Upper pole pathologies in duplex kidneys: an analysis of predictive factors for surgery and urinary tract infections from the Mid-Atlantic Pediatric Academic Consortium.

BACKGROUND/OBJECTIVE: While there is significant data on the natural history and outcomes for prenatal hydronephrosis in simplex kidneys, duplex kidneys tend to be less studied. Management can be quite variable based on provider preference. We aimed to describe practice patterns from several tertiary academic institutions, identify clinical predictors for surgical intervention and urinary tract infection (UTI) for upper pole pathology, and demonstrate the natural history of lower pole vesicoureteral reflux (VUR). METHODS: We conducted a retrospective review of patients from 4 Mid-Atlantic institutions between 2015 and 2020. Inclusion criteria included patients with a duplex kidney with upper pole pathology and/or lower pole VUR. The primary outcome was predictive factors for surgical intervention and UTI. The secondary outcome was to assess the natural history of lower pole VUR including resolution rates by grade. Linear regression identified clinical predictors for UTI events. Multivariate logistic regression identified predictors of surgical intervention, UTI, and lower pole VUR resolution. Descriptive statistics and regression modeling analyses were performed using SAS. RESULTS: Two hundred forty-two patients were included with a total of 271 duplex renal units. Hydronephrosis grade (both SFU and UTD grading) and number of prior UTI events were statistically significant predictors for surgical intervention (p = 0.03/0.001 and p = 0.002 respectively). Ectopic ureter (p = 0.004), ureterocele (p = 0.02), and obstruction (p = 0.04) were the only pathologies predictive for surgery. Male gender and circumcision were significantly associated with decreased UTI risk (p = 0.03 and p = 0.01). On linear regression modeling, antibiotic prophylaxis after the first year of life was associated with decreased risk of further UTI events (p = 0.03); however, antibiotic prophylaxis within the first year of life did not decrease UTI risk (p = 0.14). For VUR outcomes, 65.0% of grades 1-3 VUR and 52.2% of grades 4-5 had resolution/improvement at mean time of 2.1 years. There were no predictive factors for resolution/improvement of VUR. CONCLUSIONS: Hydronephrosis grade and UTI events were significant predictors for surgical intervention for upper pole pathology. Pathologies that were predictive for surgery included ectopic ureter, ureterocele and obstruction. Male gender, circumcision and antibiotic prophylaxis after the first year of life were associated with a decreased UTI risk. Roughly 58% of lower pole VUR spontaneously improved/resolved. Identification of these risk factors aids in standardization of care practices to reduce long-term UTI risk and inform counseling with families about possible need for surgical intervention and expectations for long term outcomes.

Predicting the likelihood of prolongation of half-time among infants with initially indeterminate drainage values: A single-institution retrospective study of 535 patients with ureteropelvic junction obstruction.

INTRODUCTION AND OBJECTIVE: Prior studies have shown a broad half time (T1/2) interval on MAG3 diuresis renography (DR) that is indeterminate for obstruction. We aimed to refine and sub-divide the indeterminate range and associate it with clinically meaningful outcomes: pyeloplasty and pyeloplasty-free survival. METHODS: We identified patients <1.5 years-old at presentation with unilateral, isolated moderate to severe hydronephrosis who underwent DR from 2000 to 2016. A logistic regression model was created using T1/2 to predict surgery. An indeterminate range was defined based on patients with <90% probability of pyeloplasty or resolution. This group was sub-divided into three T1/2 intervals: 5-20, 21-40, and 41-60 min. Endpoints were pyeloplasty and pyeloplasty free survival. Indications for surgery were loss of differential renal function (DRF), worsening T1/2, family preference, and/or pain. RESULTS: Among 2025 patients with DR, 704 met criteria (169 were lost to follow up). Of the remaining 535, 218 had pyeloplasties and 317 did not. The Pyeloplasty group had significantly worse DRF, T1/2 at initial DR, and exited the study earlier, at a median age 1.1years vs 2.3 years (p < 0.001). For all patients with antenatally detected unilateral UPJ obstruction, the odds of undergoing pyeloplasty at any time increased by 1.8 times (p < 0.001 [95% CI: 1.04, 1.08]) per 10 unit increase in T1/2 until T1/2 = 60. However, in patients with intermediate drainage, five year surgery-free survival probability for patients with T1/2 5-20, 21-40, and 41-60 min were 79.7%, 46.7% and 33.3% respectively (χ2 = 41.2, P = <0.001). DISCUSSION: Previous efforts to define indeterminate drainage resulted in ranges for T1/2 that were too broad to be clinically useful. Within our endpoint-defined indeterminate range, our data show that there are significant step offs in 5-year surgery-free survival for patients with T1/2 < 20 min, 21-40 min, and 41-60 min. Although there is a steady decrease in surgery-free survival among patients with a T1/2 of 21-40 min over the first 5 years of life, half can be managed nonoperatively. These patients likely represent the true intermediate risk group and closer follow up is justified. CONCLUSIONS: Initial T1/2 on DR is predictive of future surgery. When drainage is "indeterminate" for obstruction, sub-stratification allows for more accurate prognostication.

The association between urine neutrophil gelatinase-associated lipocalin and UTI in people with neurogenic lower urinary tract dysfunction.

STUDY DESIGN: Secondary analysis of urine samples collected from a prospective within-subject clinical trial. OBJECTIVES: Describe the baseline variation in urine neutrophil gelatinase-associated lipocalin (uNGAL) levels in adults with neurogenic lower urinary tract dysfunction (NLUTD) and determine if uNGAL levels vary according to likelihood of having a UTI. SETTING: Greater Washington D.C. region. METHODS: Urine samples were collected from a cohort of adults with NLUTD from a clinical trial. Samples were divided into groups of "Not UTI", "Unlikely UTI", and "Likely UTI" based on symptoms and urine culture results. uNGAL was compared between groups using Kruskal-Wallis and post hoc Dunn's test. Mixed effects logistic model was used to assess the association of uNGAL and Likely UTI. RESULTS: Twenty-seven participants provided a total of 104 samples. uNGAL levels were lowest for the No UTI group (n = 29; 37 ng/ml interquartile range (IQR) (15, 71)), intermediate for the Unlikely UTI group (n = 67; 95 ng/ml IQR (37, 161)) and highest for the Likely UTI group (n = 8; 187 ng/ml IQR(146, 224)). uNGAL levels were higher in those with Likely UTI compared to both Unlikely UTI (p < 0.05) and No UTI (p < 0.01). uNGAL had an association with Likely UTI (OR 1.01, 95% CI (1.00-1.02), p = 0.049). CONCLUSIONS: Adults with NLUTD have notable variation in uNGAL levels in the absence of symptoms potentially due to UTI. uNGAL levels are higher in those who are likely to have UTI have higher uNGAL levels compared to those with non-specific symptoms and/or less growth on urine culture. uNGAL may have utility as a marker of UTI in people with NLUTD. SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) funded this work. Bioporto provided partial salary support for SLG, IL, and OKL. NGAL ELISAs were provided by Bioporto in kind.

The Urine Microbiome of Healthy Men and Women Differs by Urine Collection Method.

PURPOSE: Compared to the microbiome of other body sites, the urinary microbiome remains poorly understood. Although noninvasive voided urine specimens are convenient, contamination by urethral microbiota may confound understanding of the bladder microbiome. Herein we compared the voiding- versus catheterization-associated urine microbiome of healthy men and women. METHODS: An asymptomatic, healthy cohort of 6 women and 14 men underwent midstream urine collection, followed by sterile catheterization of the bladder after bladder refilling. Urine samples underwent urine dipstick testing and conventional microscopy and urine cultures. Samples also underwent Illumina MiSeq-based 16S ribosomal RNA gene amplification and sequencing. RESULTS: All organisms identified by urine culture were also identified by 16S amplification; however, next-generation sequencing (NGS) also detected bacteria not identified by cultivation. Lactobacillus and Streptococcus were the most abundant species. Abundances of the 9 predominant bacterial genera differed between the urethra and bladder. Voided and catheterized microbiomes share all dominant (>1%) genera and Operational Taxonomic Units but in similar or different proportions. Hence, urethra and bladder microbiomes do not differ in taxonomic composition, but rather in taxonomic structure. Women had higher abundance of Lactobacillus and Prevotella than men. CONCLUSION: Our findings lend credence to the hypothesis that Lactobacilli are important members of the healthy urine microbiome. Our data also suggest that the microbiomes of the urethra and bladder differ from one another. In conclusion, urine collection method results in different 16S-based NGS data, likely due to the sensitivity of NGS methods enabling detection of urethral bacteria present in voided but not catheterized urine specimens.

Discrepant Rates of Hypospadias Surgical Complications: A Comparison of U.S. News & World Report and Pediatric Health Information System® Data and Published Literature.

PURPOSE: Complication rates of 5% to 10% and 12% to 23% have been observed following distal and proximal hypospadias repair, respectively. However, these rates may be overreported. We hypothesized that data from the Pediatric Health Information System would corroborate the complication rates reported in the literature and refute the rates established by U.S. News & World Report as quality metrics. MATERIALS AND METHODS: The Pediatric Health Information System database was interrogated for hypospadias and revision CPT® codes. To evaluate the appropriateness of the U.S. News & World Report code list to identify revisions, 3 CPT groups were defined. Group A included codes sought by U.S. News & World Report, group B included group A plus codes for acquired urethrocutaneous fistula in males and group C included group B plus any revision codes associated with the index procedures. To evaluate the appropriateness of U.S. News & World Report followup interval, we assessed revision rates with ever increasing followup intervals out to 7 years. Yearly revision rates were summarized by median and quantile to correlate whether median revision rates changed significantly depending on whether increased followup or enhanced code lists were used. RESULTS: Average complication rates for group A were 3.32% (range 0.48% to 7.36%) and 12.29% (3.48% to 36.36%) for distal and proximal repairs, respectively. Revision rates increased significantly from group A (median 3.32%) by inclusion of a more expansive list of CPT codes associated with revision procedures (group B, 4.26%, p <0.001 and group C, 6.37%, p <0.001) in distal hypospadias. Among proximal hypospadias cases this difference was not significant when comparing group A (12.29%) to group B (12.53%, p=0.813), but was significant when comparing group A to group C (22.14%, p <0.001). Median revision rates for distal and proximal hypospadias increased with longer followup for all 3 groups, although the upward trend was not statistically significant. CONCLUSIONS: Depending on how one defines hypospadias revision, no hospital within the Pediatric Health Information System data set meets the U.S. News & World Report definition of perfection, a finding that is supported by recent reports from some of the largest, most prolific and most highly regarded pediatric urology programs. We posit that the U.S. News & World Report quality metrics do not accurately reflect the nature of hypospadias surgery complication rates.

Intravesical Lactobacillus rhamnosus GG is safe and well tolerated in adults and children with neurogenic lower urinary tract dysfunction: first-in-human trial.

BACKGROUND: Urinary symptoms are common for people with neurogenic lower urinary tract dysfunction (NLUTD). No nonprescription approach has been proven safe and effective for self-management of urinary symptoms. Our objective was to describe the safety and tolerability of Lactobacillus rhamnosus GG (LGG®) instilled intravesically for self-management of inflammatory urinary symptoms in adults and children with NLUTD due to spinal cord injury or disease (SCI/D) and who use intermittent catheterization (IC). METHODS: A total of 103 individuals with SCI/D enrolled in an 18-month study consisting of three 6-month stages: baseline (weekly observation of urinary symptoms); intervention (self-instilled intravesical LGG® in response to more cloudy or foul-smelling urine); and washout (weekly observation of urinary symptoms). Urinary symptoms were assessed using the Urinary Symptom Questionnaire for people with neurogenic bladder using intermittent catheters (USQNB-IC). Safety was based on serious adverse events and adverse events (S/AEs) and trends in symptoms. Tolerability was defined as the independence of AE experience and willingness to use/pay for this intervention. RESULTS: A total of 74 (77%) adults and 6 (86%) of children completed the study, of whom 64 instilled LGG® for a total of 357 instillations (range 1-41 per person). There were 59 S/AEs, 44% (26/59) of which were categorized as infectious genitourinary. There was no statistical relationship between S/AEs and use or dose of the intervention. CONCLUSIONS: One or two doses of self-instilled intravesical LGG® in response to more cloudy or foul-smelling urine was safe and well tolerated among this sample of adults and children with SCI/D who have NLUTD and use IC.

Early Detection of Ureteropelvic Junction Obstruction Using Signal Analysis and Machine Learning: A Dynamic Solution to a Dynamic Problem.

PURPOSE: We sought to define features that describe the dynamic information in diuresis renograms for the early detection of clinically significant hydronephrosis caused by ureteropelvic junction obstruction. MATERIALS AND METHODS: We studied the diuresis renogram of 55 patients with a mean ± SD age of 75 ± 66 days who had congenital hydronephrosis at initial presentation. Five patients had bilaterally affected kidneys for a total of 60 diuresis renograms. Surgery was performed on 35 kidneys. We extracted 45 features based on curve shape and wavelet analysis from the drainage curves recorded after furosemide administration. The optimal features were selected as the combination that maximized the ROC AUC obtained from a linear support vector machine classifier trained to classify patients as with or without obstruction. Using these optimal features we performed leave 1 out cross validation to estimate the accuracy, sensitivity and specificity of our framework. Results were compared to those obtained using post-diuresis drainage half-time and the percent of clearance after 30 minutes. RESULTS: Our framework had 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases. This was a significant improvement over the same accuracy of 82%, including 71% sensitivity and 96% specificity obtained from half-time and 30-minute clearance using the optimal thresholds of 24.57 minutes and 55.77%, respectively. CONCLUSIONS: Our machine learning framework significantly improved the diagnostic accuracy of clinically significant hydronephrosis compared to half-time and 30-minute clearance. This aids in the clinical decision making process by offering a tool for earlier detection of severe cases and it has the potential to reduce the number of diuresis renograms required for diagnosis.

Prediction of Clinical Outcomes in Prenatal Hydronephrosis: Importance of Gravity Assisted Drainage.

PURPOSE: In infants with SFU (Society for Fetal Urology) grade 3-4 congenital hydronephrosis, 99mTc-mercaptoacetyltriglycine diuretic renography assesses differential function and drainage half-time. We routinely also include the percent of radiotracer drained after 30 minutes of diuresis as well as after 15 minutes with the patient in the upright position. We investigated whether any 1 or more of these parameters on initial diuretic renography predicts persistent or worsening drainage parameters. MATERIALS AND METHODS: Infants 6 months or younger with grade 3-4 congenital hydronephrosis who presented between January 2009 and December 2014 were identified from billing data and included in analysis if they underwent at least 1 baseline diuretic renography. Those with structural anomalies were excluded from study. Baseline and followup differential function, diuresis half-time, clearance at 30 minutes and clearance with the patient upright were abstracted and comparisons were made between those with initially indeterminate diuresis half-time who underwent pyeloplasty vs those showing spontaneous improvement. RESULTS: A total of 74 patients (82 renal units) with presumed ureteropelvic junction obstruction met inclusion/exclusion criteria. All 10 renal units with initial diuresis half-time less than 5 minutes resolved spontaneously and all 25 renal units with initial diuresis half-time greater than 75 minutes underwent pyeloplasty. Therefore, we defined the indeterminate group as the 47 renal units with initial half-time between 5 and 75 minutes. Of those 47 renal units with indeterminate initial diuresis half-time 23 (47%) underwent pyeloplasty and 25 (53%) resolved spontaneously. Indications for pyeloplasty included worsening in 17 cases, persistent obstruction in 4 and urinary tract infection in 1. Among renal units with indeterminate drainage clearance while upright and clearance at 30 minutes were the only variables that differed significantly between surgical cases and those that resolved spontaneously. CONCLUSIONS: Radiotracer clearance with the patient upright and clearance at 30 minutes are more predictive of surgical management than diuresis half-time or differential function for renal units with indeterminate drainage. They should be included in the standard assessment of ureteropelvic junction obstruction.

Redefining Healthy Urine: A Cross-Sectional Exploratory Metagenomic Study of People With and Without Bladder Dysfunction.

PURPOSE: We used the PathoScope platform to perform species level analyses of publicly available, 16S rRNA pyrosequenced, asymptomatic urine data to determine relationships between microbiomes, and clinical and functional phenotypes. MATERIALS AND METHODS: We reanalyzed previously reported, cross-sectionally acquired urine samples from 47 asymptomatic subjects, including 23 controls and 24 subjects with neuropathic bladder. Urine was originally collected by the usual method of bladder drainage and analyzed by urinalysis, culture and pyrosequencing. Urinalysis and culture values were stratified as leukocyte esterase (0, or 1 or greater), nitrite (positive or negative), pyuria (fewer than 5, or 5 or greater white blood cells per high power field), cloudy urine (positive or negative) and urine culture bacterial growth (less than 50,000, or 50,000 or greater cfu/ml). PathoScope was used for next generation sequencing alignment, bacterial classification and microbial diversity characterization. RESULTS: Subjects with neuropathic bladder were significantly more likely to have positive leukocyte esterase and pyuria, cloudy urine and bacterial growth. Of 47 samples 23 showed bacterial growth on culture and in all samples bacteria were identified by pyrosequencing. Nonneuropathic bladder urine microbiomes included greater proportions of Lactobacillus crispatus in females and Staphylococcus haemolyticus in males. The Lactobacillus community differed significantly among females depending on bladder function. Irrespective of gender the subjects with neuropathic bladder had greater proportions of Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumonia. In 4 subjects with neuropathic bladder Actinobaculum sp. was detected by sequencing and by PathoScope but not by cultivation and in all cases it was associated with pyuria. CONCLUSIONS: Using PathoScope plus 16S pyrosequencing we were able to identify unique, phenotype dependent, species level microbes. Novel findings included absent L. crispatus in the urine of females with neuropathic bladder and the presence of Actinobaculum only in subjects with neuropathic bladder.

Most infants with dilating vesicoureteral reflux can be treated nonoperatively.

PURPOSE: Dilating vesicoureteral reflux provokes concern for physicians and parents that often leads to corrective surgery in young children. Since there are limited data describing the natural history of dilating vesicoureteral reflux in infants, we identified factors predictive of resolution/improvement in infants initially treated nonoperatively. MATERIALS AND METHODS: We reviewed the medical records of 90 infants 6 months old or younger from 2004 to 2010 who were referred for prenatal hydronephrosis or initial febrile urinary tract infection and found to have dilating vesicoureteral reflux (grade 3 or greater). Variables of interest included presentation, dimercapto-succinic acid results, sex, breakthrough febrile urinary tract infections, reflux grade and bilateral reflux. Cox regression analysis was performed to determine predictors of spontaneous resolution and/or improvement to reflux grade less than 3 as well as predictors of surgical intervention. RESULTS: Included in final analysis were 80 infants (113 renal units). Of the patients 51 (64%) experienced spontaneous resolution/improvement with a mean followup of 29 months before resolution, discharge home and/or end of followup. Only 20 patients (25%) underwent surgery. Cox regression analysis revealed that a normal initial dimercapto-succinic acid scan, initial reflux grade less than 5 and absent breakthrough febrile urinary tract infections were predictive of reflux resolution/improvement (p <0.05). Dimercapto-succinic acid scan abnormalities, prenatal hydronephrosis and breakthrough febrile urinary tract infections were significant predictors of surgery (p <0.05). CONCLUSIONS: Dilating vesicoureteral reflux in infancy often resolves/improves spontaneously. Therefore, surgery should be directed toward patients unlikely to experience resolution, ie those with an abnormal initial dimercapto-succinic acid scan, grade 5 vesicoureteral reflux and breakthrough febrile urinary tract infections.

Evaluation of differential renal function and renographic patterns in patients with dietl crisis.

PURPOSE: We analyzed preoperative and postoperative differential renal function and characterized the renographic findings in patients with ureteropelvic junction obstruction associated with Dietl crisis. MATERIALS AND METHODS: Patients with Dietl crisis who underwent pyeloplasty between January 2004 and December 2010 were classified by renographic presentation. Patients in group 1 were diagnosed with cortical retention, those in group 2 had an initial obstructed scan (T1/2 of 20 minutes or more and no cortical retention) and those in group 3 had an initial nondiagnostic scan (T1/2 of less than 20 minutes and no cortical retention). Renographic parameters were used to analyze each group. RESULTS: A total of 59 patients met criteria for study inclusion. The 13 patients in group 1 demonstrated the most significant recovery of function after pyeloplasty (mean differential renal function change 13.59%). The 38 patients in group 2 exhibited a mean differential renal function change of 43.06% (range 20% to 54.6%) and mean preoperative T1/2 of 64.31 minutes. Pyeloplasty was performed in all 8 patients in group 3 based on subsequent diagnostic scan (4 patients) or increased hydronephrosis on other imaging associated with further symptomatic episodes (4). Initial renographic patterns noted in group 3 included biphasic curves, diminished clearance after 15 minutes upright or symptoms despite nonobstructive drainage. CONCLUSIONS: Interpretation of diuretic renography requires the assimilation of multiple parameters since patients with Dietl crisis can exhibit variability in renographic patterns due to the intermittent nature of ureteropelvic junction obstruction. Cortical retention represents a specific and pathognomic finding of acute ureteropelvic junction obstruction. With appropriate evaluation of these parameters, obstruction can be reliably diagnosed and appropriate surgical candidates chosen.

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury.

BACKGROUND: Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics. METHODS: A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample. RESULTS: A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated. CONCLUSIONS: Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of Lactobacillales in women and Corynebacterium in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.

Stable prevalence but changing risk factors for sudden infant death syndrome in child care settings in 2001.

OBJECTIVE: A total of 20% of sudden infant death syndrome (SIDS) cases in the 1990s occurred in child care settings. This is much higher than the 8% expected from Census Bureau data. Factors that were associated with child care SIDS included older age; white race; older, more educated mothers; and unaccustomed prone position. Since these findings, much emphasis has been placed on promoting a safe sleep environment in child care. The objectives of this study were to determine the proportion of SIDS occurring in child care in 2001 and to assess risk factors for SIDS in child care. METHODS: We conducted a retrospective review of all SIDS deaths that occurred in 2001 in 13 US states. Information regarding demographics, SIDS risk factors, and child care arrangements were collected and analyzed. Deaths that occurred in child care were compared with deaths that occurred during parental care. RESULTS: Of 480 deaths, 79 (16.5%) occurred in child care settings. Of these child care deaths, 36.7% occurred in family child care homes, 17.7% occurred in child care centers, 21.3% occurred in relative care, and 17.7% occurred with a nanny/babysitter at home. Infants in child care were more likely to be older and to die between the hours of 8 am and 4 pm and less likely to be exposed to secondhand smoke. There was no difference in usual, found, or placed sleep position between child care and home deaths. Approximately one half of the infants who died of SIDS in both settings were found prone, and 20% of deaths in both settings were among infants who were unaccustomed to prone sleep. CONCLUSIONS: The proportion of SIDS deaths in child care has declined slightly but still remains high at 16.5%. Infants in child care are no more likely to be placed or found prone and no more likely to be on an unsafe sleep surface. Educational efforts with child care providers have been effective and should be expanded to unregulated child care providers. In addition, there may be other, yet-unidentified factors in child care that place infants in those settings at higher risk for SIDS.

Characterizing vancomycin-resistant enterococci in neonatal intensive care.

Repetitive sequence-based polymerase chain reaction fingerprinting was used to characterize 23 vancomycin-nonsusceptible enterococcal isolates from 2003 to 2004. Five genetically related clusters spanned geographically distinct referring centers. DNA fingerprinting showed infant-to-infant transmission from referring institutions. Thus, community healthcare facilities are a source of vancomycin-nonsusceptible enterococci and should be targeted for increased infection control efforts.

Adverse events associated with dietary supplements: an observational study.

BACKGROUND: Adverse events associated with dietary supplements are difficult to monitor in the USA, because such products are not registered before sale, and there is little information about their content and safety. METHODS: In 1998, 11 poison control centres in the USA recorded details of 2332 telephone calls about 1466 ingestions of dietary supplements, in 784 of which patients had symptoms. We used a multitiered review process (kappa 0.42) to select 489 cases for whom we were at least 50% certain that their negative events were associated with dietary supplements. We aimed to assess the effects of multiple ingredients and long-term use, and collated data for patterns of use and information resources. FINDINGS: A third of events were of greater than mild severity. We noted both new and previously reported associations that included myocardial infarction, liver failure, bleeding, seizures, and death. Increased symptom severity was associated with use of several ingredients, long-term use, and age. Paediatric exposures were more often unintentional than were adult ingestions, and treatment of disease was the reason for supplement use in at least 28% of reports. Most products and ingredients were not identified in the information database (Poisindex) used by poison control centres, and specific adverse events were reported variably among five additional sources. INTERPRETATION: Dietary supplements are associated with adverse events that include all levels of severity, organ systems, and age groups. Associations between adverse events and ingredients are difficult to verify if a product has more than one ingredient, and because of incomplete information systems. Research into hazards and risks of dietary supplements should be a priority.

Risk of resistant infections with Enterobacteriaceae in hospitalized neonates.

OBJECTIVE: To determine the risk factors associated with progression from colonization to infection with health care-associated antimicrobial-nonsusceptible Enterobacteriaceae (ANE) in critically ill neonates. STUDY DESIGN: During a 3-year period (1998 to 2000), surveillance rectal cultures were performed on neonates admitted to our Level III neonatal intensive care unit after a cluster of four cases of ANE infection were identified in 1998. ANE were defined as members of the Enterobacteriaceae family that exhibited nonsusceptibility to ceftazidime or laboratory evidence of extended spectrum beta-lactamase (ESBL) production. RESULTS: A total of 1,710 patients were admitted to the neonatal intensive care unit during the study period. Of the 1,710 patients 300 (18%) were excluded from the risk factor analysis. Of the 1,410 remaining neonates the incidence of health care-associated ANE colonization was 17% (240 of 1,410 patients), and 14% of the colonized patients (34 of 240 patients) developed ANE infections. Of the 206 ANE-colonized patients who did not develop disease, 60 (29%) harbored ESBL-producing isolates. Of the 34 ANE-infected patients, 14 (41%) yielded growth of ESBL-producing isolates. Multiple logistic regression analysis revealed that colonized neonates with very low birth weights (<1,000 g) and those who had received prolonged exposures to antimicrobial agents were at increased risk of ANE infections. CONCLUSIONS: Colonization with ANE places hospitalized neonates at risk for development of systemic infections. Very low birth weight (<1,000 g) and prolonged exposure to antimicrobial agents were the only two independent risk factors associated with ANE infection.

The costs associated with nosocomial bloodstream infections in the pediatric intensive care unit.

OBJECTIVE: To assess the operational and subsidiary costs and length of stay (LOS) attributable to nosocomial bloodstream infections (BSI) in a pediatric intensive care unit (PICU). DESIGN: Matched case-control study. SETTING: Sixteen bed PICU in a 250-bed tertiary-care pediatric hospital. PATIENTS: Cases with BSI were prospectively identified from PICU patients who developed a nosocomial BSI from August 1996 to July 1998. Controls were PICU patients who were matched for age, severity of illness, diagnosis, and admission date who did not develop a nosocomial BSI. RESULTS: A total of 38 cases and 38 controls form the basis for this study. The cases and controls were similar with respect to the matching criteria. In addition, the cases and controls did not differ with respect to demographic characteristics or PICU survival. There was a trend toward increased hospital mortality among cases (23.7% vs. 10.5%, p =.084). Significant differences were encountered in the utilization of PICU therapeutic modalities. Cases were significantly less likely to be managed care plan enrollees (36.8% vs. 60.5%, p =.043). Total operational and subsidiary costs for radiology, pharmacy, and laboratory services were significantly higher for cases than controls ($78,272 vs. $35,005, $3,622 vs. $1,432, $8,635 vs. $4,630, and $8,648 vs. $3,971, respectively; all p <.001). The PICU and hospital LOS were significantly higher for cases than controls (19.3 vs. 4.6 days for PICU and 46.7 vs. 24.4 days for hospital; both p <.001). The operational costs attributable to nosocomial infection were $46,133. Radiology, pharmacy, and laboratory costs attributable to nosocomial infection were $2,364, $4,691, and $5,156, respectively. The PICU and hospital LOS attributable to a nosocomial BSI were 14.6 days and 21.1 days, respectively. The attributable mortality rate was 13.1%. CONCLUSIONS: The costs and LOS associated with nosocomial BSI in patients admitted to the PICU were significantly higher than controls.