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1.  Reproducibility of Arterial Elasticity Parameters Derived from Radial Artery Diastolic Pulse Contour Analysis: The Multi-Ethnic Study of Atherosclerosis 
Blood pressure monitoring  2010;15(6):312-315.
The aim of this report was to describe the reproducibility of arterial elasticity parameters derived from radial artery diastolic pulse contour analysis.
Two measurements were performed on the same day by the same technician with the HDI/Pulsewave CR-2000 (Eagan, MN) on each of a subset of participants selected at random from the Multi-Ethnic Study of Atherosclerosis (MESA). Large and small artery elasticity (C1 and C2), C1 and C2 each multiplied by systemic vascular resistance (C1xR and C2xR, which are functions of the radial artery pulse waveform only), and systolic and diastolic blood pressure (SBP and DBP) were evaluated.
Two measurements were performed on each of 131 participants. The mean difference ± standard deviation of the difference was −0.13 ± 3.5 mmHgx10 for C1, −0.03 ± 1.5 mmHg ×100 for C2, 0.10 ± 4.6 seconds ×10 for C1xR, 0.05 ± 1.8 seconds ×100 for C2xR, 2.8 ± 8.2 mmHg for SBP, and 1.5 ± 5.0 mmHg for DBP. The between-measure correlation was 0.74 for C1, 0.84 for C2, 0.58 for C1xR, 0.74 for C2xR, 0.90 for SBP, and 0.86 for DBP.
The reproducibility of arterial elasticity measurements is less than that of systolic and diastolic blood pressure. Multiple measurements of arterial elasticity from a participant are recommended.
PMCID: PMC4028156  PMID: 20890179
arterial elasticity; arterial compliance; reproducibility; blood pressure measurement
2.  Association of Small Artery Elasticity With Incident Cardiovascular Disease in Older Adults 
American Journal of Epidemiology  2011;174(5):528-536.
Functional biomarkers like large artery elasticity (LAE) and small artery elasticity (SAE) may predict cardiovascular disease (CVD) events beyond blood pressure. The authors examined the prognostic value of LAE and SAE for clinical CVD events among 6,235 Multi-Ethnic Study of Atherosclerosis participants who were initially aged 45–84 years and without symptomatic CVD. LAE and SAE were derived from diastolic pulse contour analysis. During a median 5.8 years of follow-up between 2000 and 2008, 454 adjudicated CVD events occurred, including 256 cases of coronary heart disease (CHD), 93 strokes, and 126 heart failures (multiple diagnoses were possible). After adjustment for age, race/ethnicity, sex, clinic, height, heart rate, body mass index, systolic and diastolic blood pressure, use of antihypertensive and cholesterol-lowering medications, smoking, total cholesterol, high density lipoprotein cholesterol, triglycerides, diabetes, and high-sensitivity C-reactive protein, the hazard ratio for any CVD per standard-deviation increase in SAE was 0.71 (95% confidence interval: 0.61, 0.83; P < 0.0001). The lowest (stiffest) SAE quartile had a hazard ratio of 2.28 (95% confidence interval: 1.55, 3.36) versus the highest (most elastic) quartile. The net reclassification index, conditional on base risk, was 0.11. SAE was significantly associated with future CHD, stroke, and heart failure. After adjustment, LAE was not significantly related to CVD. In asymptomatic participants free of overt CVD, lower SAE added prognostic information for CVD, CHD, stroke, and heart failure events.
PMCID: PMC3202150  PMID: 21709134
arteries; cardiovascular diseases; elasticity; risk factors
3.  Body size adjustments for left ventricular mass by cardiovascular magnetic resonance and their impact on left ventricular hypertrophy classification 
Methods to index left ventricular (LV) mass, measured by cardiovascular magnetic resonance (CMR), for body size have not been investigated. The purposes of this study were to develop allometric indices for LV mass measured by CMR and compare estimates of the prevalence and predictive value of LV hypertrophy defined by a new allometric height-weight index, LV mass/body surface area (BSA), height indices (a new allometric height index; and previously derived indices from echocardiographic measurements: LV mass/height2, LV mass/height2.7), and non-indexed LV mass. 5,004 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with CMR measurements of LV mass and no clinical cardiovascular disease at baseline were followed for a median of 4.1 years. The new indices and limits for hypertrophy (95th percentile) were derived from 822 normal-weight, normotensive, non-diabetic MESA participants. 107 events (coronary heart disease or stroke) were observed. The estimated prevalence of hypertrophy at baseline and hazard ratio for event associated with hypertrophy were 8% and 2.4 with the new allometric height-weight index, 11% and 2.2 with LV mass/BSA, 23–24% and 2.0–2.1 with height indices, and 20% and 1.7 with non-indexed LV mass. A statistically significant difference was detected between the hazard ratios based on the new height-weight index and non-indexed LV mass. The prevalence of hypertrophy is higher for indices that do not account for weight. The predictive value of hypertrophy is significantly better with the new allometric height-weight index than with non-indexed LV mass and may be better than indices without weight.
PMCID: PMC3037862  PMID: 20107905
Cardiovascular risk; Hypertension; Hypertrophy; LV mass index; Magnetic resonance imaging; Obesity
4.  Lack of Fit in Self Modeling Regression: Application to Pulse Waveforms* 
Self modeling regression (SEMOR) is an approach for modeling sets of observed curves that have a common shape (or sequence of features) but have variability in the amplitude (y-axis) and/or timing (x-axis) of the features across curves. SEMOR assumes the x and y axes for each observed curve can be separately transformed in a parametric manner so that the features across curves are aligned with the common shape, usually represented by non-parametric function. We show that when the common shape is modeled with a regression spline and the transformational parameters are modeled as random with the traditional distribution (normal with mean zero), the SEMOR model may surprisingly suffer from lack of fit and the variance components may be over-estimated. A random effects distribution that restricts the predicted random transformational parameters to have mean zero or the inclusion of a fixed transformational parameter improves estimation. Our work is motivated by arterial pulse pressure waveform data where one of the variance components is a novel measure of short-term variability in blood pressure.
PMCID: PMC2836211  PMID: 20305704
functional data; nonlinear mixed effects models; self-modeling
5.  Endpoints for Clinical Trials in Young Children with Cystic Fibrosis 
The availability of sensitive, reproducible, and feasible outcome measures for quantifying lung disease in children with cystic fibrosis (CF) younger than 6 years is critical to the conduct of clinical trials in this important population. Historically, identifying and quantifying the presence of lung disease in very young children with CF was hampered by a lack of reproducible measures of lung function or lung pathology. Over the past 10 years, significant progress has led to physiologic, anatomic, and bronchoscopic measures that may serve as endpoints for future intervention trials. These endpoints include infant and preschool lung function testing, computed tomography of the chest, and bronchoalveolar lavage markers of inflammation and infection. Much progress has occurred in standardizing lung function testing, which is essential for multicenter collaboration. Pulmonary exacerbation has the potential to serve as a clinical endpoint; however, there is currently no standardized definition in children with CF younger than 6 years. Further development of these outcomes measures will enable clinical trials in the youngest CF population with the objective of improving long-term prognosis.
PMCID: PMC2647606  PMID: 17652509
infant; child, preschool; respiratory function tests, computed tomography scanners, X-ray; bronchoalveolar lavage
6.  Methadone Medical Maintenance in Primary Care 
Methadone is effective treatment for opioid addiction, but regulations restrict its use. Methadone medical maintenance treats stabilized methadone patients in a medical setting, but only experimental programs have been studied.
To evaluate the implementation of the first methadone medical maintenance program established outside a reseach setting.
One-year program evaluation.
A public hospital and a community opioid treatment program.
Methadone patients with >1 year of clinical stability. Eleven generalist physicians and 4 hospital pharmacists.
Regulatory exemptions were requested. Physicians and pharmacists were trained. Patients were transferred to the medical setting and permitted 1-month supplies of methadone.
Patient eligibility and willingness to enroll, treatment retention, urine toxicology results, change in addiction severity and functional status, medical services provided, patient and physician satisfaction, and physician attitudes toward methadone maintenance.
Regulatory exemptions were obtained after a 14-month process, and the program was cited in federal policy as acceptable for widespread implementation. Forty-nine of 684 patients (7.2%) met stability criteria, and 30 enrolled. Twenty-eight were retained for 1 year, and 2 transferred to other programs. Two patients had opioid-positive urine tests and were managed in the medical setting. Previously unmet medical needs were addressed, and the Addiction Severity Index (ASI) medical composite score improved over time (P =.02). Patient and physician satisfaction were high, and physician attitudes toward methadone maintenance treatment became more positive (P =.007).
Methadone medical maintenance is complex to arrange but feasible outside a research setting, and can result in good clinical outcomes.
PMCID: PMC1490098  PMID: 15857492
methadone; heroin addiction; opioid-related disorders; outcome and process assessment

Results 1-6 (6)