Self-Management and Transition Readiness Assessment: Development, Reliability, and Factor Structure of the STARx Questionnaire.

INTRODUCTION: The Self-Management and Transition to Adulthood with Rx=Treatment (STARx) Questionnaire was developed to collect information on self-management and health care transition (HCT) skills, via self-report, in a broad population of adolescents and young adults (AYAs) with chronic conditions. METHODS: Over several iterations, the STARx questionnaire was created with AYA, family, and health provider input. The development and pilot testing of the STARx Questionnaire took place with the assistance of 1219 AYAs with different chronic health conditions, in multiple institutions and settings over three phases: item development, pilot testing, reliability and factor structuring. RESULTS: The three development phases resulted in a final version of the STARx Questionnaire. The exploratory factor analysis of the third version of the 18-item STARx identified six factors that accounted for about 65% of the variance: Medication management, Provider communication, Engagement during appointments, Disease knowledge, Adult health responsibilities, and Resource utilization. Reliability estimates revealed good internal consistency and temporal stability, with the alpha coefficient for the overall scale being .80. The STARx was developmentally sensitive, with older patients scoring significantly higher on nearly every factor than younger patients. CONCLUSION: The STARx Questionnaire is a reliable, self-report tool with adequate internal consistency, temporal stability, and a strong, multidimensional factor structure. It provides another assessment strategy to measure self-management and transition skills in AYAs with chronic conditions.

Dietary modifications alone do not improve bone mineral density in children with idiopathic hypercalciuria.

Prior cross-sectional studies have demonstrated an association between hypercalciuria and low bone mineral density (BMD) in children and adults. However, the natural history of BMD in children with hypercalciuria and its response to therapy has not been evaluated. The objective of this retrospective study was to determine the change over time in lumbar (L1 - L4) BMD Z-score measured on sequential DXA scans in 19 children with hypercalciuria treated with dietary recommendations without (n = 12, Group A) and with citrate (n = 7, Group B). The mean lumbar bone density Z-score/year decreased in Group A (-0.11 ±/0.41) indicating that children with hypercalciuria lose L1 - L4 BMD over time. In contrast, the L1 - L4 BMD Zscore/ year increased in Group B (0.19 ± 0.38) suggesting that pharmacologic therapy may reverse this trend. Similarly 75% of patients in Group A, but only 29% patients in Group B had a decrease in L1 - L4 BMD. There was a definite, although not significant, trend towards improved mean bone mineral density Z-score per year and a lower percentage of patients with a decreased Z-score in hypercalciuric children treated with potassium citrate. Our findings suggest the possibility that dietary recommendations alone is not adequate as the bone mineral density of children with hypercalciuria will decrease over time, potentially increasing the risk for osteoporosis as an adult.

Improving Resident Self-Efficacy in Tracheostomy Management Using a Novel Curriculum.

Introduction: Patients receiving pediatric tracheostomy have significant risk for mortality due to compromised airway. Timely management of airway emergencies in children with tracheostomies is an important clinical skill for pediatricians. We developed this curriculum to improve residents' self-efficacy with tracheostomy management. Methods: We collected baseline data on 67 residents from two hospitals while creating a blended curriculum with video-based instruction on routine tracheostomy change and team management of tracheostomy emergency. Forty residents enrolled in the curriculum. During an ICU rotation, they received face-to-face instruction on routine tracheostomy change in small groups, followed by assessment of managing a tracheostomy emergency during a simulation. A video completed prior to the simulation took 9 minutes, the routine tracheostomy change didactic session took 15 minutes, and the simulation instruction was completed in 10-15 minutes. We collected feedback on the effectiveness of the curriculum from the participants. Results: All 107 residents from the baseline and intervention groups completed the self-efficacy survey. The intervention group had significantly higher changes in scores across all self-efficacy domains than the baseline group. On the curriculum feedback survey, residents rated the curriculum very highly, between 4.4 and 4.8 on a 5-point Likert scale. Discussion: Our blended curriculum increased learners' self-efficacy and promoted learner competence in tracheostomy management. Residents scored more than 80% across all aspects of simulation assessment and reported higher self-efficacy scores following our curricular intervention.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

PURPOSE: Well-functioning vascular access is essential for the provision of adequate CRRT. However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. METHODS: Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. RESULTS: Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). CONCLUSIONS: Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

Preparedness of pediatric residents for fellowship: a survey of US neonatal-perinatal fellowship program directors.

OBJECTIVE: To evaluate the preparedness of pediatric residents entering accredited neonatal-perinatal medicine (NPM) fellowships in the United States. STUDY DESIGN: A multi-domain, validated survey was distributed to Program Directors (PDs) of US NPM fellowship programs. The 47-item survey explored 5 domains: professionalism, independent practice, psychomotor ability, clinical evaluation, and academia. A systematic, qualitative analysis on free-text comments was also performed. RESULTS: Sixty-one PDs completed the survey, for a response rate of 62% (61/98). For entering fellows, PDs assessed performance in professionalism positively, including 76% as communicating effectively with parents and 90% treating residents/house-staff with respect. In contrast, most PDs rated performance in psychomotor abilities negatively, including 59% and 79% as deficient in bag-and-mask ventilation and neonatal endotracheal intubation, respectively. Although 62% of PDs assessed entering fellows positively for genuine interest in academic projects, fewer than 10% responded positively that entering fellows understood research protocol design, basic statistics, or were capable of writing a cohesive manuscript well. Thematic clustering of qualitative data revealed deficits in psychomotor ability and academia/scholarship. CONCLUSIONS: On the basis of the perspective of front line educators, graduating pediatric residents are underprepared for subspecialty fellowship training in NPM. To provide the best preparation for pediatric graduates who pursue advanced training, changes to residency education to address deficiencies in these important competencies are warranted.

Combined nephrotoxic effects of cyclosporine and endotoxin.

This study presents experimental evidence that cyclosporine (CsA) potentiates the nephrotoxicity of endotoxin. This study was motivated by clinical observations in 4 cyclosporine (CsA)-treated renal allograft recipients who developed severe, and sometimes irreversible, nephrotoxicity after infections. CsA or vehicle was administered intramuscularly to rabbits for 5 days, and subsequently both groups of animals received one dose of endotoxin intravenously. Compared with controls, CsA-treated animals demonstrated significantly higher elevations of blood urea nitrogen and serum creatinine 24 hr after endotoxin. By contrast, both groups of animals developed similar degrees of thrombocytopenia. Histologic evaluation of kidney tissues 24 hr after endotoxin revealed significantly greater tubular toxicity and a higher glomerular polymorphonuclear leukocyte (PMN) infiltration in CsA-treated animals. Semiquantitative scores of tubular damage correlated directly with the mean number of PMN/glomeruli in both groups of animals. Immunofluorescent microscopy of kidney tissues was negative for fibrinogen and for complement deposition in both CsA and control groups. We conclude that CsA enhances endotoxin nephrotoxicity in rabbits. This effect does not appear to be mediated by activation of coagulation factors. However, a role for PMN is suggested. CsA should be used with caution in patients with deteriorating renal function who are suspected of having severe bacterial infections.

Cyclosporine nephrotoxicity in spontaneously hypertensive rats.

In the present study, we investigated the combined, nephrotoxic effects of cyclosporine (CsA) and hypertension in young, spontaneously hypertensive rats (SHR). After 4 weeks of CsA therapy, SHR, compared with oil-treated SHR, showed an acceleration in the development of hypertension, mild renal insufficiency, and the accumulation of periodic-acid-Schiff-positive (PAS [+]) material in periglomerular arterioles. By electron microscopy, PAS(+) material was composed of intracytoplasmic inclusion bodies consistent with the accumulation of renin granules. This finding was demonstrated in SHR after 4 weeks of CsA therapy but not after 8 weeks of therapy. By contrast, CsA had no significant effect on blood pressure in Wistar-Kyoto rats, a normo-tensive control. To investigate the effect of unilateral nephrectomy (UNx) on the development of renal histopathologic changes in this model, SHR were subjected to uninephrectomy and CsA or oil therapy. UNx accelerated the development of hypertension in all SHR groups. SHR subjected to UNx demonstrated no renal histopathologic changes after CsA or oil treatment. In conclusion, CsA accelerates the development of hypertension in SHR, and this effect is probably renin-mediated. The combination of UNx and CsA therapy in the SHR does not result in significant renal histologic damage.

Diabetic nephropathy in an aerobically trained rat model of diabetes.

The purpose of this study was to determine the effects of aerobic training on indices of glycemic control, blood pressure, serum lipids, and diabetic nephropathy (DN) in an animal model of insulin deficient diabetes mellitus. Thirty-four male Sprague-Dawley rats made diabetic with streptozocin were randomly assigned to a trained group or a sedentary group. Fifteen sedentary-nondiabetic rats served as a control group. The animals were trained on a treadmill at 18 m.min-1, 8 degrees incline for 120 min.d-1, 5 d.wk-1. Blood and 24 h urine collections were obtained at various intervals throughout the study. At 21 wk of age systolic blood pressure was measured and kidney tissue was obtained for light and electron microscopy. Analysis of variance was used to detect differences among the groups (P < or = 0.05). The diabetes produced in this investigation resulted in hyperglycemia, increased urine albumin and total protein excretion, elevated systolic blood pressure, increased fractional volume of the mesangium, and widening of the glomerular basement membrane in the sedentary-diabetic animals. Aerobic training significantly reduced the increase in fractional volume of the mesangium and fructosamine. Most importantly, aerobic training did not augment the renal damage seen in DN.

Evaluation of hematuria, proteinuria, and hypertension in adolescents.

Signs or symptoms of renal disease in adolescents deserve prompt attention and appropriate evaluation. Adolescents are susceptible to a variety of urinary tract disorders. The key issue in the evaluation of hematuria or proteinuria in adolescents is the existence of concomitant signs of renal disease. For isolated hematuria or proteinuria, demonstration of persistence and a reasoned evaluation are in order. Hypertension in adolescents must be carefully documented and, when present, considered seriously. The fact that most teens with persistent elevated blood pressures have essential hypertension is still a great concern because for most of these adolescents the hypertension will be lifelong and, if left untreated, can be associated with significant morbidity and mortality in the adult years.

Aerobic training and diabetic nephropathy in the obese Zucker rat.

The effects of aerobic exercise training on diabetes control and the development of renal microvascular disease were studied in the obese Zucker rat, an animal model of noninsulin dependent diabetes mellitus (NIDDM). Training consisted of 12 weeks of treadmill running, beginning at six weeks of age. Eight trained obese Zucker rats were compared to 15 obese sedentary controls and to 22 sedentary lean nondiseased littermates. Fasting blood glucose, percent of glycated hemoglobin, serum insulin, serum total cholesterol, body weight and kidney weight, creatinine clearance, urine total protein excretion, urine albumin excretion, and morphometric analyses of cortical glomeruli by light and electron microscopy were performed to evaluate metabolic control, renal function, and structure. Training was associated with less albuminuria, less mesangial volume expansion, and less glomerular basement membrane thickening compared to obese sedentary NIDDM animals. These results suggest that exercise training reduces the glomerular ultrastructural lesions and attenuates the albumin excretion rate in this rat model of obesity-related diabetes.

Anionic charge sites in the kidney: comparison of two diabetic rat models.

The distribution and appearance of anionic charge sides (ACS) in the glomerular basement membrane (GBM) and mesangium were studied in two different animal models of diabetes mellitus (DM), the obese Zucker rat as an animal model of type 2 diabetes mellitus (DM) and streptozocin-induced Sprague-Dawley rat as an animal model of type 1 DM. Four obese Zucker rats (ZR) and four Sprague-Dawley rats were analyzed for the following parameters: number of ACS per length of lamina rara externa (LRE), (ACS/LRE); number of ACE per length of lamina rara interna (LRI) (ACS/LRI); percent of mesangial matrix as ACS (%MMACS); percent of LRE as ACS (%LREACS); percent of LRI as ACS (%LRIACS); length of ACS in LRI (LACSLRI); length of ACS in LRE (LACSLRE); width of ACS in LRI (WACSLRI); width of ACS in the LRE (WACSLRE); area of ACS in the LRI (AACSLRI); and the area of ACS in the LRE (AACSLRE). Statistical analyses include a one-way analysis of variance (ANOVA), Pearson's correlation coefficient, and stepwise multiple regression. This study confirms that a loss of ACS occurs as proteinuria develops in a variety of animal models. The majority of the ACS were more prominently localized, and thus lost form the LRE of the GBM in DN. This study also demonstrated that defined alterations in the glomerular ACS can be identified early in the evolution of DN in both animal models, and that the similarity of the changes in the ACS suggest that a common pathophysiologic mechanism induced the changes in both animal models.

Infarction of the choledochus, liver, gallbladder, and pancreas: a unique complication of the hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is associated with multiple nonrenal manifestations. A unique case is described of a 3-year-old boy who presented with a classic diarrheal prodrome followed by massive necrosis of the biliary tree and common bile duct, pancreas, and the left lobe of his liver. This complication of HUS has not been reported in the English-language literature.

The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: design, development and data assessed.

Many issues plague the pediatric ARF outcome literature, which include data only from single center sources, a relative lack of prospective study, mixture within studies of renal replacement therapy modality without stratification and inconsistent use of methods to control for patient illness severity in outcome analysis. Since January 2001, the Prospective Pediatric CRRT (ppCRRT) Registry Group has been collecting data from multiple United States pediatric centers to obtain demographic data regarding pediatric patients who receive CRRT, assess the effect of different CRRT prescriptions on circuit function and evaluate the impact of clinical variables on patient outcome. The aim of the current paper is to describe the ppCRRT Registry design, review the decision process and rationale for the options chosen for the ppCRRT format and discuss the analysis plan and future projects envisioned for the ppCRRT Registry.

Role of precipitating and nonprecipitating antibodies in glomerular immune complex formation.

The present study compared directly the ability of precipitating and nonprecipitating antibodies to form and sustain glomerular immune deposits. The antigen phenylated gelatin (DNP-GL) was injected i.v. into rats. DNP-GL is cleared from the circulation rapidly and becomes localized in glomeruli. Two hours later, rats received either precipitating or nonprecipitating mouse monoclonal anti-DNP antibodies. These antibodies were comparable with respect to size, affinity, number of antigen combining sites and isoelectric point. However, in vitro, nonprecipitating antibodies demonstrated a faster dissociation rate from antigen than precipitating antibodies. Control rats received DNP-GL alone or antibody alone. Antibody deposition in glomeruli was quantitated by Computerized Image Analysis (CIA) of immunoperoxidase stained tissue sections and by glomerular radioactive counts in experiments using 125I labelled antibodies. We demonstrated that glomerular uptake of anti-DNP antibody was similar two hours after injection of precipitating and nonprecipitating antibodies. However, six or more hours after injection, significantly less antibody was present in the glomeruli of rats injected with nonprecipitating antibodies. These differences could not be explained by a greater rate of antigen removal from kidney in rats injected with nonprecipitating antibodies. To assess whether nonprecipitating antibodies modify the glomerular binding and retention of precipitating antibody, in a separate series of experiments rats were injected with equal amounts of precipitating and nonprecipitating antibodies. Both types of antibody bound to glomeruli. However, with time glomerular antibody levels paralleled those found in rats injected with nonprecipitating antibody alone. We conclude that the precipitating characteristics of antibodies do not affect their ability to deposit in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental glomerulonephritis induced by antigen that binds to glomerular fibronectin.

In previous studies we demonstrated that antigens with the capacity to bind to the glycoprotein fibronectin (FN), localized in the glomerular mesangium after intravenous (IV) injection. In the present study we sought to determine if the localization of FN-binding antigens in the mesangium is capable of inducing glomerulonephritis. A group of rats were injected IV with the FN-binding antigen phenylated gelatin (DNP-GL) followed 2 hours later by rabbit anti-DNP antibodies. This experimental protocol resulted in the development of a glomerulonephritis characterized by an initial heterologous phase and a late autologous phase. Both phases of the disease were characterized by significant histologic changes, including focal segmental mesangial matrix expansion, inflammatory cell infiltration, and an increase in endothelial and mesangial cells. By immunoperoxidase we demonstrated mesangial deposition of rabbit IgG and rat C3 during the initial heterologous phase and mesangial deposition of rat IgG and C3 during the autologous phase. Significant proteinuria developed during the heterologous phase, but not during the autologous phase of the disease. By contrast, rats injected with DNP-GL alone or anti-DNP antibodies alone did not develop significant histologic glomerular changes or proteinuria. In conclusion, antigens that bind to mesangial FN are capable of inducing glomerulonephritis. This mechanism of localization of antigens in the glomeruli may be relevant to human immune complex (IC)-mediated diseases involving antigens that have the capacity to bind to FN.

Glomerular basement membrane anionic charge site changes early in aminonucleoside nephrosis.

Alterations of glomerular basement membrane (GBM) anionic (charge sites, CSs) in the development of proteinuria in a model of idiopathic nephrotic syndrome in man (puromycin aminonucleoside nephrotic syndrome [PAN] in the rat) were assessed quantitatively and sequentially early after disease induction. GBM CSs (known to consist mainly of heparan sulfate-rich proteoglycans) were stained in vivo and, in a separate group of animals by an in vitro method, with the cationic marker polyethyleneimine (PEI) studied by electron microscopic examination. Four hours after administration of PAN, there was a significant decrease in GBM lamina rara externa CSs: 18 +/- 0.7 versus 22.0 +/- 2.2 per 1000 nm GBM in controls by PEI injection and 17.2 +/- 2.7 versus 21.1 +/- 1.6 per 1000 nm GBM in controls by PEI in vitro staining. This CS alteration coincided with changes in glomerular epithelial cell morphologic characteristics (increased cytoplasmic organelles and rough endoplasmic reticulum) and preceded the detection of foot process broadening (at 24 hours) and increased urinary albuminuria (suggested at 12-24 hours, statistically significant at 36-48 hours). These results suggest that GBM CS-heparan sulfate proteoglycan alterations consisting of either decreased number and/or less anionic charge occur early in PAN and support a role for glomerular epithelial cell maintenance of GBM CS for normal glomerular function.

Complications of intestinal augmentation and substitution cystoplasty.

The content of these papers has been heavily weighted towards reconstructions performed utilizing segments of stomach. This was not done to place a value judgment on this type of reconstruction, rather it helps establish an awareness of: (1) potentially serious metabolic and gastrointestinal complications not previously reported in children and (2) particularly frequent symptomatic disturbances collectively included in the hematuria-dysuria syndrome. Recognition of problems specifically associated with a certain type of intestinal segment, as well as complications generally accompanying any form of intestinal reconstruction, will hopefully provide pediatric urologists and nephrologists with a better understanding of the issues that must be addressed in using these newer surgical techniques and focus attention on the specific indications and contraindications for incorporating intestinal segments into the urinary tract. Although long-term follow-up information still remains sparse, it appears that regular surveillance programs are required and both pediatric nephrologists and urologists need to be part of these programs.

Localization of decay accelerating factor in normal and diseased kidneys.

Decay accelerating factor (DAF) is a cell membrane associated glycoprotein that inhibits C3 activation. In the present study we evaluated the presence of DAF in normal (N = 15) and diseased human kidneys (N = 76). Sections of frozen tissue were stained for DAF by immunoperoxidase, utilizing three mouse monoclonal anti-DAF anti-bodies. In normal kidneys, DAF was localized in the glomerular vascular pole, apparently in the juxtaglomerular apparatus (JGA). All other structures were negative for DAF. By contrast, in diseased kidneys, two types of abnormalities were detected. First, JGA-DAF was significantly decreased and this abnormality correlated with the pathologic diagnosis and with the presence of C3, IgM and/or fibrinogen in the glomeruli. Second, DAF was present in the glomerular mesangium (67%), renal interstitium (68%) and/or blood vessels (38%). The presence of DAF in the mesangium and interstitium of the kidney correlated with each other and correlated with C1q and C3 deposition in the glomerulus. Finally, vascular DAF was significantly more common in patients with electron dense deposits in the glomeruli. In summary, DAF is present in the normal kidney and is located exclusively in the glomerular vascular pole. In diseased kidneys, DAF tends to be lost from the JGA but is often present in glomerular mesangium, interstitium and blood vessels. This pattern is specially prominent in patients demonstrating complement deposition in the glomerulus. We speculate that kidney DAF may play a role in protecting the kidney against the products of complement activation.

Congenital nephrotic syndrome: evolution of medical management and results of renal transplantation.

We analyzed the clinical course, pathologic findings, and results of aggressive medical management and renal transplantation in 41 infants with onset of nephrotic syndrome in the first 3 months of life. All but one infant with congenital onset failed to thrive and had progressive renal insufficiency; 17 were given steroids or cytotoxic drugs or both, without benefit. Severe bacterial infections occurred in 85% of the infants, pyloric stenosis in 12%, gastroesophageal reflux in 8%, and thrombotic events in 10%. All children prior to the era of renal transplantation died before 4 years of age. The last 24 infants received aggressive medical management, which allowed renal transplantation in 17. Two-year patient and graft survival rates were 82% and 71%, respectively. There was no recurrence of the nephrotic syndrome in the children who underwent transplantation. All but one surviving infants has had normal or accelerated growth, although mean height for the group is 3.1 SD below the mean. School and social performance has been normal in 80%. Thus intensive medical therapy combined with renal transplantation offers a very good opportunity for survival with an acceptable quality of life for infants with congenital nephrotic syndrome.

Angiotensin-converting enzyme inhibition partially prevents diabetic organomegaly.

The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.