Justine Shults

We consider a longitudinal study of interstitial cystitis (IC) in women, in which the time between bouts of repeated measurements is large relative to the within-bout separation in time. Our outcome of interest is the number of nocturnal voids that we model via quasi-least squares (QLS) in the framework of generalized estimating equations (GEE). To account for potential intra-subject correlation, we directly apply a banded Toeplitz correlation structure that previously was only implemented in an ad hoc approach using GEE. We describe this structure, its appropriateness for data from the IC study, and the results of our analysis. We then demonstrate that correct specification of the underlying correlation structure versus incorrectly applying a simpler structure can prevent substantial losses in efficiency in estimation of the regression parameter. These comparisons involve the limiting values of the estimates of the correlation parameters, which are not consistent for the misspecification scenarios considered here. We therefore obtain the limiting values of the QLS estimates when the structure is incorrectly specified.

Increased levels of dopamine transporter (DAT) binding have been reported in patients with major depression. We used the selective DAT radiopharmaceutical Tc-TRODAT-1 and SPECT brain imaging, to examine differences in DAT levels in healthy subjects with and without depressive affect. We compared striatal DAT binding affinity in 73 healthy subjects to their scores on the depressive symptoms subscale of the Profile of Mood States (POMS). Regions of interest in the basal ganglia of the brain were examined. Distribution volume ratios (DVRs) of Tc-TRODAT-1 binding affinity were calculated from the SPECT scan data, and comparisons among subjects with low and high depressive symptom ratings were calculated using unpaired t-tests and the Pearson correlation. We observed a greater Tc-TRODAT-1 DVR in the right caudate of subjects with high POMS mood scores compared to subjects with low scores on depressive items on the POMS (2.99+/-0.35 and 2.79+/-0.35, respectively; P=0.009). There was also a weak, but significant correlation between higher Tc-TRODAT-1 DVRs in the right caudate and depressive symptoms scores (r=0.23, P=0.05). These data suggest that Tc-TRODAT-1 binding affinity to DAT sites may be associated with depressive affect in healthy subjects. The finding also supports prior observations of greater Tc-TRODAT-1 DVRs in patients with major depressive episode.

Retrospective studies have limitations in predicting perioperative risk following adenotonsillectomy in children with obstructive sleep apnea syndrome (OSAS). Few prospective studies exist. We hypothesized that demographic and polysomnographic (PSG) variables would predict respiratory and general perioperative complications. Prospective, observational cohort study. Pediatric tertiary center. Consecutive children undergoing adenotonsillectomy for OSAS within 12 months of PSG were evaluated for complications occurring within 2 weeks of surgery. There were 329 subjects, with 27% <3 years old, 24% obese, 16% preterm, and 29% with comorbidities. In this higher risk population, 28% had respiratory complications (major and/or minor), and 33% had nonrespiratory complications. Significant associations were found between PSG parameters and respiratory complications as follows: apnea hypopnea index (rank-biserial correlation coefficient [r] = 0.174, P = .017), SpO2 nadir (r = -0.332, P <...

Children with the obstructive sleep apnea syndrome (OSAS) have impaired respiratory afferent cortical processing during sleep that persists after treatment of OSAS. However, it is unknown whether this impairment is present during wakefulness and, if so, whether it improves after OSAS treatment. We hypothesized that children with OSAS, during wakefulness, have abnormal cortical processing of respiratory stimuli manifested by blunted respiratory-related evoked potentials (RREP) and that this resolves after OSAS treatment. We measured RREP during wakefulness in 26 controls and 21 children with OSAS before and after treatment. Thirteen participants with OSAS repeated testing 3-6 mo after adenotonsillectomy. RREP were elicited by interruption of inspiration by total occlusion and 30 and 20 cmH2O/l per s resistances. Nf at Fz latency elicited by occlusion was longer in children with OSAS at baseline compared with controls (78.8 ± 24.8 vs. 63.9 ± 19.7 ms, P = 0.05). All other peak amplitud...

In adults, osteoarthritis (OA) is associated with obesity and knee alignment. Whether knee alignment differences develop during childhood and are associated with obesity is unknown. We assessed the distribution of knee alignment in children and adolescents, and determined how knee alignment differs between obese and nonobese children. This cross-sectional study examined knee alignment in 155 healthy weight and 165 obese subjects. Knee alignment [metaphyseal-diaphyseal angle (MDA) and anterior tibiofemoral angle (ATFA)] and fat mass were measured using whole body dual-energy X-ray absorptiometry (DEXA). National reference data were used to generate age- and sex-specific body mass index (BMI, kg/m(2)) Z-scores. Multivariable linear regression was used to identify independent factors associated with ATFA and MDA. The mean MDA and ATFA were similar between obese and nonobese subjects. In stratified analyses, females had greater variability in MDA and ATFA values (p < 0.001 and p = 0.04, respectively) at higher BMI Z-scores. Compared with healthy weight controls, obese subjects had less valgus of the MDA prior to the onset of puberty (+ 2.0°, p = 0.001), but had greater valgus at later pubertal stages (-1.9°, p = 0.01). We found significantly greater variability in knee alignment among females at higher BMI Z-scores, and greater valgus alignment in obese adolescents in late puberty. The major limitation is the use of DEXA for assessment of alignment, which needs validation against longstanding radiographs. Longitudinal studies are needed to determine whether childhood obesity is a risk factor for progressive malalignment that may predispose to pain and risk of early osteoarthritis.

Vitamin D deficiency is a potential risk factor for autoimmunity. Prior studies of the association between vitamin D levels and rheumatoid arthritis (RA) disease activity have yielded conflicting results. Serum 25(OH)vitamin D levels were measured at baseline in 499 participants with active RA, ages 18-85 years, enrolled in a randomised clinical trial of golimumab (Go-Before Trial). Subjects were methotrexate and biologic therapy naïve. Multivariable linear regression was used to assess associations between vitamin D levels and disease activity scores (DAS28), van der Heijde-Sharp (vdHS) erosion scores, and serum inflammatory markers. Generalised estimating equations were used to evaluate the associations between vitamin D status and the response to therapy over 52 weeks, using the DAS28 and ACR response. Forty-eight percent of participants were vitamin D deficient, defined as serum 25(OH)vitamin D <20 ng/mL. Deficiency was not associated with greater DAS28 (β-0.021 [95% CI -0.22...

To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheumatoid arthritis (RA). This study was conducted as a secondary study of 2 RA clinical trials, GO-BEFORE (development cohort) and GO-FORWARD (validation cohort). Generalized estimating equations were used to evaluate independent cross-sectional associations of component variables (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared...

Dual-energy X-ray absorptiometry (DXA) techniques are limited in childhood chronic kidney disease (CKD) by the confounding effect of short stature and opposing parathyroid hormone effects on trabecular and cortical bone. Peripheral quantitative computed tomography (pQCT) is not subject to these limitations. Lumbar spine (LS) and whole-body (WB) DXA and tibia pQCT scans were obtained in 88 stage 4-5 CKD and >650 healthy participants, ages 5-21 years. Sex- and race-specific Z-scores were generated for bone mineral density (BMD) and bone mineral content (BMC) by DXA, relative to age and adjusted for height Z-score (LS-BMD-Z and WB-BMC-Z), and compared to pQCT Z-scores for trabecular BMD (TrabBMD-Z) for age and cortical BMC (CortBMC-Z) for age and tibia length. LS-BMD-Z [0.50 (95% C.I. 0.28, 0.73), p<0.0001] and TrabBMD-Z [0.53 (0.27, 0.79), p<0.0001] were greater in CKD, and WB-BMC-Z [-0.36 (-0.53, -0.19), p<0.0001] and CortBMC-Z [-0.48 (-0.70, -0.27), p<0.0001] were lower, compared to reference participants. Z-scores were correlated at trabecular (LS-BMD-Z and TrabBMD-Z: R=0.36) and cortical (WB-BMC-Z and CortBMC-Z: R=0.64) sites in CKD; similar to correlations in reference participants. Lumbar spine and whole-body DXA suggested greater trabecular BMD and lower cortical BMC in CKD, consistent with pQCT results; however, correlations were modest. Studies are needed to identify methods that predict fracture in childhood CKD.

Childhood obesity is associated with biologic and behavioral characteristics that may impact bone mineral density (BMD) and structure. The objective was to determine the association between obesity and bone outcomes, independent of sexual and skeletal maturity, muscle area and strength, physical activity, calcium intake, biomarkers of inflammation, and vitamin D status. Tibia and radius peripheral quantitative CT scans were obtained in 91 obese (BMI>97th percentile) and 51 non-obese adolescents (BMI>5th and <85th percentiles). Results were converted to sex- and race-specific Z-scores relative to age. Cortical structure, muscle area and muscle strength (by dynamometry) Z-scores were further adjusted for bone length. Obese participants had greater height Z-scores (p<0.001), and advanced skeletal maturity (p<0.0001), compared with non-obese participants. Tibia cortical section modulus and calf muscle area Z-scores were greater in obese participants (1.07 and 1.63, respectively, both p<0.0001). Tibia and radius trabecular and cortical volumetric BMD did not differ significantly between groups. Calf muscle area and strength Z-scores, advanced skeletal maturity, and physical activity (by accelerometry) were positively associated with tibia cortical section modulus Z-scores (all p<0.01). Adjustment for muscle area Z-score attenuated differences in tibia section modulus Z-scores between obese and non-obese participants from 1.07 to 0.28. After multivariate adjustment for greater calf muscle area and strength Z-scores, advanced maturity, and less moderate to vigorous physical activity, tibia section modulus Z-scores were 0.32 (95% CI -0.18, 0.43, p=0.06) greater in obese, vs. non-obese participants. Radius cortical section modulus Z-scores were 0.45 greater (p=0.08) in obese vs. non-obese participants; this difference was attenuated to 0.14 with adjustment for advanced maturity. These findings suggest that greater tibia cortical section modulus in obese adolescents is attributable to advanced skeletal maturation and greater muscle area and strength, while less moderate to vigorous physical activities offset the positive effects of these covariates. The impact of obesity on cortical structure was greater at weight bearing sites.

BACKGROUND.The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic settings. Schools are ideal settings for population-based interventions to address obesity. OBJECTIVE.The purpose of this work was to examine the effects of a multicomponent, School Nutrition Policy Initiative on the prevention of overweight (85.0th to 94.9th percentile) and obesity (95.0th percentile)

Greater body mass index (BMI) has been associated with less radiographic progression in rheumatoid arthritis (RA). We evaluated the association between BMI and joint damage progression as measured by X-ray and MRI. 1068 subjects with RA from two clinical trials of golimumab (GO-BEFORE and GO-FORWARD) had radiographs performed at weeks 0, 52 and 104 and evaluated using the van der Heijde-Sharp (vdHS) scoring system. Contrast-enhanced MRIs of the dominant wrist and hand were obtained at weeks 0, 12, 24, 52 and 104. Multivariable logistic regression evaluated the risk of radiographic progression for each BMI category (<25, 25-30, >30 kg/m(2)). Within GO-BEFORE, piecewise, robust generalised estimating equations marginal models assessed the probability of MRI erosion progression for each BMI category. Multivariable linear regression models assessed baseline associations between BMI and bone oedema (a precursor of bone erosion). Higher BMI category was associated with a lower proba...

Cardiovascular conditions rank sixth in causes of death in 1- to 19-year-olds. Our study is the first analysis of the cardiovascular death data set from the National Center for the Review and Prevention of Child Deaths, which provides the only systematic collection of cardiovascular deaths in children. We developed an analytical data set from the National Center for the Review and Prevention of Child Deaths database for cardiovascular deaths in children 0 to 21 years old, reviewing 1,098 cases from 2005 to 2009 in 16 states who agreed to participate. Cardiovascular cases were aged 4.8 ± 6.6 years; 55.3%, ≤1 year; 24.6%, ≥10 years; male, 58%; white, 70.5%; black, 22.3%; Hispanic, 19.5%. Prior conditions were present in 48.5%: congenital heart disease, 23%; cardiomyopathies, 4.6%; arrhythmia, 1.7%; and congestive heart failure, 1.6%. Deaths occurred most frequently in urban settings, 49.2%; and in the hospital, 40.4%; home, 26.1%; or at school/work/sports, 4.8%. Emergency medical services were not evenly distributed with differences by age, race, ethnicity, and area. Autopsies (40.4%) occurred more often in those >10 years old (odds ratio [OR] 2.9), blacks (OR 1.6), or in those who died at school/work/sports (OR 3.9). The most common cardiovascular causes of death included congenital heart disease, 40.8%; arrhythmias, 27.1%; cardiomyopathy, 11.8%; myocarditis, 4.6%; congestive heart failure, 3.6%; and coronary artery anomalies, 2.2%. Our study identified differences in causes and frequencies of cardiovascular deaths by age, race, and ethnicity. Prevention of death may be impacted by knowledge of prior conditions, emergency plans, automated external defibrillator programs, bystander cardiopulmonary resuscitation education, and by a registry for all cardiovascular deaths in children.

The only systematic collection of cardiovascular (CV) deaths in children resides in the database derived from the Case Reporting System of the National Center for the Review and Prevention of Child Deaths (NCRPCD). We describe the process used to develop an analytical data set to inform our understanding of CV deaths in children from this database. Twenty-five states reporting natural CV deaths during 2005 to 2009 were contacted. Sixteen states agreed to participate. Cases experienced a natural CV death and were 0 to 21 years. Challenges to building a final analytical data set were identified and included reclassification, recategorization, and the development of new variables from existing data, including an algorithm to identify sudden cardiac deaths. The final data set included 1,098 cases. Missing data comprised a mean of 41.7% for most key variables. Cardiovascular cases were aged 4.8 ± 6.6 years; 55.3%, ≤1 year, 24.6%, ≥10 years; male, 58%; white, 70.5%; black, 22.3%; and Hispanic, 19.5%. This manuscript provides the first description of the natural CV death data set from the NCRPCD. We identify potential beneficial changes in the NCRPCD Case Reporting System and review process. Analysis of these data will help determine characteristics of CV deaths and allow the assessment of risk factors that can be used to prevent CV death in the young. The rate of CV death can be lowered using knowledge of associations that can be gleaned from this robust database. Best practices for prevention hold promise for a future with fewer deaths that will need to be reviewed.

Electrographic seizures are common in encephalopathic critically ill children, but identification requires continuous EEG monitoring (CEEG). Development of a seizure prediction model would enable more efficient use of limited CEEG resources. We aimed to develop and validate a seizure prediction model for use among encephalopathic critically ill children. We developed a seizure prediction model using a retrospectively acquired multi-center database of children with acute encephalopathy without an epilepsy diagnosis, who underwent clinically indicated CEEG. We performed model validation using a separate prospectively acquired single center database. Predictor variables were chosen to be readily available to clinicians prior to the onset of CEEG and included: age, etiology category, clinical seizures prior to CEEG, initial EEG background category, and inter-ictal discharge category. The model has fair to good discrimination ability and overall performance. At the optimal cut-off point in the validation dataset, the model has a sensitivity of 59% and a specificity of 81%. Varied cut-off points could be chosen to optimize sensitivity or specificity depending on available CEEG resources. Despite inherent variability between centers, a model developed using multi-center CEEG data and few readily available variables could guide the use of limited CEEG resources when applied at a single center. Depending on CEEG resources, centers could choose lower cut-off points to maximize identification of all patients with seizures (but with more patients monitored) or higher cut-off points to reduce resource utilization by reducing monitoring of lower risk patients (but with failure to identify some patients with seizures).

Measures of muscle mass or size are often used as surrogates of forces acting on bone. However, chronic diseases may be associated with abnormal muscle force relative to muscle size. The muscle-bone unit was examined in 64 children and adolescents with new-onset Crohn's disease (CD), 54 with chronic kidney disease (CKD), 51 treated with glucocorticoids for nephrotic syndrome (NS), and 264 healthy controls. Muscle torque was assessed by isometric ankle dynamometry. Calf muscle cross-sectional area (CSA) and tibia cortical section modulus (Zp) were assessed by quantitative CT. Log-linear regression was used to determine the relations among muscle CSA, muscle torque, and Zp, adjusted for tibia length, age, Tanner stage, sex, and race. Muscle CSA and muscle torque-relative-to-muscle CSA were significantly lower than controls in advanced CKD (CSA -8.7%, p = 0.01; torque -22.9%, p < 0.001) and moderate-to-severe CD (CSA -14.1%, p < 0.001; torque -7.6%, p = 0.05), but not in NS. Zp was 11.5% lower in advanced CKD (p = 0.005) compared to controls, and this deficit was attenuated to 6.7% (p = 0.05) with adjustment for muscle CSA. With additional adjustment for muscle torque and body weight, Zp was 5.9% lower and the difference with controls was no longer significant (p = 0.09). In participants with moderate-to-severe CD, Zp was 6.8% greater than predicted (p = 0.01) given muscle CSA and torque deficits (R(2)  = 0.92), likely due to acute muscle loss in newly-diagnosed patients. Zp did not differ in NS, compared with controls. In conclusion, muscle torque relative to muscle CSA was significantly lower in CKD and CD, compared with controls, and was independently associated with Zp. Future studies are needed to determine if abnormal muscle strength contributes to progressive bone deficits in chronic disease, independent of muscle area. © 2014 American Society for Bone and Mineral Research.

The GEEQBOX toolbox analyzes correlated data via the method of generalized estimating equations (GEE) and quasi-least squares (QLS), an approach based on GEE that overcomes some limitations of GEE that have been noted in the literature. GEEQBOX is currently able to handle correlated data that follows a normal, Bernoulli or Poisson distribution, and that is assumed to have an AR(1), Markov, tri-diagonal, equicorrelated, unstructured or working independence correlation structure. This toolbox is for use with MATLAB.

Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. We linked United Network for Organ Sharing registry data about posttransplantation survival with pretransplantation functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from June 1, 2000 to May 31, 2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for 3-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. The cohort comprised 10,875 kidney transplant recipients with a mean age of 50 years; 14% were ≥65. Differences in 3-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients ≥65 years. In multivariable Cox regression, worse PF was associated with higher mortality (hazard ratio, 1.66 for lowest vs. highest PF quartiles; P<0.001). Interactions between PF and age were nonsignificant. We estimated that 11% fewer deaths would occur if kidney transplant recipients with the lowest functional status experienced modest improvements in function. Across a wide age range, functional status was an independent predictor of posttransplantation survival. Functional status assessment may be a useful tool with which to counsel patients about posttransplantation outcomes.

This note implements an unstructured decaying product matrix via the quasi-least squares approach for estimation of the correlation parameters in the framework of generalized estimating equations. The structure we consider is fairly general without requiring the large number of parameters that are involved in a fully unstructured matrix. It is straightforward to show that the quasi-least squares estimators of the correlation parameters yield feasible values for the unstructured decaying product structure. Furthermore, subject to conditions that are easily checked, the quasi-least squares estimators are valid for longitudinal Bernoulli data. We demonstrate implementation of the structure in a longitudinal clinical trial with both a continuous and binary outcome variable.

This paper is motivated by a study of physical activity participation habits in African American women with three potential sources of correlation among study outcomes, according to method of assessment, timing of measurement, and intensity of physical activity. To adjust for the multiple sources of correlation in this study, we implement an approach based on generalized estimating equations that models association via a patterned correlation matrix. We present a general algorithm that is relatively straightforward to program, an analysis of our physical activity study, and some asymptotic relative efficiency comparisons between correctly specifying the correlation structure vs ignoring two sources of correlation in the analysis of data from this study. The efficiency comparisons demonstrate that correctly modeling the correlation structure can prevent substantial losses in efficiency in estimation of the regression parameter.

Existing methods for power analysis for longitudinal study designs are limited in that they do not adequately address random missing data patterns. Although the pattern of missing data can be assessed during data analysis, it is unknown during the design phase of a study. The random nature of the missing data pattern adds another layer of complexity in addressing missing data for power analysis. In this paper, we model the occurrence of missing data with a two-state, first-order Markov process and integrate the modelling information into the power function to account for random missing data patterns. The Markov model is easily specified to accommodate different anticipated missing data processes. We develop this approach for the two most popular longitudinal models: the generalized estimating equations (GEE) and the linear mixed-effects model under the missing completely at random (MCAR) assumption. For GEE, we also limit our consideration to the working independence correlation model. The proposed methodology is illustrated with numerous examples that are motivated by real study designs.

It has been recognized that in addition to being overweight, abnormal fat distribution may be associated with the etiology of metabolic syndrome. Asian people are more prone to develop visceral obesity than people in western countries. The present study was initiated to evaluate the relationship between visceral obesity and renal damage in Chinese obese people. As measured by computed tomography, the areas of visceral fat were compared between 30 patients with biopsy-proven obesity-related glomerulopathy (ORG) and 20 obese volunteer controls that were free of renal diseases. The two groups were matched for age and sex. It was found that the areas of visceral fat were markedly increased in patients with ORG, while body mass indexes were similar in the two groups. Patients with ORG also showed higher levels of total cholesterol and a higher degree of insulin resistance than the controls. Multiple logistic regression analysis revealed that visceral obesity was significantly associated with the prevalence of ORG (OR 1.136; 95%CI, 1.106-1.166; P=0.003). Interestingly, proteinuria level was related directly with waist circumference, visceral obesity and levels of total cholesterol, fasting glucose, insulin and HOMA-IR ( P<0.05). Moreover, only HOMA-IR was independently associated with proteinuria level in stepwise linear regression ( R=0.641; P=0.001). The present study illustrated the positive association between visceral obesity and ORG and between insulin resistance and proteinuria level in Chinese obese subjects.

To develop an improved model for the prediction of bacteremia in young febrile children. A retrospective review was performed on patients 3 to 36 months of age seen in a children's hospital emergency department between December 1995 and September 1997 who had a complete blood count and blood culture ordered as part of their regular care. Exclusion criteria included current use of antibiotics or any immunodeficient state. Clinical and laboratory parameters reviewed included age, gender, race, weight, temperature, presence of focal bacterial infection, white blood cell count (WBC), polymorphonuclear cell count (PMN), band count, and absolute neutrophil count (ANC). Logistic regression analyses were used to identify factors associated with bacteremia, defined as growth of a pathogen in a blood culture. The model that was developed was then validated on a second dataset consisting of febrile patients 3 to 36 months of age collected from a second children's hospital (validation set). There were 633 patients in the derivation set (46 bacteremic) and 9465 patients in the validation set (149 bacteremic). The mean age of patients in the derivation and validation sets were 15.8 months (95% confidence interval [CI]: 15.2-16.5) and 16.6 months (95% CI: 16.5-16.8), respectively; the mean temperatures were 39.1 degrees C (95% CI: 39. 0-39.2) and 39.8 degrees C (95% CI: 39.7-39.8); 56% were male in the derivation set and 55% male in the validation set. Predictors of bacteremia identified by logistic regression included ANC, WBC, PMN, temperature, and gender. Receiver operator characteristic (ROC) analysis showed similar performance of ANC and WBC as predictors of bacteremia. When placed into a multivariate logistic regression model, band count was not significantly associated with bacteremia. Information regarding focal infection was available for 572 patients in the derivation set. The percentage of patients diagnosed with bacteremia with a focal bacterial infection was not significantly different from the percentage who had bacteremia without a focal bacterial infection (16/200 vs 30/372). Based on this dataset, a logistic regression formula was developed that could be used to develop a unique risk value for each patient based on temperature, gender, and ANC. When the final model was applied to the validation set, the area under the ROC curve (AUC) constructed from these data indicated that the model retained good predictive value (AUC for the derivation vs validation data =.8348 vs 0.8221, respectively). Use of the formulas derived here allows the clinician to estimate a child's risk for bacteremia based on temperature, ANC, and gender. This approach offers a useful alternative to predictions based on fever and WBC alone.bacteremia, detection, white blood cell.

Objectives: To examine the incidence of symptomatic and asymptomatic ETEC infection among low-income Mexican children< 24 months of age and protection by breastfeeding (BF). Methods: From 4/88 to 12/91, 317 infants residing in the SW outskirts of Mexico City ...

Extreme prematurity is a risk factor for both candidemia and threshold retinopathy of prematurity (ROP) and may confound the reported association between these conditions. To determine if candidemia is an independent risk factor for threshold ROP. A cohort study was conducted of infants weighing </=1000 g at birth using a prospectively maintained neonatal database. The study included infants admitted to the neonatal intensive care unit at </=3 days of age between January 1, 1993 and December 31, 1997. We excluded infants not screened for ROP because they died, were discharged, or transferred. Threshold ROP (ie, requiring ablative therapy within 72 hours of diagnosis) was defined by the criteria of the American Academy of Pediatrics Section on Ophthalmology ROP subcommittee. Candidemia was defined as Candida species growth from at least 1 blood culture. Cox proportional hazards regression was used to determine independent risk factors for threshold ROP. Six hundred fourteen infants weighing </=1000 g at birth, of which 165 were excluded: 120 died before ROP screening, 40 were admitted >3 days of age, and 5 were discharged or transferred before ROP screening. A total of 449 infants were included in the study; 58 (13%) developed threshold ROP. Candidemia occurred in 58 (13%) infants before developing the worst stage of ROP. Candidemia occurred in 27 of 73 (37%) at 23 to 24 weeks' gestational age (GA), 25 of 197 (13%) at 25 to 26 weeks' GA, and 6 of 129 (5%) at 27 to 28 weeks' GA, 0 of 50 >28 weeks' GA. Similarly, threshold ROP occurred in 25 of 73 (34%) at 23 to 24 weeks' GA, 26 of 197 (13%) at 25 to 26 weeks' GA, and 6 of 129 (5%) at 27 to 28 weeks' GA, and 1 of 50 (2%) >28 weeks' GA. Threshold ROP developed in 19 of 58 (33%) infants with a history of candidemia and 39 of 391 (10%) without candidemia. Proportional hazards analysis indicated that GA in weeks (hazard ratio =.75; 95% confidence interval [CI]:. 61,.93) and non-black ethnicity (hazard ratio = 1.8; 95% CI: 1.05, 3. 08) were significantly associated with threshold ROP. After controlling for GA and other factors, candidemia did not remain significantly associated with threshold ROP (hazard ratio = 1.6; 95% CI:.89, 2.89). Candidemia may not be an independent risk factor for threshold ROP in extremely low birth weight infants. The magnitude of the previously reported association between candidemia and threshold ROP (more than fivefold) is unlikely and much of the clinically observed association appears to be mediated by gestational age.

Vitamin D-binding protein (DBP) and catabolism have not been examined in the clinical setting of childhood chronic kidney disease (CKD). The concentrations of serum vitamin D {25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], 24,25-dihydroxyvitamin D [24,25(OH)(2)D]}, DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) were measured in 148 participants with CKD stages 2-5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D concentrations were calculated using total 25(OH)D, albumin, and DBP concentrations. The concentrations of all vitamin D metabolites were lower with more advanced CKD (p < 0.001) and glomerular diagnoses (p ≤ 0.002). Among non-dialysis participants, DBP was lower in FSGS versus other diagnoses (FSGS-dialysis interaction p = 0.02). Winter season, older age, FSGS and GN, and higher FGF23 concentrations were independently associated with lower concentrations of free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)(2)D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D and higher iPTH concentrations, black race, and greater CKD severity were independently associated with lower levels of 24,25(OH)(2)D, while higher FGF23 concentrations and GN were associated with higher levels of 24,25(OH)(2)D. Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease.

The objective of this work was to determine the prevalence of obesity, defined as BMI >95th percentile, in children treated with glucocorticoids for steroid-sensitive nephrotic syndrome (SSNS), and to identify risk factors for the development for glucocorticoid-induced obesity. The experimental design involved a cross-sectional study of 96 individuals (4 to 21 yrs) treated with glucocorticoids for SSNS and 186 healthy reference subjects. Logistic regression was used to generate odds ratios for obesity. Glucocorticoid exposure was classified as recent in the 54 subjects treated with glucocorticoids in the prior six months, and remote in the remaining 42 subjects. Recent exposure was associated with significantly increased odds of obesity [odds ratio (95% CI): 26.14 (7.54, 90.66)] in non-blacks only. Each one-unit increase in maternal BMI was associated with a 35% increase in the odds of obesity in recent SSNS subjects (p=0.003). The effect of maternal BMI on the odds of obesity was significantly greater in recent SSNS subjects than in reference subjects (test for interaction p=0.038). The odds of obesity were also significantly increased [odds ratio 5.22 (1.77, 15.41), p=0.003] in all subjects with remote glucocorticoid exposure (black and non-black). These results indicate that non-black race and increased maternal BMI are risk factors for glucocorticoid-induced obesity in subjects with recent exposure.

Obesity and hypertension frequently complicate renal transplantation (RTxp). The objective was to assess relations among obesity, hypertension, and glucocorticoids in pediatric RTxp recipients. A retrospective cohort study was carried out in 141 RTxp recipients, 2-21 years of age, with >or=12 months of follow-up. Body mass index Z-score (BMI-Z), systolic and diastolic blood pressure Z-scores (SBP-Z and DBP-Z), and medications at 1, 3, 6, and 12 months and annually thereafter were recorded. Quasi-least squares regression analysis was used. The prevalence of obesity (BMI>or=95th percentile) increased from 13% at baseline to >30% from 3 months onward. Greater glucocorticoid exposure (mg/kg/day) was associated with greater increases in BMI-Z (p<0.001). This association was greater in males, younger recipients, and those with lower baseline BMI-Z (all interactions p<0.02). The prevalence of systolic hypertension (SBP>or=95th percentile) was 73% at 1 month and >or=40% at all follow-up visits. Greater glucocorticoid exposure (p<0.001) and increases in BMI-Z (p=0.005) were independent determinants of SBP-Z over time. Cyclosporine (versus tacrolimus) was independently associated with greater SBP-Z and DBP-Z (p=0.001). Sustained obesity and hypertension frequently complicated pediatric RTxp. Obesity was an independent determinant of systolic hypertension. Strategies are needed to prevent obesity and its impact on hypertension, cardiovascular disease, and allograft survival.

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)(2)D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)(2)D levels.

To develop and validate predictive models to determine the need for hospitalization in children treated for acute asthma in the emergency department (ED). Prospective cohort study of children aged 2 years and older treated at 2 pediatric EDs for acute asthma. The primary outcome was successful ED discharge, defined as actual discharge from the ED and no readmission for asthma within 7 days, versus need for extended care. Among those defined as requiring extended care, a secondary outcome of inpatient care (>24 hours) or short-stay care (<24 hours) was defined. Logistic regression and recursive partitioning were used to create predictive models based on historical and clinical data from the ED visit. Models were developed with data from 1 ED and validated in the other. There were 852 subjects in the derivation group and 369 in the validation group. A model including clinical score (Pediatric Asthma Severity Score) and number of albuterol treatments in the ED distinguished successful discharge from need for extended care with an area under the receiver-operator characteristic curve of 0.89 (95% confidence interval [CI], 0.87-0.92) in the derivation group and 0.92 (95% CI, 0.89-0.95) in the validation group. Using a score of 5 or more as a cutoff, the likelihood ratio positive was 5.2 (95% CI, 4.2-6.5), and the likelihood ratio negative was 0.22 (95% CI, 0.17-0.28). Among those predicted to need extended care, a classification tree using number of treatments in the ED, clinical score at end of ED treatment, and initial pulse oximetry correctly classified 63% (95% CI, 56-70) of the derivation group as short stay or inpatient, and 62% (95% CI, 55-68) of the validation group. Successful discharge from the ED for children with acute asthma can be predicted accurately using a simple clinical model, potentially improving disposition decisions. However, predicting correct placement of patients requiring extended care is problematic.