Nader Shaikh

Identification of Children and Adolescents at Risk for Renal Scarring After a First Urinary Tract Infection: A Meta-analysis With Individual Patient Data

IMPORTANCE No studies have systematically examined the accuracy of clinical, laboratory, and imaging variables in detecting renal scarring in children and adolescents with a first urinary tract infection. OBJECTIVES To identify independent prognostic factors for the development of renal scarring and to combine these factors in prediction models that could be useful in clinical practice. DATA SOURCES MEDLINE and EMBASE. STUDY SELECTION We included patients aged 0 to 18 years with a first urinary tract infection who underwent follow-up renal scanning with technetium Tc 99m succimer at least 5 months later. DATA EXTRACTION AND SYNTHESIS We pooled individual patient data from 9 cohort studies. MAIN OUTCOMES AND MEASURES We examined the association between predictor variables assessed at the time of the first urinary tract infection and the development of renal scarring. Renal scarring was defined by the presence of photopenia on the renal scan. We assessed the following 3 models: clinical (demographic information, fever, and etiologic organism) and ultrasonographic findings (model 1); model 1 plus serum levels of inflammatory markers (model 2); and model 2 plus voiding cystourethrogram findings (model 3). RESULTS Of the 1280 included participants, 199 (15.5%) had renal scarring. A temperature of at least 39°C, an etiologic organism other than Escherichia coli, an abnormal ultrasonographic finding, polymorphonuclear cell count of greater than 60%, C-reactive protein level of greater than 40 mg/L, and presence of vesicoureteral reflux were all associated with the development of renal scars (P ≤ .01 for all). Although the presence of grade IV or V vesicoureteral reflux was the strongest predictor of renal scarring, this degree of reflux was present in only 4.1% of patients. The overall predictive ability of model 1 with 3 variables (temperature, ultrasonographic findings, and etiologic organism) was only 3% to 5% less than the predictive ability of models requiring a blood draw and/or a voiding cystourethrogram. Patients with a model 1 score of 2 or more (21.7% of the sample) represent a particularly high-risk group in whom the risk for renal scarring was 30.7%. At this cutoff, model 1 identified 44.9% of patients with eventual renal scarring. CONCLUSIONS AND RELEVANCE Children and adolescents with an abnormal renal ultrasonographic finding or with a combination of high fever (≥39°C) and an etiologic organism other than E coli are at high risk for the development of renal scarring.

Early Antibiotic Treatment for Pediatric Febrile Urinary Tract Infection and Renal Scarring.

IMPORTANCE Existing data regarding the association between delayed initiation of antimicrobial therapy and the development of renal scarring are inconsistent. OBJECTIVE To determine whether delay in the initiation of antimicrobial therapy for febrile urinary tract infections (UTIs) is associated with the occurrence and severity of renal scarring. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study that combined data from 2 previously conducted longitudinal studies (the Randomized Intervention for Children With Vesicoureteral Reflux trial and the Careful Urinary Tract Infection Evaluation Study). Children younger than 6 years with a first or second UTI were followed up for 2 years. EXPOSURE Duration of the childs fever prior to initiation of antimicrobial therapy for the index UTI. MAIN OUTCOMES AND MEASURES New renal scarring defined as the presence of photopenia plus contour change on a late dimercaptosuccinic acid renal scan (obtained at study exit) that was not present on the baseline scan. RESULTS Of the 482 children included in the analysis, 434 were female (90%), 375 were white (78%), and 375 had vesicoureteral reflux (78%). The median age was 11 months. A total of 35 children (7.2%) developed new renal scarring. Delay in the initiation of antimicrobial therapy was associated with renal scarring; the median (25th, 75th percentiles) duration of fever prior to initiation of antibiotic therapy in those with and without renal scarring was 72 (30, 120) and 48 (24, 72) hours, respectively (P = .003). Older age (OR, 1.03; 95% CI, 1.01-1.05), Hispanic ethnicity (OR, 5.24; 95% CI, 2.15-12.77), recurrent urinary tract infections (OR, 0.97; 95% CI, 0.27-3.45), and bladder and bowel dysfunction (OR, 6.44; 95% CI, 2.89-14.38) were also associated with new renal scarring. Delay in the initiation of antimicrobial therapy remained significantly associated with renal scarring even after adjusting for these variables. CONCLUSIONS AND RELEVANCE Delay in treatment of febrile UTIs and permanent renal scarring are associated. In febrile children, clinicians should not delay testing for UTI.

Pneumococcal Resistance and Serotype 19A in Pittsburgh-Area Children With Acute Otitis Media Before and After Introduction of 7-Valent Pneumococcal Polysaccharide Vaccine

Methods: Before and after introduction of pneumococcal conjugate vaccine (PCV7), the authors obtained nasopharyngeal (NP) specimens from 3 groups of children aged 6 to 23 months with acute otitis media (AOM): group 1 (pre-PCV7), group 2 (early post-PCV7), and group 3 (late post-PCV7). Results: Of the Streptococcus pneumoniae isolates, the proportion that were vaccine serotypes (VTs) declined progressively (60.4% vs 48.6% vs 5.2% in groups 1, 2, and 3, respectively; P < .001). Concurrently, increases occurred in the proportion of penicillin-nonsusceptible isolates (minimum inhibitory concentration >0.1 µg/mL; 26.7% vs 37.8% vs. 38.5%; P = .12); the proportion of isolates that were serotype 19A (4.0% vs 0% vs 25.9%; P < .001); and the proportion of 19A isolates that were penicillin-nonsusceptible (0% in group 1, 68.6% in group 3; P = .004). Conclusion: Shifts in pneumococcal serotype distribution and increases in penicillin nonsusceptibility among pneumococcal isolates from children with AOM underscore the need for continuing bacteriological surveillance for future vaccine development.

Association Between Uropathogen and Pyuria

OBJECTIVE: We sought to determine factors associated with the absence of pyuria in symptomatic children whose urine culture was positive for a known uropathogen. METHODS: We obtained data on children evaluated at the Children’s Hospital of Pittsburgh emergency department between 2007 and 2013 with symptoms of urinary tract infection (UTI) who had paired urinalysis and urine cultures. We excluded children with an unknown or bag urine collection method, major genitourinary anomalies, immunocompromising conditions, or with multiple organisms on culture. We chose a single, randomly-selected urine specimen per child and limited the analysis to those with positive cultures. RESULTS: There were 46 158 visits during the study period; 1181 children diagnosed with UTI met all inclusion criteria and had a microscopic urinalysis for pyuria. Pyuria (≥5 white blood cells per high-powered field or ≥10 white blood cells per cubic millimeter) was present in 1031 (87%) children and absent in 150 (13%). Children with Enterococcus species, Klebsiella species, and Pseudomonas aeruginosa were significantly less likely to exhibit pyuria than children with Escherichia coli (odds ratio of 0.14, 0.34, and 0.19, respectively). Children with these organisms were also less likely to have a positive leukocyte esterase on dipstick urinalysis. Results were similar when we restricted the analysis to children whose urine samples were collected by bladder catheterization. CONCLUSIONS: We found that certain uropathogens are less likely to be associated with pyuria in symptomatic children. Identification of biomarkers more accurate than pyuria or leukocyte esterase may help reduce over- and undertreatment of UTIs.

Recurrent Urinary Tract Infections in Children With Bladder and Bowel Dysfunction.

BACKGROUND: Little generalizable information is available on the outcomes of children diagnosed with bladder and bowel dysfunction (BBD) after a urinary tract infection (UTI). Our objectives were to describe the clinical characteristics of children with BBD and to examine the effects of BBD on patient outcomes in children with and without vesicoureteral reflux (VUR). METHODS: We combined data from 2 longitudinal studies (Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) in which children <6 years of age with a first or second UTI were followed for 2 years. We compared outcomes for children with and without BBD, children with and without VUR, and children with VUR randomly assigned to prophylaxis or placebo. The outcomes examined were incidence of recurrent UTIs, renal scarring, surgical intervention, resolution of VUR, and treatment failure. RESULTS: BBD was present at baseline in 54% of the 181 toilet-trained children included; 94% of children with BBD reported daytime wetting, withholding maneuvers, or constipation. In children not on antimicrobial prophylaxis, 51% of those with both BBD and VUR experienced recurrent UTIs, compared with 20% of those with VUR alone, 35% with BBD alone, and 32% with neither BBD nor VUR. BBD was not associated with any of the other outcomes investigated. CONCLUSIONS: Among toilet-trained children, those with both BBD and VUR are at higher risk of developing recurrent UTIs than children with isolated VUR or children with isolated BBD and, accordingly, exhibit the greatest benefit from antimicrobial prophylaxis.

Development of an Algorithm for the Diagnosis of Otitis Media

BACKGROUND The relative importance of signs and symptoms in the diagnosis of otitis media has not been adequately evaluated. This has led to a large degree of variation in the criteria used to diagnose otitis media, which has resulted in inconsistencies in clinical care and discrepant research findings. METHODS A group of experienced otoscopists examined children presenting for primary care. We investigated the signs and symptoms that these otoscopists used to distinguish acute otitis media (AOM), otitis media with effusion (OME), and no effusion. We used recursive partitioning to develop a diagnostic algorithm. To assess the algorithm, we validated it in an independent dataset. RESULTS Bulging of the tympanic membrane (TM) was the main finding that otoscopists used to discriminate AOM from OME; information regarding the presence or absence of other signs and symptoms added little to the diagnostic process. Overall, 92% of children with AOM had a bulging TM compared with 0% of children with OME. Opacification and/or an air-fluid level was the main finding that the otoscopists used to discriminate OME from no effusion; 97% of children diagnosed with OME had an opaque TM compared with 5% of children diagnosed with no effusion. An algorithm that used bulging and opacification of the TM correctly classified 99% of ears in an independent dataset. CONCLUSIONS Bulging of the TM was the finding that best discriminated AOM from OME. The algorithm developed here may prove to be useful in clinical care, research, and education concerning otitis media.

Automated diagnosis of otitis media: vocabulary and grammar

We propose a novel automated algorithm for classifying diagnostic categories of otitis media: acute otitis media, otitis media with effusion, and no effusion. Acute otitis media represents a bacterial superinfection of the middle ear fluid, while otitis media with effusion represents a sterile effusion that tends to subside spontaneously. Diagnosing children with acute otitis media is difficult, often leading to overprescription of antibiotics as they are beneficial only for children with acute otitis media. This underscores the need for an accurate and automated diagnostic algorithm. To that end, we design a feature set understood by both otoscopists and engineers based on the actual visual cues used by otoscopists; we term this the otitis media vocabulary. We also design a process to combine the vocabulary terms based on the decision process used by otoscopists; we term this the otitis media grammar. The algorithm achieves 89.9% classification accuracy, outperforming both clinicians who did not receive special training and state-of-the-art classifiers.

How do parents of preverbal children with acute otitis media determine how much ear pain their child is having

UNLABELLED The objective of this study was to determine how parents of preverbal children determine whether their child is having otalgia. We constructed 8 cases describing a 1-year-old child with acute otitis media (AOM) using various combinations of the following 6 observable symptoms: fussiness, ear tugging, eating less, fever, sleeping difficulty, and playing less. Parents of children with a history of AOM presenting for well or sick appointments to an ambulatory clinic were asked to assign a pain level to each case on a visual analog scale. Sixty-nine parents participated in the study. Each of the 6 behaviors was associated with increased pain levels (P < .0001). Ear tugging and fussiness had the highest impact on the assigned pain levels. Higher level of parental education and private insurance were associated with higher reported pain levels (P = .007 and P = .001, respectively). Because interpretation of symptoms appears to be influenced by socioeconomic status, we question the utility of using an overall pain score from a 1-item parent scale as an outcome measure in clinical trials that include preverbal children. PERSPECTIVE Parents of preverbal children with acute otitis media use observable behaviors to determine their childs pain level. Interpretation of symptoms, however, appears to be influenced by socioeconomic status. Thus, we question the utility of using a 1-item parental pain scale in clinical trials that include preverbal children.

Identifying Children with Vesicoureteral Reflux: A Comparison of 2 Approaches

PURPOSE Various screening approaches have been proposed to identify the subgroup of children with urinary tract infection who have vesicoureteral reflux. However, few studies have compared the sensitivity of screening approaches in a representative population of young children. We compared the sensitivities of the top-down ((99m)technetium dimercaptosuccinic acid renal scan to screen) and biomarker based (C-reactive protein level at presentation) approaches in identifying children with vesicoureteral reflux. MATERIALS AND METHODS We calculated the sensitivity of the 2 screening approaches in detecting vesicoureteral reflux and subsequently high grade (III or greater) vesicoureteral reflux in children. RESULTS The top-down and C-reactive protein based approaches missed 33% and 29% of cases of high grade vesicoureteral reflux, respectively. CONCLUSIONS The sensitivity of the top-down approach for detecting high grade vesicoureteral reflux was lower than previously reported. Further study of novel methods to identify children at risk for renal scarring is warranted.

Light field otoscope design for 3D in vivo imaging of the middle ear

We present a light field digital otoscope designed to measure three-dimensional shape of the tympanic membrane. This paper describes the optical and anatomical considerations we used to develop the prototype, along with the simulation and experimental measurements of vignetting, field curvature, and lateral resolution. Using an experimental evaluation procedure, we have determined depth accuracy and depth precision of our system to be 0.05-0.07 mm and 0.21-0.44 mm, respectively. To demonstrate the application of our light field otoscope, we present the first three-dimensional reconstructions of tympanic membranes in normal and otitis media conditions, acquired from children who participated in a feasibility study at the Childrens Hospital of Pittsburgh of the University of Pittsburgh Medical Center.