Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To determine whether weight extremes impact clinical outcomes in pediatric acute respiratory distress syndrome. DESIGN: Post hoc analysis of a cohort created by combining five multicenter pediatric acute respiratory distress syndrome studies. SETTING: Forty-three academic PICUs worldwide. PATIENTS: A total of 711 subjects prospectively diagnosed with pediatric acute respiratory distress syndrome. INTERVENTION: Subjects more than 2 years were included and categorized by Center for Disease Control and Prevention body mass index z score criteria: underweight (< -1.89), normal weight (-1.89 to +1.04), overweight (+1.05 to +1.64), and obese (≥ +1.65). Subjects were stratified by direct versus indirect lung injury leading to pediatric acute respiratory distress syndrome. The primary outcome was in-hospital mortality. In survivors, secondary analyses included duration of mechanical ventilation and ICU length of stay. MEASUREMENTS AND MAIN RESULTS: A total of 331 patients met inclusion criteria; 12% were underweight, 50% normal weight, 11% overweight, and 27% obese. Overall mortality was 20%. By multivariate analysis, body mass index category was independently associated with mortality (p = 0.004). When stratified by lung injury type, there was no mortality difference between body mass index groups with direct lung injury; however, in the indirect lung injury group, the odds of mortality in the obese were significantly lower than normal weight subjects (odds ratio, 0.11; 95% CI, 0.02-0.84). Survivors with direct lung injury had no difference in the duration of mechanical ventilation or ICU length of stay; however, those with indirect lung injury, the overweight required longer duration of mechanical ventilation than other groups (p < 0.001). CONCLUSIONS: These data support the obesity paradox in pediatric acute respiratory distress syndrome. Obese children with indirect lung injury pediatric acute respiratory distress syndrome have a lower risk of mortality. Importantly, among survivors, the overweight with indirect lung injury requires longer duration of mechanical ventilation. Our data require prospective validation to further elucidate the pathobiology of this phenomenon.

HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity.

HDL is the primary mediator of cholesterol mobilization from the periphery to the liver via reverse cholesterol transport (RCT). A critical first step in this process is the uptake of cholesterol from lipid-loaded macrophages by HDL, a function of HDL inversely associated with prevalent and incident cardiovascular disease. We hypothesized that the dynamic ability of HDL to undergo remodeling and exchange of apoA-I is an important and potentially rate-limiting aspect of RCT. In this study, we investigated the relationship between HDL-apoA-I exchange (HAE) and serum HDL cholesterol (HDL-C) efflux capacity. We compared HAE to the total and ABCA1-specific cholesterol efflux capacity of 77 subjects. We found that HAE was highly correlated with both total (r = 0.69, P < 0.0001) and ABCA1-specific (r = 0.47, P < 0.0001) efflux, and this relationship remained significant after adjustment for HDL-C or apoA-I. Multivariate models of sterol efflux capacity indicated that HAE accounted for approximately 25% of the model variance for both total and ABCA1-specific efflux. We conclude that the ability of HDL to exchange apoA-I and remodel, as measured by HAE, is a significant contributor to serum HDL efflux capacity, independent of HDL-C and apoA-I, indicating that HDL dynamics are an important factor in cholesterol efflux capacity and likely RCT.

Indicators of sequential fitness assessment failures for Travis Air Force Base airmen who attend the Be Well Course.

PURPOSE: This retrospective community intervention trial evaluated the Be Well course--a mandatory lifestyle intervention course for airmen who fail the U.S. Air Force fitness assessment (FA)--at Travis Air Force Base from November 1, 2010 to February 1, 2011. METHODS: Pre-existing data (N = 276) were analyzed for change in FA scores and for predictors of future outcomes. RESULTS: On the subsequent FA after completing Be Well, males and females scored significantly higher on total points, aerobic fitness, push-ups, and sit-ups (p < 0.001 for all), and males had lower body mass indices (BMI; p = 0.005) and smaller abdominal circumferences (AC; p < 0.001), as compared to their initial FA. As opposed to those who passed the subsequent FA, those who failed consecutively had significantly higher BMIs (p < 0.001), larger ACs (p < 0.001), and lower total scores (p < 0.0001) at the time of the initial failure. CONCLUSIONS: The Be Well course is an effective tool and should remain a component of remedial training for airmen who fail the Air Force FA. Stratification of failure should be considered at the policy level, with special consideration given to the risk factors of high BMI, large AC, and low total FA score.

Randomized controlled trial of a breath-actuated nebulizer in pediatric asthma patients in the emergency department.

BACKGROUND: Bronchodilator treatment for asthma can be provided with various aerosol-generating devices and methods. There have been no randomized trials of a breath-actuated nebulizer versus continuous 1-hour nebulization and/or small-volume constant-output nebulizer in pediatric asthma patients. METHODS: We conducted a randomized study of one-time albuterol treatment with the AeroEclipse breath-actuated nebulizer versus standard therapy (single treatment via small-volume nebulizer or 1-hour of continuous nebulized albuterol) in pediatric asthma patients in the emergency department. Eligible patients were those admitted to the emergency department, 0 months to 18 years of age, who presented with asthma or wheezing. We assessed all the patients with our clinical asthma scoring system and peak-flow measurement if possible. We stratified the patients by clinical asthma score and weight, and then randomized them to receive their initial albuterol treatment in the emergency department via either AeroEclipse or standard therapy. We recorded time in the emergency department, change in clinical asthma score, need for additional bronchodilator treatments, need for admission, patient response, ability to actuate the AeroEclipse, and adverse effects. RESULTS: We enrolled 149 patients between October 14, 2004 and November 11, 2005, and we randomized 84 patients to AeroEclipse and 65 to standard therapy. The cohort's average age was 5.5 years. There were no significant differences in demographics. The initial mean clinical asthma scores were 5.1 ± 2.4 in the AeroEclipse group, and 5.1 ± 2.1 in the standard-therapy group. Time in the emergency department was not different (AeroEclipse 102 min, standard therapy 125 min, P = .10), but the AeroEclipse group had a significantly greater improvement in clinical asthma score (1.9 ± 1.2 vs 1.2 ± 1.4, P = .001) and respiratory rate (P = .002), and significantly lower admission rate (38% vs 57%, P = .03). There was no difference in adverse effects. CONCLUSIONS: Although AeroEclipse did not reduce the time in the ED, it significantly improved clinical asthma score, decreased admissions, and decreased respiratory rate.

The Type of Dietary Fat in an Isocaloric Breakfast Meal Does Not Modify Postprandial Metabolism in Overweight/Obese Pregnant Women.

Almonds provide a satiating, healthy source of fat and fiber. The postprandial metabolic and satiety response to 2 ounces of nuts or dairy was assessed in 18 overweight/obese women during late pregnancy. Serum glucose, triglycerides, insulin, c-peptide, leptin, ghrelin, and lipoprotein particles were measured prior to and during a 5-h postprandial period following the consumption of an isocaloric breakfast meal with equivalent amounts of fat from either nuts or dairy on two separate mornings. Satiety was assessed by visual analogue scale (VAS) questionnaires and ad libitum food intake at the end of the study. At 33 weeks gestation, the women had gained an average of 7.0 ± 4.4 kg during gestation. Body fat averaged 41.9 ± 5.5% and hemoglobin A1c levels were elevated, (7.2 ± 0.6%). Fasting glucose levels were normal, but hyperinsulinemia was evident. The two test meals did not affect the postprandial metabolic response, but glucose, triglyceride, and ghrelin concentrations changed with time during the postprandial period (p < 0.001, p = 0.0008, p = 0.006). Satiety measures did not differ between the two test meals. Consuming an isocaloric breakfast meal with equivalent amounts of fat from nuts or dairy did not alter postprandial levels of blood lipids, glucose, hormones, or measures of satiety in overweight/obese, pregnant women.

A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations.

BACKGROUND: Food fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status. OBJECTIVE: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status. DESIGN: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period. RESULTS: TAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase. CONCLUSIONS: A moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352.

Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood.

BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization. METHODS: Children from a 2006 to 2010 maternal-infant cohort were eligible for the current study. Children were screened for malaria, schistosomiasis, filariasis, intestinal helminths, and protozoa. Data on in utero exposure and early life infections were linked, and baseline antipneumococcal immunoglobulin G levels and nasopharyngeal carrier status were determined. Participants received decavalent pneumococcal vaccine, and 4 weeks later, serology was repeated to assess vaccine response. RESULTS: A total of 281 children were included. Preimmunity was associated with greater postvaccination increments in anti-pneumococcal polysaccharide immunoglobulin G, especially serotypes 4, 7, 9, 18C, and 19. Present-day growth stunting was independently associated with weaker responses to 1, 4, 6B, 7, 9V, and 19. Previous exposure to Trichuris was associated with stronger responses to 1, 5, 6B, 7, 18C, and 23, but other parasite exposures were not consistently associated with response. CONCLUSIONS: In our cohort, hyporesponsiveness to pneumococcal conjugate vaccine was associated with growth stunting but not parasite exposure. Parasite-related vaccine response deficits identified before age 3 do not persist into later childhood.

Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis.

BACKGROUND: Pregnancy induces drastic biological changes systemically, and has a beneficial effect on some autoimmune conditions such as rheumatoid arthritis (RA). However, specific systemic changes that occur as a result of pregnancy have not been thoroughly examined in healthy women or women with RA. The goal of this study was to identify genes with expression patterns associated with pregnancy, compared to pre-pregnancy as baseline and determine whether those associations are modified by presence of RA. RESULTS: In our RNA sequencing (RNA-seq) dataset from 5 healthy women and 20 women with RA, normalized expression levels of 4,710 genes were significantly associated with pregnancy status (pre-pregnancy, first, second and third trimesters) over time, irrespective of presence of RA (False Discovery Rate (FDR)-adjusted p value<0.05). These genes were enriched in pathways spanning multiple systems, as would be expected during pregnancy. A subset of these genes (n = 256) showed greater than two-fold change in expression during pregnancy compared to baseline levels, with distinct temporal trends through pregnancy. Another 98 genes involved in various biological processes including immune regulation exhibited expression patterns that were differentially associated with pregnancy in the presence or absence of RA. CONCLUSIONS: Our findings support the hypothesis that the maternal immune system plays an active role during pregnancy, and also provide insight into other systemic changes that occur in the maternal transcriptome during pregnancy compared to the pre-pregnancy state. Only a small proportion of genes modulated by pregnancy were influenced by presence of RA in our data.

Smoking cessation counseling with young patients: the practices of family physicians and pediatricians.

OBJECTIVE: To investigate family physicians' and pediatricians' practice of and perceived barriers to smoking cessation counseling among patients 18 years and younger. DESIGN: Cross-sectional mail survey conducted between November 1, 1997, and January 31, 1998. PARTICIPANTS: A stratified random sample selected from the 1997 American Medical Association Physician Masterfile of 1000 family physicians and pediatricians who practice in urban California, work at least 10% of the time in ambulatory care, and have at least 10% of patients 18 years and younger. MAIN OUTCOME MEASURES: Physicians' adherence to 5 components of the National Cancer Institute's smoking cessation counseling recommendations (anticipate, ask, advise, assist, and arrange) and their perceived barriers to smoking cessation counseling. RESULTS: A total of 429 physicians participated in the study. Physicians of both specialties were more likely to anticipate, ask, and advise patients about smoking than to assist with and arrange cessation activities. Family physicians were more likely than pediatricians to assist and arrange, including scheduling follow-up visits to discuss quitting (25.1% vs 11.7%; odds ratio [OR], 3.07; 95% confidence interval [CI], 1.22-7.73) and directing nursing staff to counsel patients (17.1% vs 10.9%; OR, 3.70; 95% CI, 1.30-10.60). The most common perceived barrier to counseling was the belief that children would provide inaccurate responses due to either the presence of parents (86.4%) or the fear that parents would be notified of their answers (74.0%). Pediatricians reported lack of counseling skills as a barrier to providing smoking interventions in greater proportion than did family physicians (24.9% vs 54.8%; OR, 0.29; 95% CI, 0.14-0.63; P<.001). CONCLUSION: Improvement in smoking cessation counseling skills and practices is needed among physicians treating children and adolescents.

Assessment of demand for prenatal diagnostic testing using willingness to pay.

OBJECTIVE: To investigate the demand for invasive prenatal diagnostic testing (amniocentesis and chorionic villous sampling) in a racially/ethnically diverse group of pregnant women of all ages in the San Francisco Bay Area by using estimates of willingness to pay for these procedures. METHODS: We surveyed 447 women of varying ages, ethnicity, and socioeconomic levels to assess their desire to undergo and willingness to pay for invasive prenatal testing for chromosomal disorders. Each woman was asked what she would be willing to pay for invasive diagnostic testing up to the full cost of the procedure. We also asked several demographic and attitudinal questions. RESULTS: Overall, 49% of the women indicated an interest in undergoing invasive prenatal diagnostic testing. Women aged 35 years and older were more likely to desire testing as compared with women aged less than 35 years (72% versus 36%, P <.001). Of the women aged less than 35 years who desired testing, 31% indicated that they would be willing to pay the full price of $1,300, whereas 73% were willing to pay a portion of the cost. Maternal age of 35 years or greater (odds ratio [OR] 3.3; 95% confidence interval [CI] 2.0, 5.6) and willingness to have an elective abortion (OR 2.8; 95% CI 1.6, 4.9) were significant predictors of desire to undergo prenatal diagnostic testing after controlling for income, race/ethnicity, and education. Maternal age of 35 years or greater (OR 3.5; 95% CI 1.59, 7.88) and having an income greater than $35,000 (OR 2.3; 95% CI 1.02, 5.26) were significant predictors of willingness to pay the full price of testing. CONCLUSION: A substantial proportion of women of all ages indicate a desire to undergo and a willingness to pay for prenatal diagnostic testing. Variations in willingness to pay are correlated with both socioeconomic and attitudinal differences in addition to age. Guidelines regarding use of prenatal genetic diagnosis should be expanded to offer testing to all women, not just those deemed at increased risk. LEVEL OF EVIDENCE: II-2

How do women of diverse backgrounds value prenatal testing outcomes?

OBJECTIVES: To describe women's preferences for prenatal testing outcomes and to explore their association with sociodemographic characteristics and attitudes. METHODS: We conducted a cross-sectional study of 584 racially/ethnically and socioeconomically diverse pregnant women aged 16 to 47 years recruited from 23 San Francisco Bay Area practices. We assessed preferences for 12 potential prenatal testing outcomes using the time trade-off metric for all outcomes and the standard gamble metric for two outcomes. Preferences were calculated on a scale of 0 (death) to 1 (perfect health). Participants also completed a sociodemographic and attitude survey. RESULTS: Highest preference scores were assigned to outcomes resulting in the birth of a chromosomally normal infant (mean = 0.91-0.93; median = 0.99-1.00). Lower scores were obtained for outcomes involving pregnancy loss (mean = 0.69-0.87; median = 0.76-0.92), which were correlated with attitudes regarding miscarriage, pregnancy termination, and Down syndrome. The lowest scores were assigned to Down syndrome-affected births (mean = 0.67-0.69; median = 0.73-0.75), which also were correlated with attitudes toward Down syndrome. We did not find a statistically significant relationship between participants' preference scores and age. CONCLUSION: Preferences for prenatal testing outcomes vary according to the pregnant women's underlying attitudes about pregnancy loss and Down syndrome, and not according to her age. Current age/risk-based guidelines should account for individual variation in patient preferences.

Social and familial context of prenatal genetic testing decisions: are there racial/ethnic differences?

The purpose of this cross-sectional study of 999 socioeconomically and racially/ethnically diverse pregnant women was to explore prenatal genetic testing attitudes and beliefs and the role of external influences. Surveys in English, Spanish, and Chinese included questions regarding the value of testing, pregnancy, and motherhood; the acceptability of Down syndrome in the subject's community; and the role of social and cultural influences in prenatal testing decisions. We analyzed racial/ethnic differences in all attitudinal and external influence variables, controlling for age, relationship status, and socioeconomic status. We found statistically significant racial/ethnic group differences in familiarity with an individual with Down syndrome and in 10 of 12 attitude, belief, and external influence variables, even after controlling for other sociodemographic characteristics. We also observed substantial variation within racial/ethnic groups for each of these measures. Despite the statistically significant group differences observed, R(2) values for all multivariate models were modest and response distributions overlapped substantially. Social and familial contexts for prenatal testing decisions differ among racial/ethnic groups even after accounting for age, marital status, and other socioeconomic factors. However, substantial variation within groups and overlap between groups suggest that racial/ethnic differences play a small role in the social and familial context of prenatal genetic testing decisions.