Cholesterol management: targeting a lower low-density lipoprotein cholesterol concentration increases adult treatment panel-III goal attainment.
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Adult↗
Biomedical subjects
Walter T Ambrosius
Publications and source records attributed to Walter T Ambrosius.
Exercise, self-efficacy, and mobility performance in overweight and obese older adults with knee osteoarthritis.
OBJECTIVE: To examine changes in mobility-related self efficacy following exercise and dietary weight loss interventions in overweight and obese older adults with knee osteoarthritis (OA), and to determine if self efficacy and pain mediate the effects of the interventions on mobility task performance. METHODS: The Arthritis, Diet, and Activity Promotion Trial was an 18-month, single-blind, randomized, controlled trial comparing the effects of exercise alone, dietary weight loss alone, a combination of exercise plus dietary weight loss, and a healthy lifestyle control intervention in the treatment of 316 overweight or obese older adults with symptomatic knee OA. Participants completed measures of stair-climb time and 6-minute walk distance, self efficacy for completing each mobility task, and self-reported pain at baseline, 6 months, and 18 months during the trial. RESULTS: Mixed model analyses of covariance of baseline adjusted change in the outcomes demonstrated that the exercise + dietary weight loss intervention produced greater improvements in mobility-related self efficacy (P = 0.0035), stair climb (P = 0.0249) and 6-minute walk performance (P = 0.00031), and pain (P = 0.09) when compared with the healthy lifestyle control intervention. Mediation analyses revealed that self efficacy and pain served as partial mediators of the beneficial effect of exercise + dietary weight loss on stair-climb time. CONCLUSION: Exercise + dietary weight loss results in improved mobility-related self efficacy; changes in these task-specific control beliefs and self-reported pain serve as independent partial mediators of the beneficial effect of exercise + dietary weight loss on stair-climb performance.
Activities of Daily Living↗
Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension.
Hypertension in blacks is more prevalent and less often controlled than the hypertension of other ethnic groups. We sought to explore the benefit of adding inhibitors of the epithelial sodium channel (ENaC), an aldosterone-regulated site of sodium reabsorption in the distal nephron, to the antihypertensive regimen of black hypertensive patients. In a prospective, randomized, placebo-controlled, double-blind clinical trial, we used a 2-by-2 factorial design with 4 treatment groups: amiloride (a direct inhibitor of ENaC), spironolactone (an aldosterone receptor antagonist), the combination of both drugs, and placebo. The subjects (n=98) had an elevated blood pressure despite treatment that included a diuretic and a calcium channel blocker; the level of plasma renin activity was < or =0.56 ng/L per second. The primary end points were changes from baseline in systolic and diastolic blood pressure over a 9-week period of treatment. The reductions in systolic and diastolic blood pressures (mm Hg) were, respectively, 9.8+/-1.6 (SE) and 3.4+/-1.0 for amiloride (P<0.001) and 4.6+/-1.6 (P=0.006) and 1.8+/-1.0 for spironolactone (P=0.07). Treatment with either amiloride or spironolactone or the combination was well tolerated; no patient experienced hyperkalemia. In a substudy, plasma endothelin-1 levels were observed to decrease after 3 weeks of treatment with spironolactone (P<0.001), consistent with a non-ENaC-related potential benefit of spironolactone. In conclusion, treatment with either amiloride or spironolactone can provide an additional reduction in blood pressure in blacks already receiving conventional antihypertensive therapy.
Amiloride↗
Enhancing quality of heart failure care in managed Medicare and Medicaid in North Carolina: results of the North Carolina Achieving Cardiac Excellence (NC ACE) Project.
OBJECTIVES: To evaluate an intervention to improve the quality of care of patients with heart failure in managed Medicare and Medicaid plans in North Carolina. BACKGROUND: Utilization of angiotensin-converting enzyme inhibitors (ACE-I) and beta-adrenergic receptor blockers (BB) in heart failure (HF) patients remains suboptimal despite evidence-based guidelines supporting their use. METHODS: Managed care plans identified adult patients with HF during 2000 (preintervention) and from July 1, 2001, through June 30, 2002 (postintervention). Outpatient medical records were reviewed to obtain data regarding type of heart failure, demographics, comorbidities, and therapies. The intervention consisted of guideline summary dissemination, performance audit with feedback, patient-specific chart reminders, and patient activation mailings. RESULTS: We sampled 1613 patients from 5 plans during the preintervention period and 1528 patients during the postintervention period. Assessment of left ventricular function (LVF) increased from 88.2% to 92.5% of patients (P < .0001). Among patients with moderate to severe left ventricular systolic dysfunction, there was no substantive change in treatment with ACE-I or vasodilators, whereas, appropriate treatment with BB increased from 48.3% (with another 11.9% with documented contraindications) to 67.9% (with another 7.5% with documented contraindications). The quality gap decreased from 39.8% to 24.6% (P < .0001). CONCLUSION: LVF assessment improved despite high preintervention rates. Treatment rates with ACE-I and vasodilators remained high, but did not improve. Treatment rates with BB improved substantially translating into a significant public health benefit. Health-care payers should consider development of financial incentives to encourage collaborative quality improvement programs.
Adrenergic beta-Antagonists↗
Sarcopenia, obesity, and inflammation--results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study.
BACKGROUND: Age-related body-composition changes are associated with health-related outcomes in elders. This relation may be explained by inflammation and hemostatic abnormalities. OBJECTIVES: Our objectives were to evaluate the relation between body-composition measures [body mass index (BMI), total fat mass, and appendicular lean mass (aLM)] and C-reactive protein (CRP), interleukin 6 (IL-6), and plasminogen activator inhibitor 1 (PAI-1) and to explore the effect of obesity and sarcopenia on CRP, IL-6, and PAI-1 concentrations. DESIGN: The data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study baseline visit (n = 286; mean age = 66.0 y). Total fat mass and aLM were assessed with a dual-energy X-ray absorptiometry scan. Linear regressions were performed between body-composition measures and CRP, IL-6, or PAI-1 concentrations. The effect of sarcopenia and obesity (defined as the percentage of fat mass) on CRP, IL-6, and PAI-1 concentrations was evaluated with the use of analyses of covariance. RESULTS: CRP and IL-6 were positively associated with both BMI [beta = 0.027 (P = 0.03) and beta = 0.048 (P < 0.001), respectively] and total fat mass [beta = 0.049 (P < 0.001) and beta = 0.055 (P < 0.001), respectively] and were inversely associated with fat-adjusted aLM [beta = -0.629 (P = 0.002) and beta = -0.467 (P = 0.02), respectively]. PAI-1 was positively associated with both BMI (beta = 0.038, P = 0.005) and total fat mass (beta = 0.032, P = 0.007). No significant interaction was found between either obesity or sarcopenia and CRP, IL-6, and PAI-1 concentrations. Obesity remained significantly associated with high CRP and IL-6 concentrations after adjustments for sarcopenia. CONCLUSIONS: CRP and IL-6 are positively associated with total fat mass and negatively associated with aLM. Obesity-associated inflammation may play an important role in the age-related process that leads to sarcopenia. The relation of inflammation with sarcopenia was not independent of any of the considered obesity indexes.
Aged↗
Dietary oxalate loads and renal oxalate handling.
PURPOSE: Dietary oxalate makes a significant contribution to urinary oxalate excretion and, thus, may have a role in calcium oxalate kidney stone formation. Studies have indicated that the ingestion of oxalate rich foods results in transient increases in plasma oxalate concentrations and urinary oxalate excretion. We examined changes in plasma and urinary oxalate following oral crystalline oxalate loading under controlled dietary conditions to further define the renal handling of oxalate by normal adults. MATERIALS AND METHODS: Six normal adult subjects consumed controlled diets of known oxalate content for 1 week before ingesting loads of 0, 2, 4 and 8 mmol of oxalate. Urinary and plasma changes were measured to assess renal oxalate handling. Urinary excretion of proximal tubule derived enzymes and isoprostanes was monitored to assess for renal injury and oxidative stress. RESULTS: Time and dose dependent changes in plasma oxalate, urinary oxalate and in the clearance ratio of oxalate-to-creatinine were observed. A significant correlation (r=0.43, p <0.001) between the oxalate-to-creatinine clearance ratio and plasma oxalate levels was identified. No changes in urinary markers of oxidative stress or renal injury were observed following the 8 mmol oxalate load. CONCLUSIONS: Oxalate is rapidly absorbed and cleared by the kidney by filtration and secretion following an oral oxalate load. Renal oxalate secretion has a significant role in the renal handling of an oral oxalate load. There is no evidence of acute renal injury or oxidative stress with oral oxalate loads in these experimental conditions.
Adult↗
Activity of 11beta-hydroxysteroid dehydrogenase type 2 in normotensive blacks and whites.
BACKGROUND: Salt-sensitive hypertension occurs more commonly in Blacks than in Whites. A decrease in activity of the enzyme 11betaHSD2 that results in overstimulation of the mineralocorticoid receptor by cortisol could contribute to greater retention of sodium in Blacks. We tested the hypothesis that less activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is present in Blacks than in Whites. METHODS: Eighty-nine subjects (42 Whites and 47 Blacks), ages 12 to 24 years were recruited from a young cohort that was followed longitudinally in a study of blood pressure regulation. For purposes of study, they were admitted to the General Clinical Research Center. Excretion of tetrahydrocortisol (THF), 5alpha-THF, and tetrahydrocortisone (THE) was measured in 12-hour overnight urine collections. In vivo 11betaHSD2 activity was estimated from the urinary (THF + 5alpha-THF)/THE) ratio. RESULTS: Blacks appeared to retain more sodium as evidenced by a lower level of 2-hour upright plasma aldosterone (P<.001) and marginally lower plasma renin activity (P=.06). The (THF + 5alpha-THF)/THE ratio in Blacks and Whites was similar: 0.91 +/- 0.41 (standard deviation), 0.86 +/- 0.52, 1.13 +/- 0.36, and 0.66 +/- 0.26, in White males, White females, Black males, and Black females, respectively; P=.35 for an overall effect of race. CONDUSION: 11betaHSD2 activity appears to be similar in Blacks and Whites and probably contributes minimally, if at all, to race differences in sodium retention.
11-beta-Hydroxysteroid Dehydrogenase Type 2↗
Cross calibration in longitudinal studies.
In a long-running longitudinal study using complex machinery to obtain measurements, it is sometimes necessary to replace the machine. This can result in lack of continuity in the measurements that can overwhelm any treatment effect or time trend. We propose a Bayesian procedure implemented using Markov chain Monte Carlo to calibrate the measurements on the old machine utilizing both person-specific and population information. The goal is to convert the previous measurements to values that can be treated as though they were made on the new machine. This methodology is applied to a bone mineral density study where the first densitometer uses gadolinium as the energy source (Lunar DP-3) and the second uses X-rays (Hologic QDR-1000W). Finally, simulation results are presented to show the superiority of the proposed method over existing methods of cross calibration.
Calibration↗
Quality of heart failure care in managed Medicare and Medicaid patients in North Carolina.
Use of angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic receptor blockers in patients with heart failure (HF) remains low despite the results of clinical trials and evidence-based guidelines that support their use. The quality of HF care in managed Medicare and Medicaid programs in North Carolina participating in a HF quality improvement program was assessed. Managed care plans identified adult patients with 1 inpatient or 3 outpatient claims for HF during 2000. A stratified random sample of 971 Medicare and 642 Medicaid patients' outpatient medical records from 5 plans were reviewed by trained nurse abstractors to obtain data regarding type of HF, demographics, comorbidities, and therapies. Left ventricular function assessment was performed in 88% of patients. Among 494 patients with systolic dysfunction, 86% were appropriately treated with respect to ACE inhibitors (73% prescribed, 13% had a documented contraindication). In contrast, beta-blocker therapy was appropriate in 61% (49% prescribed, 12% contraindication). There were no significant differences in drug use by insurance, gender, race, or age. Ventricular function assessment and ACE inhibitor prescription rates are higher than beta-blocker prescription rates among Medicare and Medicaid managed care patients in North Carolina. Opportunities for improvement remain, particularly for beta-blocker use.
Adrenergic beta-Antagonists↗
Power for genetic association studies with random allele frequencies and genotype distributions.
One of the first and most important steps in planning a genetic association study is the accurate estimation of the statistical power under a proposed study design and sample size. In association studies for candidate genes or in fine-mapping applications, allele and genotype frequencies are often assumed to be known when, in fact, they are unknown (i.e., random variables from some distribution). For example, if we consider a diallelic marker with allele frequencies of 0.5 and 0.5 and Hardy-Weinberg proportions, the three genotype frequencies are often assumed to be 0.25, 0.50, and 0.25, and the statistical power is calculated. Unfortunately, ignoring this source of variation can inflate the estimated power of the study. In the present article, we propose averaging the estimates of power over the distribution of the genotype frequencies to calculate the true estimate of power for a fixed allele frequency. For the usual situation, in which allele frequencies in a population are not known, we propose placing a prior distribution on the allele frequency, taking advantage of any available genotype information. This Bayesian approach provides a more accurate estimate of power. We present examples for quantitative and qualitative traits in cohort studies of unrelated individuals and results from an extensive series of examples that show that ignoring the uncertainty in allele frequencies can inflate the estimated power of the study. We also present the results from case-control studies and show that standard methods may also overestimate power. As discussed in this article, the approach of fixing allele frequencies even if they are not known is the common approach to power calculations. We show that ignoring the sources of variation in allele frequencies tends to result in overestimates of power and, consequently, in studies that are underpowered. Software in C is available at http://www.ambrosius.net/Power/.
Alleles↗
Angiotensin-converting enzyme inhibition, body composition, and physical performance in aged rats.
This study was designed to test the effects of angiotensin-converting enzyme (ACE) inhibition on body composition and physical performance in aged rats. Male Brown Norway x F344 rats were randomized to receive daily injections of enalapril (40 mg/kg or 80 mg/kg) or saline from 24 to 30 months of age. Body composition was determined using dual-energy X-ray absorptiometry (DXA), and physical performance was assessed using the grip strength and inclined plane procedures. Performance measures were assessed at baseline and monthly thereafter. DXA was performed at baseline, 3 months, and 6 months of follow-up. Compared with the enalapril groups, the saline group experienced a greater 6-month decline in the physical performance measures. Lean body mass declined in both groups; however, the enalapril groups also experienced a significant loss of fat mass. These results suggest that ACE inhibition may prevent age-related declines in physical performance, which may be mediated by a reduction in body fat mass.
Age Factors↗
Group-mediated activity counseling and traditional exercise therapy programs: effects on health-related quality of life among older adults in cardiac rehabilitation.
BACKGROUND: Regular physical activity has been consistently related to improvements in health- related quality of life (HRQL) in older adults. Nevertheless, systematic investigations of the influence of exercise therapy on older men and women enrolled in cardiac rehabilitation remain sparse. PURPOSE: The primary purpose of this investigation was to compare the effects of a group-mediated cognitive behavioral physical activity intervention program (GMCB) to a traditional cardiac rehabilitation program (CRP) with regard to changes in HRQL in a community-dwelling sample of older adults. METHODS: This randomized clinical trial assigned 147 participants who were eligible for inclusion in cardiac rehabilitation to the GMCB or traditional CRP arms. Changes in HRQL at 3 and 12 months were assessed using the Short Form-36 (SF-36) from the Medical Outcomes Study. RESULTS: Mixed-model analyses yielded significant Baseline x Gender x Treatment interactions for the self-reported mental health component and the Vitality subscale of the SF-36. Decomposition of these interactions revealed that men in both exercise therapy groups and women in the GMCB treatment with low baseline values demonstrated more favorable improvements in the HRQL perceived mental health measures than women in the CRP treatment. CONCLUSIONS: Improvements in HRQL among older adults enrolled in cardiac rehabilitation differ as a function of treatment, gender, and initial mental health status. Results are discussed in terms of the implications for the design of future physical activity interventions among older adults with cardiovascular disease and the measurement of their HRQL.
Aged↗
The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity.
BACKGROUND: The relative susceptibility of intestinal and hepatic cytochrome P450 (CYP) 3A to induction by rifampin (INN, rifampicin), as a function of age and sex, was investigated with the CYP3A substrate midazolam. METHODS: Fourteen young women (mean age, 26 +/- 4 years), 14 young men (mean age, 27 +/- 4 years), 14 elderly women (mean age, 72 +/- 5 years), and 10 elderly men (mean age, 70 +/- 4 years) received simultaneous intravenous doses (0.05 mg/kg over a 30-minute period) and oral doses of midazolam (3-8 mg of a stable isotope, (15)N(3)-midazolam) before and after 7 days of rifampin dosing (600 mg once daily in the evening). Serum and urine samples were assayed for midazolam, (15)N(3)-midazolam, and metabolites by liquid chromatography-mass spectrometry. RESULTS: No significant difference (P > or =.05) in the baseline systemic and oral clearance of midazolam was observed between male and female or young and old volunteers. Rifampin significantly (P <.0001) increased the systemic and oral clearance of midazolam from 0.44 +/- 0.2 L. h/kg and 1.56 +/- 0.8 L x h/kg to 0.96 +/- 0.3 L x h/kg and 34.4 +/- 21.2 L x h/kg, respectively. Likewise, the oral clearance of midazolam was significantly (P <.0001) increased in women and men, from 1.64 +/- 0.87 L x kg/h and 1.46 +/- 0.7 L x kg/h to 28.4 +/- 13.2 L x kg/h and 41.6 +/- 26.5 L x kg/h, respectively. A significant (P =.0023) effect of sex was noted in the extent of induction of the oral clearance of midazolam, being greater in men than in women. In contrast, the extent of midazolam systemic clearance induction was greater in women than in men (P =.0107). Age did not influence the extent of intestinal and hepatic CYP3A induction as determined by the oral and systemic clearance of midazolam. Rifampin dosing significantly (P <.0001) reduced the oral availability by 88%, from 0.32 +/- 0.13 to 0.04 +/- 0.02. Correspondingly, hepatic and intestinal availabilities were significantly (P <.0001) reduced after rifampin administration. After rifampin, the correlation coefficient for the relationship between oral availability and intestinal availability was significantly (P <.0001) reduced from 0.96 to 0.67, which reflects the increasing contribution of hepatic extraction to the determination of midazolam oral availability. A significant nonlinear inverse relationship was observed between the percent change in systemic clearance of midazolam and the initial baseline midazolam systemic clearance (r = -0.68, N = 52, P <.0001). Likewise, a significant inverse relationship was observed between the percent change in oral clearance and the baseline oral clearance (r = -0.39, N = 52, P =.0041). A significant inverse relationship between the ratio of hepatic intrinsic clearance in the presence of rifampin to that in the absence of rifampin and the corresponding ratio of intestinal intrinsic clearance was observed (Spearman correlation coefficient [r] = -0.68, P <.0001) and indicates that in a given individual the extent of induction was high at either the hepatic or the intestinal site but not both. CONCLUSION: Sex-related differences exist in the extent of intestinal and hepatic CYP3A induction by rifampin. The extent of induction at hepatic and intestinal sites was inversely dependent and reflected the independent regulation of CYP3A expression at these sites. The large interindividual variation in the extent of induction is explained in part by the variation in baseline expression of CYP3A. Sex-related differences in response to CYP3A inducers will be substrate-dependent and reflect the relative contribution of hepatic and intestinal sites of metabolism.
Administration, Oral↗
Older adults with chronic disease: benefits of group-mediated counseling in the promotion of physically active lifestyles.
In this 12-month trial standard exercise training was compared with a group-mediated cognitive-behavioral (GMCB) intervention with respect to effects on long-term adherence and change in physical function of older adults who were either at risk for or had cardiovascular disease. Participants (147 older men and women) were randomized to the 2 treatments. Outcomes included self-reportedphysical activity, fitness, and self-efficacy. The GMCB treatment produced greater improvements on all outcomes than did standard exercise therapy. Regardless of treatment assignment, men had more favorable change on the study outcomes than did women. Analysis of a self-regulatory process measure in the GMCB group revealed that change in barriers efficacy was related to change in physical activity and fitness. Results suggest that teaching older adults to integrate physical activity into their lives via GMCB leads to better long-term outcomes than standardized exercise therapy.
Aged↗
Treatment with botulinum toxin type B for upper-limb spasticity.
OBJECTIVE: To determine if botulinum toxin type B (MyoBloc) decreases spasticity. DESIGN: Investigator-initiated trial, open-label, single-treatment session. SETTING: Single site. PARTICIPANTS: Ten patients with stable upper-limb spasticity and an Ashworth Scale score of 2 or higher at the elbow, wrist, and fingers. INTERVENTIONS: Total dose of 10,000U of botulinum toxin type B injected into 5 major muscles. MAIN OUTCOME MEASURES: The Ashworth Scale, goniometry, and functional assessments were performed at injection and weeks 4, 8, and 12. The principal investigator (PI) global assessment of change (GAC) and the patient GAC were done at weeks 4, 8, and 12 postinjection. The safety of the procedure was measured by adverse events and vital signs. RESULTS: Improvements in Ashworth Scale scores were observed at weeks 4, 8, and 12 postinjection. At week 4, the mean changes (in Ashworth score) were elbow, -1.0 (P=.016); wrist, -1.7 (P=.004); finger, -1.35 (P=.02); at week 8: elbow, -.83 (P=.016); wrist, -1.00 (P=.016); finger, -.94 (P=.08); and at week 12: elbow, -.61 (P=.07); wrist, -1.00 (P=.016); and finger, -.89 (P=.10). The PI GAC improved at all visits. Nine of the 10 subjects reported dry mouth at week 4, with resolution by week 12. No changes were seen on the functional measures. CONCLUSIONS: Botulinum toxin type B may be useful in treatment of spasticity.
Anti-Dyskinesia Agents↗
SIR reporting standards for the treatment of acute limb ischemia with use of transluminal removal of arterial thrombus.
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Journal Article↗
ADHD and epilepsy in childhood.
Attention-deficit-hyperactivity disorder (ADHD) has been associated with childhood epilepsy; prevalence figures have ranged from 8 to 77%, depending on the sample studied and the criteria used for diagnosis. In the general population the prevalence of ADHD is approximately 5%, with the majority of affected children having ADHD combined type. As part of a larger study of behavioral problems in children with epilepsy, we assessed 175 children (90 males, 85 females; age range 9 to 14 years, mean age was 11 years 10 months, SD 1 year 8 months) for evidence of ADHD. The children had at least a 6-month history of epilepsy. The primary caregiver completed both the Child Behavior Checklist (CBCL) and the Child Symptom Inventory-4 (CSI) or Adolescent Symptom Inventory-4 (ASI). On the CBCL, the mean attention problem T score was 64.6 (SD 10.5) for adolescents and 67.9 (SD 11.6) for children. On the CSI or ASI, 20 of 175 children met DSM-IV criteria for ADHD combined type; 42 of 175 had ADHD predominantly inattentive type; and 4 of 175 met criteria for ADHD predominantly hyperactive-impulsive type. There were significant correlations between the CBCL attention score and inattention (r = 0.68) and hyperactivity-impulsivity (r = 0.59). Sex, seizure type, and focus of seizure discharge were not predictors of symptoms of ADHD. Children with epilepsy are at risk for symptoms of ADHD. They differ from other samples of children with ADHD by the higher proportion of children with ADHD predominantly inattentive type and by an equal male: female ratio.
Adolescent↗
Intensive short courses in biostatistics for fellows and physicians.
At both of our universities we teach (with colleagues) introductory courses in statistics for fellows and physicians. We do not expect that those taking these courses will be able to do their own statistical work, but rather the intention is for them to 'learn the language' and to facilitate future collaboration. Basic principles of study design are introduced in the courses, as well as some of the most common statistical procedures. We will discuss the factors (what works and what does not) that may contribute to a successful course, a comparison to other courses, and our self-evaluation strategy. Finally, we will cover the financial arrangements that we have made when teaching these courses.
Biometry↗