimulating hormone levels are not related to cognitive performance: cross-sectional results from the study of women's health across the nation (SWAN).

BACKGROUND: By one estimate, 60% of women experiencing the menopause transition perceive that they have memory problems, but most studies that have used cognitive function tests have not substantiated a relation between menopause stage and cognitive performance. We sought to describe the cross-sectional relation between menopause status, estradiol (E(2)), follicle-stimulating hormone (FSH), and measured cognitive function. METHODS: Cross sectional analysis of a community-based cohort of midlife women was used. Cognitive tests were the East Boston Memory Test, Symbol Digit Modalities, and Digits Span Backward. Menopause categories (premenopausal, early perimenopausal, late perimenopausal, and postmenopausal) were defined based on menstrual patterns. One set of general linear models assessed the relations between each cognitive test and menopause transition category, initially adjusted for age, race/ethnicity, education, symptoms, self-rated general health, and body mass index (BMI); next, these were additionally adjusted for FSH and E(2). A second set of models, stratified by menopause status, examined the possible relations between each cognitive test and either E(2) or FSH, adjusted for age, race/ethnicity, education, symptoms, self-related general health, and BMI. RESULTS: The mean age of the analytical sample (n = 1657) was 49.7 years. Only 5% of the sample had less than a high school education, 16% graduated from high school, and the rest had at least some college. The percent of women in each menopause category was premenopausal (9.0%), early perimenopausal (57.0%), late perimenopausal (13.4%), postmenopausal (20.6%). Although clinical-site adjusted models showed moderate differences between menopause transition groups and cognitive performance, no association was found between each of the measured cognitive performance tests and menopause transition status when adjusting for covariates. Similarly, no association between each cognitive test and E(2) or FSH was found. CONCLUSIONS: This study does not support a cross-sectional relation between cognitive test performance and menopause stage, FSH, or E(2).

Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial.

CONTEXT: Carotid artery intima-media thickness (CIMT) is a marker of coronary atherosclerosis and independently predicts cardiovascular events, which are increased in type 2 diabetes mellitus (DM). While studies of relatively short duration have suggested that thiazolidinediones such as pioglitazone might reduce progression of CIMT in persons with diabetes, the results of longer studies have been less clear. OBJECTIVE: To evaluate the effect of pioglitazone vs glimepiride on changes in CIMT of the common carotid artery in patients with type 2 DM. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, comparator-controlled, multicenter trial in patients with type 2 DM conducted at 28 clinical sites in the multiracial/ethnic Chicago metropolitan area between October 2003 and May 2006. The treatment period was 72 weeks (1-week follow-up). CIMT images were captured by a single ultrasonographer at 1 center and read by a single treatment-blinded reader using automated edge-detection technology. Participants were 462 adults (mean age, 60 [SD, 8.1] years; mean body mass index, 32 [SD, 5.1]) with type 2 DM (mean duration, 7.7 [SD, 7.2] years; mean glycosylated hemoglobin [HbA1c] value, 7.4% [SD, 1.0%]), either newly diagnosed or currently treated with diet and exercise, sulfonylurea, metformin, insulin, or a combination thereof. INTERVENTIONS: Pioglitazone hydrochloride (15-45 mg/d) or glimepiride (1-4 mg/d) as an active comparator. MAIN OUTCOME MEASURE: Absolute change from baseline to final visit in mean posterior-wall CIMT of the left and right common carotid arteries. RESULTS: Mean change in CIMT was less with pioglitazone vs glimepiride at all time points (weeks 24, 48, 72). At week 72, the primary end point of progression of mean CIMT was less with pioglitazone vs glimepiride (-0.001 mm vs +0.012 mm, respectively; difference, -0.013 mm; 95% confidence interval, -0.024 to -0.002; P = .02). Pioglitazone also slowed progression of maximum CIMT compared with glimepiride (0.002 mm vs 0.026 mm, respectively, at 72 weeks; difference, -0.024 mm; 95% confidence interval, -0.042 to -0.006; P = .008). The beneficial effect of pioglitazone on mean CIMT was similar across prespecified subgroups based on age, sex, systolic blood pressure, duration of DM, body mass index, HbA(1c) value, and statin use. CONCLUSION: Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00225264

Depressive symptoms, insulin resistance, and risk of diabetes in women at midlife.

OBJECTIVE: To examine depression and 3-year change in insulin resistance and risk of diabetes and whether associations vary by race. RESEARCH DESIGN AND METHODS: We analyzed data from 2,662 Caucasian, African-American, Hispanic, Japanese-American, and Chinese-American women without a history of diabetes from the Study of Women's Health Across the Nation. We estimated regression coefficients and odds ratios to determine whether depression (Center for Epidemiological Studies Depression Scale score > or =16) predicted increases in homeostasis model assessment of insulin resistance (HOMA-IR) and greater risk of incident diabetes, respectively, over 3 years. RESULTS: Mean baseline HOMA-IR was 1.31 (SD 0.86) and increased 0.05 units per year for all women (P <0.0001). A total of 97 incident cases of diabetes occurred. Depression was associated with absolute levels of HOMA-IR (P <0.04) but was unrelated to changes in HOMA-IR; associations did not vary by race. The association between depression and HOMA-IR was eliminated after adjustment for central adiposity (P=0.85). Depression predicted a 1.66-fold greater risk of diabetes (P <0.03), which became nonsignificant after adjustment for central adiposity (P=0.12). We also observed a depression-by-race interaction (P <0.05) in analyses limited to Caucasians and African Americans, the only groups with enough diabetes cases to reliably test this interaction. Race-stratified models showed that depression predicted 2.56-fold greater risk of diabetes in African Americans only, after risk factor adjustment (P=0.008). CONCLUSIONS: Depression is associated with higher HOMA-IR values and incident diabetes in middle-aged women. These associations are mediated largely through central adiposity. However, African-American women with depression experience increased risk of diabetes independent of central adiposity and other risk factors.

Role of surrogate markers in assessing patients with diabetes mellitus and the metabolic syndrome and in evaluating lipid-lowering therapy.

Diabetes mellitus and the metabolic syndrome (MS) are reaching epidemic proportions in the United States, and cardiovascular disease continues to be the leading cause of death among patients with diabetes. A range of noninvasive screening tools may help reduce the morbidity and mortality of patients with diabetes because of early detection of subclinical cardiovascular disease and active monitoring of the effectiveness of therapy. Surrogate markers of subclinical disease include conventional and contrast-enhanced ultrasound imaging of carotid artery intima-media thickness (c-IMT), 2-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle-brachial indices, and brachial artery reactivity testing. Because these noninvasive imaging tools are relatively comfortable and entail relatively low risk to the patient, they are ideal for initial screening and for the repeated imaging that is required for monitoring the effectiveness of therapy. Moreover, when used in large numbers of patients with diabetes, prediabetes, and the MS, these imaging tools may be useful in developing and validating thresholds for the use of lipid-lowering therapy as well as clear therapeutic goals for this population. In addition, contrast-enhanced c-IMT scans now produce real-time images of the vasa vasorum and neovascularization of atherosclerotic plaque, potentially causing a paradigm shift in our view of the genesis of atherosclerosis and affecting treatment options for all populations. Thus, surrogate markers may not only help improve individual patient outcomes, they also may help direct scarce medical resources to maximize medical benefits, improve overall medical care, and minimize costs and untoward side effects.

Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition.

OBJECTIVE: To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women. DESIGN: A community-based survey of women's health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Women's Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks. RESULTS: Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping. CONCLUSIONS: These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.

Change in quality of life from before to after discharge following left ventricular assist device implantation.

BACKGROUND: Quality of life (QOL) outcomes after left ventricular assist device (LVAD) implantation from before to after hospital discharge have been examined only in a very small sample of patients. The purposes of this study are to describe change in QOL from before to after hospital discharge in LVAD patients and to determine whether being discharged with an LVAD predicts better QOL than being hospitalized with an LVAD. METHODS: A non-random sample of 62 LVAD patients (approximately 50 years old, male, white, married, fairly well-educated) completed self-report questionnaires at >or=2 timepoints post-implant. The questionnaires (Quality of Life Index, Rating Question Form, Heart Failure Symptom Checklist, Sickness Impact Profile, LVAD Stressor Scale, Jalowiec Coping Scale), which were collated into booklets, had acceptable reliability and validity. Longitudinal analyses were performed in 2 steps using 1-sample t-tests and linear mixed effects modeling. RESULTS: Perception of QOL and health status were fairly good both before and after discharge of LVAD patients. Discharge predicted increased satisfaction with socioeconomic areas of life; decreased overall and psychologic stress and stress related to family and friends, self-care and work/school/finances; and decreased physical and self-care disability. CONCLUSIONS: QOL outcomes improved from before to after hospital discharge in LVAD patients awaiting heart transplantation. As LVADs potentially become available as destination therapy, in addition to being successful bridges to heart transplantation, QOL outcomes will become more important to study.

Change in quality of life from after left ventricular assist device implantation to after heart transplantation.

BACKGROUND: No studies have analyzed quality of life (QOL) from before to after heart transplantation in patients with a left ventricular assist device (LVAD). Therefore, the purpose of this longitudinal, multi-site study was to compare QOL outcomes of patients listed for heart transplantation who required a left ventricular assist device (LVAD) at 3 months after implantation of an LVAD vs 3 months after heart transplantation. METHODS: A non-random sample of 40 patients (predominantly middle-aged, married, white men), who had paired data at both 3 months after LVAD implantation and 3 months after heart transplantation, were investigated. Patients completed self-report questionnaires (with acceptable reliability and validity) at both time periods, including the Quality of Life Index, Rating Question Form, Heart Failure Symptom Checklist, Sickness Impact Profile, LVAD Stressor Scale (completed only after LVAD implant), Heart Transplant Stressor Scale (completed only after heart transplant) and Jalowiec Coping Scale. Descriptive analyses and comparative analyses using paired t-tests were performed with statistical significance set at 0.01. RESULTS: Patients were significantly more satisfied with their lives overall and with their health and functioning at 3 months after heart transplantation as compared with 3 months after LVAD implantation. Mobility, self-care ability, physical ability and overall functional ability improved from 3 months after LVAD implant to 3 months after heart transplant. There was significantly less symptom distress after LVAD implant as compared with after heart transplant for the neurologic, dermatologic and physical sub-scales. Work/school/financial stress was significantly lower after heart transplant vs after LVAD implant. In contrast, 2 other areas of stress were significantly lower after LVAD implant vs after heart transplant: self-care stress and hospital/clinic-related stress. CONCLUSIONS: Differences were found in QOL outcomes at 3 months after LVAD implant as compared with 3 months after heart transplant. Our findings point out specific areas of concern with respect to QOL after LVAD implant and post-transplant, some of which are amenable to health-care provider interventions.

Epidemiology and outcome of Clostridium difficile infection and diarrhea in HIV infected inpatients.

Clostridium difficile causes diarrhea in HIV infected patients but reports of prevalence, risk factors, and outcome vary. We studied the impact of C. difficile in 161 HIV infected inpatients admitted to Cook County Hospital. Patients with C. difficile had more hospital admissions in the previous 6 months (p =.04), spent more days in the hospital in the previous 3 months (p =.02), more often had previously received H2 blockers or treatment for Pneumocystis carinii (p <.05), and had a more frequent history of herpesvirus (p =.03) or opportunistic infections (p =.04). C. difficile associated diarrhea (CDAD) was the etiology in 32% of all study patients with diarrhea. Patients with CDAD were hospitalized for longer periods (p =.02) and received more antibiotics (p =.002). C. difficile was frequently present in our HIV infected patients, especially those with advanced HIV disease, but appeared to have little impact on morbidity or mortality.

Longitudinal change in quality of life and impact on survival after left ventricular assist device implantation.

BACKGROUND: The HeartMate vented electric left ventricular assist device has been approved for use as destination therapy. Thus, the study of quality-of-life outcomes, as well as morbidity and mortality, is imperative. The purpose of our study was to describe change with time (from 1 month to 1 year) in patients who received a HeartMate vented electric left ventricular assist device as a bridge to heart transplantation and to identify quality-of-life predictors of survival after left ventricular assist device implantation. METHODS: A nonrandom sample of 78 patients who received a HeartMate vented electric left ventricular assist device (primarily middle-aged, white married males) who had quality-of-life data at 1, 2, 3, 6, 9, or 12 months after implant was the subject of this report. The sample size decreased with time primarily because of heart transplantation. Patients completed the following booklets of questionnaires: Quality of Life Index, Rating Question Form, Heart Failure Symptom Checklist, and Sickness Impact Profile. Analyses included both descriptive analyses and modeling procedures (mixed-effects models and Cox proportional hazards models). RESULTS: Quality-of-life outcomes were fairly good and stable from 1 month to 1 year after HeartMate vented electric left ventricular assist device implantation. Both positive and negative changes were detected in all quality-of-life domains (physical and occupational function, social interaction, somatic sensation, and psychological state) after left ventricular assist device insertion. Items from the physical domain of quality of life, specifically walking and dressing oneself, were significantly associated with the risk of dying after left ventricular assist device implantation. CONCLUSIONS: Identifying poor quality-of-life outcomes within 1 year after left ventricular assist device implantation provides direction to develop strategies to improve outcomes. Physical and occupational rehabilitation, psychosocial intervention, and monitoring symptom distress and physical disability may contribute to improved quality-of-life outcomes and survival after left ventricular assist device implantation.

Comparison of echocardiography using tissue harmonics and contrast harmonics with radionuclide angiography for the assessment of left ventricular function.

BACKGROUND: Left ventricular ejection fraction (LVEF) is a significant predictor of morbidity and mortality; however, the optimal noninvasive modality for the quantitative determination of LVEF is not apparent. HYPOTHESIS: We verified the hypothesis that the various echocardiographic methods of assessing LVEF using the Method of Discs with contrast (Optison human albumin microspheres; Amersham Health, Princeton, NJ) and visual assessment of LVEF using tissue harmonics and contrast harmonics compare favorably with radionuclide angiography (RNA). METHODS: In a prospective analysis, 24 consecutive patients scheduled to undergo RNA had an echocardiogram using tissue harmonics and contrast harmonics on the same day. LVEF was assessed by RNA by an experienced, blinded reader using manual determination of the region of interest. LVEF was calculated using the Method of Discs (Simpson's Rule) by a blinded sonographer. LVEF was visually estimated by two blinded readers using echocardiography with tissue harmonics and contrast harmonics on separate occasions. RESULTS: By linear regression analysis, LVEF determination by echocardiography with contrast using the Method of Discs correlated well with RNA (r = .835, p < .0005). Using Bland-Altman analysis, the second echocardiogram reader had excellent agreement with RNA, whereas the first reader had a mean difference of 5.25% (CI 1.3-9.2; p = .012) with visual assessment using tissue harmonics and a mean difference of 4.67% (CI 0.4-8.8; p = .031) with visual assessment using contrast harmonics compared with RNA. Thus, a small difference in agreement between RNA and echocardiographic visual estimation was noted that appeared to be primarily reader dependent. CONCLUSIONS: LVEF determination with echocardiography with contrast using the Method of Discs correlated well with RNA and provided agreement across a range of cardiac functions. Visual echocardiographic assessment of LVEF with both tissue harmonics and contrast harmonics correlated well with RNA, but contrast harmonics did not appear to offer an advantage over tissue harmonics alone.

Improved in-hospital outcomes in acute coronary syndromes (unstable angina/non-ST segment elevation myocardial infarction) despite similar TIMI risk scores.

BACKGROUND: The Thrombolysis In Myocardial Infarction (TIMI) Risk Score has been shown to predict prognosis in acute coronary syndromes (ACS) comprised of unstable angina (UA) and non-ST segment elevation myocardial infarction (STEMI). We sought to evaluate the impact of newer antiplatelet and antithrombotic therapies for ACS, such as glycoprotein IIb/IIIa inhibitors (GPI) and low molecular weight heparin (LMWH), on in-hospital outcomes over time in patients (pts) with similar TIMI risk scores. METHODS: The baseline demographics and clinical outcomes of pts with ACS (UA and non-STEMI) in 1998 (Group 1998) and 2000 (Group 2000) at a single large university medical center were compared using a prospectively collected database. In-hospital major adverse cardiac events (MACE) included death, MI, or recurrent angina that resulted in urgent revascularization. Risk was estimated by utilizing the TIMI Risk Score, which uses 7 predictor variables: age > 65 years, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50%, ST segment deviation on EKG, severe angina, prior aspirin use, and elevated cardiac biomarkers. RESULTS: Comparing Group 1998 (n = 563) and Group 2000 (n = 604), there was no difference between the mean TIMI Risk Score (2.90 1.52 vs. 2.91 1.52; p = 0.97), demonstrating a similar risk profile. Nevertheless, significant improvement in in-hospital MACE (9.1% vs. 2.8%; p < 0.001) was noted. The improvement in MACE was due to differences in rates of recurrent angina, without significant differences in death and myocardial infarction. This occurred temporally in association with a significant increase in GPI (1.0% vs. 8.3%; p < 0.01) and LMWH (0.0% vs. 15.6%; p < 0.001) use within 24 hours of presentation, and the increased utilization of intracoronary stenting (46.6% vs. 64.6%; p = 0.005), findings which were confirmed with multivariate analysis. CONCLUSION: Despite similar TIMI Risk Scores, the in-hospital outcomes of pts with ACS have improved over time. This temporal change is associated with the greater use of newer antiplatelet and antithrombotic therapies and increased utilization of intracoronary stenting.

Safe and simple emergency department discharge therapy for patients with type 2 diabetes mellitus and severe hyperglycemia.

OBJECTIVE: To investigate the safety and effectiveness of 2 simple discharge regimens for use in patients with type 2 diabetes mellitus (DM2) and severe hyperglycemia, who present to the emergency department (ED) and do not need to be admitted. METHODS: We conducted an 8-week, open-label, randomized controlled trial in 77 adult patients with DM2 and blood glucose levels of 300 to 700 mg/dL seen in a public hospital ED. Patients were randomly assigned to receive glipizide XL, 10 mg orally daily (G group), versus glipizide XL, 10 mg orally daily, plus insulin glargine, 10 U daily (G+G group). The primary outcome was to maintain safe fasting glucose and random glucose levels of <350 and <500 mg/dL up to 4 weeks and <300 and <400 mg/dL, respectively, thereafter and to have no return ED visits (responders). RESULTS: Baseline characteristics were similar between the 2 treatment groups. The primary outcome was achieved in 87% of patients in both treatment groups. The enrollment mean blood glucose values of 440 and 467 mg/dL in the G and G+G groups, respectively, declined by the end of week 1 to 298 and 289 mg/dL and by week 8 to 140 and 135 mg/dL, respectively. Homeostasis model assessment of beta-cell function and early insulin response improved 7-fold and 4-fold, respectively, in responders at the end of the 8-week study. CONCLUSION: Sulfonylurea with and without use of a small dose of insulin glargine rapidly improved blood glucose levels and beta-cell function in patients with DM2. Use of sulfonylurea alone once daily can be considered a safe discharge regimen for such patients and an effective bridge between ED intervention and subsequent follow-up.

Individual assessment of arteriosclerosis by empiric clinical profiling.

BACKGROUND: Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient. METHODOLOGY/PRINCIPAL FINDINGS: 269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient's disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125). CONCLUSIONS/SIGNIFICANCE: Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis.

Characterizing daily urinary hormone profiles for women at midlife using functional data analysis.

The availability of daily hormone values for entire menstrual cycles offers an opportunity to apply new analytic techniques that confirm current knowledge and provide new insights into patterns of changing hormone profiles in women as they transition to the menopause. The Study of Women's Health Across the Nation (SWAN) collected urine samples during 1997-1999 from one menstrual cycle or up to 50 days from 848 women who live in seven cities across the United States. These samples were assayed for the urinary forms of estrogen, progesterone, follicle-stimulating hormone, and luteinizing hormone. The authors used functional data analysis to study variability in the hormone patterns of 572 of the 848 pre- and early-perimenopausal women with evidence of a luteal transition. Functional data analysis enabled the authors to identify asymmetries in women's hormone patterns related to cycle length that are not captured with single hormone value comparisons. Longer cycles were characterized by increasing dyssynchrony between follicle-stimulating hormone and luteinizing hormone in the luteal phase.

Cognitive functioning and sex steroid hormone gene polymorphisms in women at midlife.

Single nucleotide polymorphism (SNP) genotype frequencies were examined to determine whether variation in 6 estrogen-related genes was associated with differences in cognitive functioning in women at midlife. DNA from a multiracial/multiethnic sample of 875 African American, Caucasian, Chinese, and Japanese women aged 45 to 56 years participating in the Study of Women's Health Across the Nation (SWAN) was genotyped. Gene markers from the sex steroid hormone pathway were linked to measures of cognitive functioning including the Digit Span Backward Test (DSB), a measure of working memory; the Symbol Digit Modalities Test (SDMT), a measure of perceptual speed; and the East Boston Memory Test (EBMT), a measure of episodic memory. Statistical models were fit using logistic regression and general linear models to estimate the strength of association of estrogen-related polymorphisms with DSB, SDMT, and EBMT scores. On the EBMT, African American women and Caucasian women with ESR1 rs9340799 GG genotypes had about 1.5 to 2.0 times greater odds of remembering story elements on the EBMT-immediate recall test. Caucasian women with ESR1 rs2234693 CC genotypes had 1.3 to 1.5 times greater odds of remembering story elements on the EBMT-delayed recall test. Chinese women with 17HSD rs615942 GG genotypes, 17HSD rs592389 TT genotypes, and 17HSD rs2830 GG genotypes had about 1.7 times greater odds of remembering story elements on the EBMT-immediate recall test. African American women with CYP 19 rs936306 CC genotypes had about 0.25 to 0.40 lower odds of remembering story elements on the EBMT-immediate recall test, whereas Chinese women with CYP 19 rs936306 CC genotypes had about 2.3 times greater odds of remembering story elements on both the EBMT-immediate and -delayed recall tests. On the DSB, African American women with CYP 19 rs749292 GG genotype had a higher mean score. On the SDMT, Japanese women with ESR1 rs728524 GG genotypes had a higher mean score. On the 3 tests of cognitive functioning, there was 1 significant finding for CYP1A1 and none for the CYP1B1 or ESR2 SNPs. We conclude that selected genes involved in estrogen synthesis and metabolism may be associated with performance differences on cognitive function tests. Also, the relevant estrogen-related polymorphisms may vary by race/ethnicity.

Computer expert systems for African-American smokers in physicians offices: a feasibility study.

BACKGROUND: Stage-based computer expert systems (CES), delivered in physician offices, may offer unique opportunities to combine high participation and high efficacy, resulting in a high public health impact. Applying this technology in settings serving low-income African-American smokers, with the addition of practical tools for stress reduction, may help to reduce disparities in morbidity and mortality from smoking-related diseases. METHODS: Ninety-eight African-American smokers were recruited from a publicly funded, continuity care clinic waiting room to a study of computer interactive feedback and stress reduction audiotapes. The study was designed to assess: participation and retention rates; acceptability of both the computer expert system and the audiotapes; the fit of the transtheoretical model for the target population; and the 6-month shift in stages of change. RESULTS: Overall, 55.6% of invited smokers participated, 75.5% were seen at all three observation points. The CES and the audiotape were rated as highly interesting, relevant, and new, and most participants tried them. The predictable relationship between stage and decisional balance was reproduced in this low income African-American population. Significant stage progression occurred from baseline to 3 months (P = 0.011), from 3 to 6 months (P = 0.0001), and from baseline to 6 months (P = 0.0001). CONCLUSIONS: These data support the feasibility, acceptability and potential efficacy of stage-tailored computer interactive feedback plus stress reduction intervention delivered at the point of service to low-income African-Americans.