Characterizing a "Big Data" Cohort of Over 200,000 Low-Income U.S. Infants and Children for Obesity Research: The ADVANCE Early Life Cohort.

Introduction Low-income populations have elevated exposure to early life risk factors for obesity, but are understudied in longitudinal research. Our objective was to assess the utility of a cohort derived from electronic health record data from safety net clinics for investigation of obesity emerging in early life. Methods We examined data from the PCORNet ADVANCE Clinical Data Research Network, a national network of Federally-Qualified Health Centers serving >1.7 million safety net patients across the US. This cohort includes patients who, in 2012-2014, had ≥1 valid body mass index measure when they were 0-5 years of age. We characterized the cohort with respect to factors required for early life obesity research in vulnerable subgroups: sociodemographic diversity, weight status based on World Health Organization (<2 years) or Centers for Disease Control (≥2 years) growth curves, and data longitudinality. Results The cohort includes 216,473 children and is racially/ethnically diverse (e.g., 17.9% Black, 45.4% Hispanic). A majority (56.9%) had family incomes below the Federal Poverty Level (FPL); 32% were <50% of FPL. Among children <2 years, 7.6 and 5.3% had high and low weight-for-length, respectively. Among children 2-5 years, 15.0, 12.7 and 2.4% were overweight, obese, and severely obese, respectively; 5.3% were underweight. In the study period, 79.2% of children had ≥2 BMI measures. Among 4-5 year olds, 21.9% had >1 BMI measure when they were <2 years. Discussion The ADVANCE Early Life cohort offers unique opportunities to investigate early life determinants of obesity in the understudied population of low income and minority children.

Restricted spirometry in the Burden of Lung Disease Study.

BACKGROUND: The presence of restrictive lung disease has classically required the measure of total lung capacity to document 'true' restriction, which has limited its detection in large population-based studies. METHODS: We used spirometric data to classify people with restricted spirometry (forced expiratory volume in 1 second [FEV(1)]/forced vital capacity ≥ 0.70 and FEV(1) < 80% predicted) in the Burden of Lung Disease (BOLD) Study and determined the relation between this finding and demographic factors and the presence of chronic diseases, including diabetes mellitus, hypertension and cardiovascular disease. RESULTS: Overall, we found that 11.7% of men (546/4664) and 16.4% of women (836/5098) had restricted spirometry. Prevalence varied widely by site, from a low of 4.2% among males in Sydney, Australia, to a high of 48.7% among females in Manila, The Philippines. Compared to people with normal lung function, those with restricted spirometry had a higher prevalence of diabetes (12.2% vs. 4.6%), heart disease (15.0% vs. 7.7%) and hypertension (38.8% vs. 22.8%). CONCLUSIONS: Restricted spirometry is a common finding in population studies. Additional research is needed to better define and describe the mechanisms that lead to restricted spirometry and potential interventions.

A simple approach to assess VT during a field walk test.

We aimed to examine whether the ventilatory threshold (VT) during an incremental shuttle walk test (ISWT) could be determined using heart rate variability (HRV) analysis. Further aims were to assess variables capable of predicting performance in the ISWT and the intensity of this test. Beat-to-beat RR intervals and gas exchange values in 10 healthy subjects (31-83 years; 7 men) were collected during the ISWT. The ventilatory equivalent was used to assess VT from respiratory components. To determine the HRV threshold (HRVT), the instantaneous beat-to-beat variability values of the RR intervals at each stage of exercise were graphically plotted against walking speed (WS). The oxygen consumption at HRVT was calculated (VO2HRVT). No significant differences were found between walking speed (WS) at VT and WS at HRVT (5.04±1.00 vs. 5.10±1.04 km/h; p=0.89). Linear regression analysis revealed a strong correlation between VO2VT and VO2HRVT (r(2)=0.896). The Bland and Altman plot analysis revealed an agreement between VO2VT and VO2HRVT (-0.05; 95%CI: -0.30-0.20 L/min). Thus, the VT can be assessed during the ISWT using a simple heart monitor. The ISWT may be a useful tool to assess exercise capacity and prescribe walking programs.

Worldwide burden of COPD in high- and low-income countries. Part I. The burden of obstructive lung disease (BOLD) initiative.

SETTING: Burden of Obstructive Lung Disease (BOLD) Initiative sites worldwide. OBJECTIVE: To measure the prevalence of chronic obstructive pulmonary disease (COPD) and its risk factors, investigate variation in prevalence across countries and develop standardized methods that can be used in industrialized and developing countries. DESIGN: Non-institutionalized adults aged > or =40 years were recruited using population-based sampling plans. Each site targeted a minimum of 600 participants (300 women, 300 men), who filled out questionnaires and performed spirometry before and after administration of 200 mug salbutamol using standardized methods. Random effects meta-analysis models were used to estimate pooled prevalence estimates and risk factor effects and to test for heterogeneity across sites and sex. RESULTS: Data published from 12 sites (n = 8775) showed that the estimated population prevalence of COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stage II and higher) was 10.1 +/- SE = 4.8% overall (11.8 +/- 7.9% for men and 8.5 +/- 5.8% for women). Prevalence increased with age and pack-years of smoking, but other less understood risk factors, such as biomass heating and cooking exposures, occupational exposures and tuberculosis, also contribute to the location-specific variations in disease prevalence that BOLD is finding. CONCLUSION: BOLD has estimated the social and economic burden of COPD in 12 countries to date. BOLD and the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar (the PLATINO study) are developing a growing database of COPD prevalence. Cigarette smoking and age are the most important COPD risk factors, but other risk factors should also be explored.

Public-access defibrillation and survival after out-of-hospital cardiac arrest.

BACKGROUND: The rate of survival after out-of-hospital cardiac arrest is low. It is not known whether this rate will increase if laypersons are trained to attempt defibrillation with the use of automated external defibrillators (AEDs). METHODS: We conducted a prospective, community-based, multicenter clinical trial in which we randomly assigned community units (e.g., shopping malls and apartment complexes) to a structured and monitored emergency-response system involving lay volunteers trained in cardiopulmonary resuscitation (CPR) alone or in CPR and the use of AEDs. The primary outcome was survival to hospital discharge. RESULTS: More than 19,000 volunteer responders from 993 community units in 24 North American regions participated. The two study groups had similar unit and volunteer characteristics. Patients with treated out-of-hospital cardiac arrest in the two groups were similar in age (mean, 69.8 years), proportion of men (67 percent), rate of cardiac arrest in a public location (70 percent), and rate of witnessed cardiac arrest (72 percent). No inappropriate shocks were delivered. There were more survivors to hospital discharge in the units assigned to have volunteers trained in CPR plus the use of AEDs (30 survivors among 128 arrests) than there were in the units assigned to have volunteers trained only in CPR (15 among 107; P=0.03; relative risk, 2.0; 95 percent confidence interval, 1.07 to 3.77); there were only 2 survivors in residential complexes. Functional status at hospital discharge did not differ between the two groups. CONCLUSIONS: Training and equipping volunteers to attempt early defibrillation within a structured response system can increase the number of survivors to hospital discharge after out-of-hospital cardiac arrest in public locations. Trained laypersons can use AEDs safely and effectively.

Estrogen replacement and brachial artery flow-mediated vasodilation in older women.

It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.

Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter.

BACKGROUND: Brachial artery ultrasound has been proposed as an inexpensive, accurate way to assess cardiovascular risk in populations. However, analysis and interpretation of these data are not uniform. METHODS: We analysed the relationship between relative and absolute changes in brachial artery diameter in response to flow-mediated dilation and age, gender and baseline diameter among 4,040 ultrasound examinations from subjects aged 14 to 98 years. RESULTS: Reproducibility studies demonstrated intra- and interreader and intrasubject correlations from 0.67 to 0.84 for repeated measures of per cent change in diameter. Per cent change in diameter after flow stimulus was 3.58 +/- 0.10% (mean +/- standard deviation). Corresponding values for baseline diameter and absolute change in diameter were 4.43 +/- 0.87 mm and 0.15 +/- 0.01 mm, respectively. Baseline diameter and its variance were inversely related to per cent change in diameter (P< 0.001). In contrast, absolute change in diameter was more uniform throughout the range of baseline diameters. Baseline diameter was directly related, and per cent change in diameter inversely related, to age (P < 0.001 for all three measures). Time to maximum vasodilator response increased with age (P < 0.001). Women (n=2,315) had significantly larger per cent change in diameter than men (n=1,725) (P < 0.001). However, after adjustment for age and baseline diameter, per cent and absolute change were 5% smaller in women than men (P < 0.05 for both). In multivariate analysis, age was overwhelmingly the most important determinant of absolute change in diameter (P < 0.001). CONCLUSIONS: Automated analysis of brachial flow-mediated vasodilator responses is both feasible and reproducible in large-scale clinical and population-based research.

Frailty in older adults: evidence for a phenotype.

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

Associations of subclinical cardiovascular disease with frailty.

BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology. METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing. RESULTS: Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05). CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.

Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort.

PURPOSE: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation. SUBJECTS AND METHODS: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995. RESULTS: In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0). CONCLUSIONS: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

Efficacy of aerosolized tobramycin in patients with cystic fibrosis.

BACKGROUND: Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections. METHODS: Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored. RESULTS: In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration. CONCLUSIONS: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.

Physical growth of children treated for phenylketonuria.

The growth of 133 children participating in the Collaborative Study of Children Treated for Phenylketonuria (PKU) was compared to growth data from the National Center for Health Statistics (NCHS) to determine whether the growth patterns of the children with PKU were the same as those of unaffected children. Height and weight by age, and weight by height, were analysed for ages 2-10 years. Head circumference by age was analysed for ages 2-7 years. Median height by age of the PKU children was consistently near the 50th percentile of the NCHS growth curves for males and females. However, for both sexes, median weight by height and by age was between the 50th and 75th percentiles for children over 3 years old. Two-sample t-tests showed mean weight was significantly different (p less than 0.05) between the PKU and NCHS groups at most ages for both sexes. Median head circumference for the PKU children tended to be smaller than NCHS standards; however, the maximum difference at any age was less than 0.5 cm. Polynomial growth curves fitted to the PKU and NCHS growth data showed that, on average, the PKU males and females weighed more than their unaffected counterparts, while height and head circumference for both groups were very close. Including median serum phenylalanine (phe) level (mg/dl) in the growth curves suggested that the weight differences between the PKU and NCHS groups are related to degree of diet adherence. Higher phe levels in the PKU group were associated with higher weight levels, more so for girls (p less than 0.001) than for boys (p = 0.08). No relationship was found between phe level and height or head circumference. We conclude that growth in children treated for PKU differs from national standards for weight by age and weight by height, but not for height by age. We speculate that diet adherence may be an important factor in determining which children have a tendency to become overweight.