George Divine

Peak aerobic capacity predicts prognosis in patients with coronary heart disease

BACKGROUND It is unknown if contemporary preventive treatments such as statins or primary percutaneous coronary intervention in patients with coronary heart disease (CHD) have rendered obsolete the use of measured exercise capacity for assessment of future risk and prognosis. Using a sample of patients from 2 clinical sites, most of whom were taking beta-blockade, antiplatelet, and statin therapy, we hypothesized that peak oxygen consumption (Vo(2)) would remain a strong and independent predictor of all-cause and cardiovascular-specific mortality in men and women with CHD. METHODS We studied 2,812 patients with CHD between 1996 and 2004. All-cause and cardiovascular disease-specific mortality served as end points. RESULTS In all men and women and in a subgroup of patients following evidence-based care, peak Vo(2) remained a strong predictor of all-cause death, with every 1 mL x kg(-1) x min(-1) increase in peak Vo(2) associated with an approximate 15% decrease in risk of death. Among men, a peak Vo(2) (mL x kg(-1) x min(-1)) below approximately 15 was associated with the highest risk, whereas a peak Vo(2) above approximately 19 was associated with a low rate and risk for annual all-cause mortality. Among women, a peak Vo(2) below approximately 12 was associated with the highest risk, whereas a peak Vo(2) above approximately 16.5 was associated with the lowest rate and risk for annual all-cause mortality. CONCLUSIONS In men and women with CHD, peak Vo(2) remains an independent predictor of all-cause and cardiovascular-specific mortality.

Thiazolidinedione Use and the Longitudinal Risk of Fractures in Patients with Type 2 Diabetes Mellitus

CONTEXT Thiazolidinedione (TZD) use has recently been associated with an increased risk of fractures. OBJECTIVE The aim of this study was to determine the time-dependent relationship between TZD use and fracture risk. DESIGN We conducted a retrospective cohort study in a large health system in southeast Michigan. PATIENTS PATIENTS who received care from the health system were included if they were at least 18 yr of age, had a diagnosis of diabetes, and had at least one prescription for an oral diabetes medication. These criteria identified 19,070 individuals (9,620 women and 9,450 men). INTERVENTION This study compared patients treated with TZDs to patients without TZD treatment. Cox proportional hazard models were used to assess the relationship between exposure and outcomes. MAIN OUTCOME MEASURES The primary outcome was the time to fracture. Secondary analyses examined the risk of fractures in subgroups defined by sex and age. RESULTS TZD use was associated with an increased risk of fracture in the cohort overall [adjusted hazard ratio (aHR), 1.35; 95% confidence interval (CI), 1.05-1.71] and in women (aHR, 1.57; 95% CI, 1.16-2.14), but not in men (aHR, 1.05; 95% CI, 0.70-1.58). Women more than 65 yr of age appeared to be at greatest risk for fracture (aHR, 1.72; 95% CI, 1.17-2.52). Among women, the increased fracture risk was not apparent until after 1 yr of TZD treatment. CONCLUSIONS TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr. Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients.

Diffusion-, T2-, and Perfusion-Weighted Nuclear Magnetic Resonance Imaging of Middle Cerebral Artery Embolic Stroke and Recombinant Tissue Plasminogen Activator Intervention in the Rat

Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2 (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). Diffusion-weighted imaging, T2WI, and PWI were performed before, during, and after embolization from 1 hour to 7 days. After embolization in both rt-PA-treated and control animals, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) in the ischemic region significantly declined from the preischemic control values (P < 0.001). However, mean CBF and ADCw in the rt-PA—treated group was elevated early after administration of rt-PA compared with the untreated control group, and significant differences between the two groups were detected in CBF (24 hours after embolization, P < 0.05) and ADCw (3, 4, and 24 hours after embolization, P < 0.05). T2 values maximized at 24 (control group, P < 0.001) or 48 hours (treated group, P < 0.01) after embolization. The increase in T2 in the control group was significantly higher at 24 hours and 168 hours than in the rt-PA—treated group (P < 0.05). Significant correlations (r ≥ 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADCw obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADCw and T2 data maps, indicated a significant reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADCw obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the increase of T2, and a reduction of the ischemic lesion size measured using MRI cluster analysis.

A Randomized Clinical Trial Evaluating Online Interventions to Improve Fruit and Vegetable Consumption

OBJECTIVES We assessed change in fruit and vegetable intake in a population-based sample, comparing an online untailored program (arm 1) with a tailored behavioral intervention (arm 2) and with a tailored behavioral intervention plus motivational interviewing-based counseling via e-mail (arm 3). METHODS We conducted a randomized controlled intervention trial, enrolling members aged 21 to 65 years from 5 health plans in Seattle, Washington; Denver, Colorado; Minneapolis, Minnesota; Detroit, Michigan; and Atlanta, Georgia. Participants reported fruit and vegetable intake at baseline and at 3, 6, and 12 months. We assessed mean change in fruit and vegetable servings per day at 12 months after baseline, using a validated self-report fruit and vegetable food frequency questionnaire. RESULTS Of 2540 trial participants, 80% were followed up at 12 months. Overall baseline mean fruit and vegetable intake was 4.4 servings per day. Average servings increased by more than 2 servings across all study arms (P<.001), with the greatest increase (+2.8 servings) among participants of arm 3 (P=.05, compared with control). Overall program satisfaction was high. CONCLUSIONS This online nutritional intervention was well received, convenient, easy to disseminate, and associated with sustained dietary change. Such programs have promise as population-based dietary interventions.

T1 and magnetization transfer at 7 Tesla in acute ischemic infarct in the rat

T1 and magnetization transfer at a field strength of 7 Tesla were used to discriminate between water accumulation and protein mobilization in tissue undergoing infarction. Twelve rats subjected to acute stroke via intralumenal suture occlusion of the middle cerebral artery, and 19 controls, were studied. In MRI studies to 6 hr post‐ictus, serial data acquisition allowed the measurement of cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), equilibrium magnetization (M0) and T1, and equilibrium magnetization and T1 under an off‐resonance partial saturation of the macromolecular pool (Msat and T1sat). Using these parameters, the apparent forward transfer rate of magnetization between the free water proton pool and the macromolecular proton pool, kfa, was calculated. Regions of interest (ROIs) were chosen using depressed areas in maps of the ADCw. T1 measurements in bovine serum albumin at 7T were not affected by the mobility of the macromolecular pool (P > 0.2), but magnetization transfer between free water and protein depended strongly on the mobility of the macromolecular pool (P < 0.001). For 6 hr after ictus, kfa uniformly and strongly decreased in the region of the infarct (P < 0.0001). Ratios (ischemic/non‐ischemic) of parameters M0, Msat, T1, and T1sat all uniformly and strongly increased in the infarct. The ratio T1/T1sat in the region of infarction showed that a progressive accumulation of free water in the region of interest was the major (>80%) contribution to the decrease in kfa. There also existed a small contribution due to changes at the water‐macromolecular interface, possibly due to proteolysis (P = 0.005). Magn Reson Med 41:696–705, 1999.

Recruitment to a Randomized Web-Based Nutritional Intervention Trial: Characteristics of Participants Compared to Non-Participants

Background Web-based behavioral programs efficiently disseminate health information to a broad population, and online tailoring may increase their effectiveness. While the number of Internet-based behavioral interventions has grown in the last several years, additional information is needed to understand the characteristics of subjects who enroll in these interventions, relative to those subjects who are invited to enroll. Objective The aim of the study was to compare the characteristics of participants who enrolled in an online dietary intervention trial (MENU) with those who were invited but chose not to participate, in order to better understand how these groups differ. Methods The MENU trial was conducted among five health plans participating in the HMO Cancer Research Network in collaboration with the University of Michigan Center for Health Communication Research. Approximately 6000 health plan members per site, between the ages of 21 and 65, and stratified by gender with oversampling of minority populations, were randomly selected for recruitment and were mailed an invitation letter containing website information and a US

Direct Comparison of Local Cerebral Blood Flow Rates Measured by MRI Arterial Spin-Tagging and Quantitative Autoradiography in a Rat Model of Experimental Cerebral Ischemia

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Provider type and the receipt of general and diabetes-related preventive health services among patients with diabetes.

20 for completing follow-up surveys. Administrative and area-based data using geocoding along with baseline survey data were used to compare invitees (HMO members sent the introductory letter), responders (those who entered a study ID on the website), and enrollees (those who completed the enrollment process). Generalized estimating equation multivariate and logistic regression models were used to assess predictors of response and enrollment. Results Of 28,460 members invited to participate, 4270 (15.0%) accessed the website. Of the eligible responders, 2540 (8.9%) completed the consent form and baseline survey and were enrolled and randomized. The odds of responding were 10% lower for every decade of increased age (P < .001), while the likelihood of enrolling was 10% higher for every decade increase in age (P < .001). Women were more likely to respond and to enroll (P < .001). Those living in a census tract associated with higher education levels were more likely to respond and enroll, as well as those residing in tracts with higher income (P < .001). With a 22% (n = 566) enrollment rate for African Americans and 8% (n = 192) for Hispanics, the enrolled sample was more racially and ethnically diverse than the background sampling frame. Conclusions Relative to members invited to participate in the Internet-based intervention, those who enrolled were more likely to be older and live in census tracts associated with higher socioeconomic status. While oversampling of minority health plan members generated an enrolled sample that was more racially and ethnically diverse than the overall health plan population, additional research is needed to better understand methods that will expand the penetration of Internet interventions into more socioeconomically diverse populations. Trial Registration Clinicaltrials.gov NCT00169312; http://clinicaltrials.gov/ct2/show/NCT00169312 (Archived by WebCite at http://www.webcitation.org/5jB50xSfU)

Effect of incentives and mailing features on online health program enrollment.

The present study determined cerebral blood flow (CBF) in the rat using two different magnetic resonance imaging (MRI) arterial spin-tagging (AST) methods and 14C-iodoantipyrine (IAP)-quantitative autoradiography (QAR), a standard but terminal technique used for imaging and quantitating CBF, and compared the resulting data sets to assess the precision and accuracy of the different techniques. Two hours after cerebral ischemia was produced in eight rats via permanent occlusion of one middle cerebral artery (MCA) with an intraluminal suture, MRI-CBF was measured over a 2.0-mm coronal slice using single-coil AST, and tissue magnetization was assessed by either a spin-echo (SE) or a variable tip-angle gradient-echo (VTA-GE) readout. Subsequently (∼2.5 hours after MCA occlusion), CBF was assayed by QAR with the blood flow indicator 14C-IAP, which produced coronal images of local flow rates every 0.4 mm along the rostral—caudal axis. The IAP-QAR images that spanned the 2-mm MRI slice were selected, and regional flow rates (i.e., local CBF [lCBF]) were measured and averaged across this set of images by both the traditional approach, which involved reader interaction and avoidance of sectioning artifacts, and a whole film-scanning technique, which approximated total radioactivity in the entire MRI slice with minimal user bias. After alignment and coregistration, the concordance of the CBF rates generated by the two QAR approaches and the two AST methods was examined for nine regions of interest in each hemisphere. The QAR-lCBF rates were higher with the traditional method of assaying tissue radioactivity than with the MRI-analog approach; although the two sets of rates were highly correlated, the scatter was broad. The flow rates obtained with the whole film-scanning technique were chosen for subsequent comparisons to MRI-CBF results because of the similarity in tissue “sampling” among these three methods. As predicted by previous modeling, “true” flow rates, assumed to be given by QAR-lCBF, tended to be slightly lower than those measured by SE and were appreciably lower than those assessed by VTA-GE. When both the ischemic and contralateral hemispheres were considered together, SE-CBF and VTA-GE-CBF were both highly correlated with QAR-lCBF (P < 0.001). If evaluated by flow range, however, SE-CBF estimates were more accurate in high-flow (contralateral) areas (CBF > 80 mL · 100 g−1 · min−1), whereas VTA-GE-CBF values were more accurate in low-flow (ipsilateral) areas (CBF ≤ 60 mL · 100 g−1 · min−1). Accordingly, the concurrent usage of both AST-MRI methods or the VTA-GE technique alone would be preferred for human studies of stroke.

Inconsistencies in patient perceptions and observer ratings of shared decision making: The case of colorectal cancer screening

Objective.Using a measure of provider type that includes “shared care” to determine the contribution of provider type on receipt of general and diabetes-related preventive health services. Methods.Automated clinical and administrative data were used to identify adult patients with type 1 and 2 diabetes receiving care from a multispecialty, salaried group practice and enrolled in a large health maintenance organization between 3/97 and 2/98 (n = 10,991). Logistic regression models were fit using generalized estimating equation approaches to evaluate the contribution of provider type on service receipt. Measures.Preventive service receipt included receipt of glycated hemoglobin and lipid testing, retinal examinations, pneumococcal vaccines, Papanicolaou (Pap) smears, and mammograms. Multivariable analyses adjusted for age, sex, race, marital status, household income, diabetes-related comorbidities and complications, prescription drug use, laboratory testing results, and frequency of medical care contact. Results.Patients seeing an endocrinologist and primary care physician (PCP) were more likely than those seeing endocrinologists alone to receive glycated hemoglobin testing (OR, 1.42), lipid testing (OR, 1.72), mammograms (OR, 2.12), and Pap smears (OR, 2.36), and more likely than those seeing PCPs alone to receive glycated hemoglobin testing (OR, 1.79), lipid testing (OR, 1.54), retinal examinations (OR, 1.33), and mammograms (OR, 1.43). Compared with patients seeing PCPs only, patient’s seeing endocrinologists only were more likely to receive retinal examinations (OR, 1.37) and less likely to receive Pap smears (OR, 0.46). Conclusions.Care delivered by no one single provider type is associated with greater receipt of all recommended services. Instead, patients seeing both an endocrinologist and a PCP are most likely to receive recommended services.