Myra A. Carpenter

Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial

OBJECTIVES. There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux. METHODS. One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans. RESULTS. The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis. CONCLUSIONS. Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV.

Dietary Antioxidants and Carotid Artery Wall Thickness The ARIC Study

BACKGROUND Evidence that dietary antioxidants may prevent atherosclerotic disease is growing. The relationship between the intake of dietary and supplemental vitamin C, alpha-tocopherol, and provitamin A carotenoids and average carotid artery wall thickness was studied in 6318 female and 4989 male participants 45 to 64 years old int he Atherosclerosis Risk in Communities Study. METHODS AND RESULTS Intake was assessed by use of a 66-item semiquantitative food-frequency questionnaire. Carotid artery intima-media wall thickness was measured as an indicator of atherosclerosis at multiple sites with B-mode ultrasound. Among men and women > 55 years old who had not recently begun a special diet, there was a significant inverse relationship between vitamin C intake and average artery wall thickness adjusted for age, body mass index, fasting serum glucose, systolic and diastolic blood pressures, HDL and LDL cholesterol, total caloric intake, cigarette use, race, and education (test for linear trend across quintiles of intake, P = .019 for women and P = .035 for men). An inverse relationship was also seen between wall thickness and alpha-tocopherol intake but was significant only in women (test for linear trend, P = .033 for women and P = .13 for men). There was a significant inverse association between carotene intake and wall thickness in older men (test for linear trend, P = .015), but the association weakened after adjustment for potential confounders. No significant relationships were seen in participants < 55 years old. CONCLUSIONS These data provide limited support for the hypothesis that dietary vitamin C and alpha-tocopherol may protect against atherosclerotic disease, especially in individuals > 55 years old.

Laboratory, Reading Center, and Coordinating Center Data Management Methods in the Jackson Heart Study

Background:Cardiovascular disease (CVD) is the leading cause of death in the United States. In comparison to whites, African-Americans have a higher risk of dying from CVD and have a worse risk factor profile. The Jackson Heart Study (JHS) is designed to investigate the origin and natural history of CVD in African-Americans. Methods:Reading centers for electrocardiograms, echocardiograms, carotid ultrasonograms, pulmonary function tests, and ambulatory blood pressure monitoring provide training for data accrual, quality assurance assessments, and specialized measurements for research objectives. Laboratories adhering to well-established quality assurance programs provide blood and urine analyses, as well as storage of specimens for future assays. A new Coordinating Center was created to perform functions analogous to those of coordinating centers for multisite studies, including protocol development, data management, statistical analyses, and operational support for the study. An established coordinating center serves as a resource to the JHS Coordinating Center, providing assistance in preparing procedure manuals and data collection forms. This group also designed and developed the JHS data management system. Results:This network of specialized research organizations is implementing state- of-the-science methodologies to assess prevalence, progression, and incidence of CVD and subclinical atherosclerosis, and to evaluate a myriad of risk factors. From November 2000 through March 2004, JHS collected 4000 data fields on each of more than 5300 African-American participants. Conclusions:This article describes the roles of specialized research agencies contributing to JHS, and the methodologies being utilized to accumulate study data. A diverse collection of scientific disciplines is required to collect the information needed to meet the objectives of the JHS.

Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients Primary Results From the Folic Acid for Vascular Outcome Reduction in Transplantation Trial

Background— Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. Methods and Results— In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. Conclusions— Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00064753.

Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients

Background— Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. Methods and Results— In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. Conclusions— Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00064753.

Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND Although much has been written in recent years about the relation between alcohol and atherosclerotic disease, controversy exists as to whether and how alcohol exerts an effect on atherosclerosis in different sites. METHODS AND RESULTS We tested the hypothesis that alcohol consumption is associated inversely with carotid atherosclerosis in a population sample of 45- to 64-year-old men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study and were free of cardiovascular disease at a baseline examination in 1987 to 1989. B-mode ultrasonography was used to determine carotid artery intimal-medial wall thickness and distensibility as indices of the degree of atherosclerosis. The level of alcohol consumption in the ARIC sample was generally low. Age-adjusted mean values of alcohol consumed (grams per week) were 72.0 for white and 74.3 for nonwhite men and 24.8 for white and 11.2 for nonwhite women. After adjustments for age, artery depth, education, body mass index, sport index, cigarette-years of smoking, low-density lipoprotein cholesterol, and diabetes mellitus, there was no significant cross-sectional association of reported current alcohol intake with either carotid artery wall thickness (among white and nonwhite men and nonwhite women) or distensibility (in any of the four sex-race groups). Among white women, the adjusted mean value of carotid artery wall thickness tended to be higher in light to moderate drinkers than in never or rare drinkers, but the difference across drinking status categories was of borderline statistical significance (P = .04) and may be of little biological importance. CONCLUSIONS The ARIC Study found no material cross-sectional association between current alcohol intake and carotid atherosclerosis but provides an opportunity in the future to study atherosclerosis progression and incident events in relation to alcohol consumption in a large population sample of men and women.

Correlates of body fat distribution: Variation across categories of race, sex, and body mass in the atherosclerosis risk in communities study

Though central adiposity is a strong, independent risk factor for cardiovascular and all-cause mortality, relatively little is known about its determinants. To characterize the association of central adiposity with several of its possible determinants, while describing variability in these associations across sex, race, and level of body mass index, we conducted a cross-sectional survey of 15,800 white and African-American men and women ages 45 to 64 years participating in the Atherosclerosis Risk in Communities baseline survey, 1987 to 1989. After adjustment for other possible determinants, African Americans had markedly larger subscapular skinfold thickness and subscapular/triceps ratios than did whites, while whites had larger waist/hip ratios. Large, statistically significant variations in waist/hip ratio associations with age, percent of weight gained after age 25, smoking, and physical activity in the workplace existed across categories of sex, race, and body mass index. Based on our findings, we concluded that major variation exists in the waist/hip ratio and in its associations with its possible determinants across categories of race, sex and obesity.

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all‐cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49±18 mL/min/1.73 m2. In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m2 higher eGFR at levels below 45 mL/min/1.73 m2 was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m2. In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.

The RIVUR Trial: Profile and Baseline Clinical Associations of Children With Vesicoureteral Reflux

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is diagnosed in ∼30% to 40% of children who have imaging studies after urinary tract infections (UTIs). Our goal is to characterize children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial and to compare our study cohort with those from previously published studies. METHODS: RIVUR investigators from 19 pediatric sites in the United States recruited 607 children with grade I through IV VUR. Children were enrolled after a first or second UTI. This cross-sectional report of baseline data includes extensive clinical, parental report, and imaging study results. RESULTS: RIVUR recruited 607 children (558 girls, 49 boys) with grade I (11%), II (42%), III (38%), or IV (8%) reflux. The median age was 12 months, and most children (91%) were enrolled after their first UTI. The UTI leading to enrollment was both febrile and symptomatic for 323 children, febrile only in 197 children, and symptomatic only in 86. Renal involvement at baseline as documented by a 99mTc dimercaptosuccinic acid scan was uncommon with cortical defects identified in 89 (15%) children. Bladder and bowel dysfunction was identified in 71 (56%) of 126 toilet-trained subjects assessed. CONCLUSIONS: RIVUR is the largest prospective, randomized trial for children with primary VUR to date, comparing prophylaxis with placebo. The study sample comprises patients from 19 pediatric clinical sites in the United States, whose demographic and clinical characteristics may differ from those of children enrolled in previous trials from other countries.

Factors That Influence Parental Decisions to Participate in Clinical Research: Consenters vs Nonconsenters

IMPORTANCE A childs health, positive perceptions of the research team and consent process, and altruistic motives play significant roles in the decision-making process for parents who consent for their child to enroll in clinical research. This study identified that nonconsenting parents were better educated, had private insurance, showed lower levels of altruism, and less understanding of study design. OBJECTIVE To determine the factors associated with parental consent for their childs participation in a randomized, placebo-controlled trial. DESIGN Cross-sectional survey conducted from July 2008 to May 2011. The survey was an ancillary study to the Randomized Intervention for Children with VesicoUreteral Reflux Study. SETTING Seven childrens hospitals participating in a randomized trial evaluating management of children with vesicoureteral reflux. PARTICIPANTS Parents asked to provide consent for their childs participation in the randomized trial were invited to complete an anonymous online survey about factors influencing their decision. A total of 120 of the 271 (44%) invited completed the survey; 58 of 125 (46%) who had provided consent and 62 of 144 (43%) who had declined consent completed the survey. MAIN OUTCOMES AND MEASURES A 60-question survey examining child, parent, and study characteristics; parental perception of the study; understanding of the design; external influences; and decision-making process. RESULTS Having graduated from college and private health insurance were associated with a lower likelihood of providing consent. Parents who perceived the trial as having a low degree of risk, resulting in greater benefit to their child and other children, causing little interference with standard care, or exhibiting potential for enhanced care, or who perceived the researcher as professional were significantly more likely to consent to participate. Higher levels of understanding of the randomization process, blinding, and right to withdraw were significantly positively associated with consent to participate. CONCLUSIONS AND RELEVANCE Parents who declined consent had a relatively higher socioeconomic status, had more anxiety about their decision, and found it harder to make their decision compared with consenting parents, who had higher levels of trust and altruism, perceived the potential for enhanced care, reflected better understanding of randomization, and exhibited low decisional uncertainty. Consideration of the factors included in the conceptual model should enhance the quality of the informed consent process and improve participation in pediatric clinical trials.