Caregiver Values and Preferences Related to Surgical Decision-making for Children with Medical Complexity.

OBJECTIVE: To uncover the values and preferences of the caregivers for children with medical complexity (CMC), using the test case of surgical treatment decision-making for pediatric neuromuscular scoliosis (NMS) that will inform the future development of a decision support tool in this population. STUDY DESIGN: We conducted a qualitative study of semi-structured interviews of English- and Spanish-speaking caregivers of children with NMS from two geographically distinct children's hospitals. We used purposive sampling of language and treatment options selected to capture diverse experiences. Analysis was based on grounded theory with synthesized caregiver values and preferences themes. RESULTS: From 47 participants, we completed 41 interviews (9 in Spanish). Caregivers had a mean age of 43.2 years, were mostly White (66%), and had children with a mean age of 15.6. 64% chose surgery. The following values and preferences were important to many caregivers: reducing scoliosis-related pain, minimizing mobility limitations to optimize socio-emotional quality of life, limiting the impact of comorbidities on overall quality of life, information provided by peer support, the uncertainty of outcomes due to underlying comorbidities, and the uncertainty related to the anticipated progression of their child's scoliosis curve. Caregivers experienced immense uncertainty related to treatment outcomes due to their child's comorbidities. CONCLUSIONS: Caregivers of CMC may benefit from decision support that includes both values clarification exercises to help caregivers identify what of the many possible values and preferences are important to them and novel methods to communicate uncertainty in the care of CMC.

Antibiotic impregnated catheters and intrathecal antibiotics for CSF shunt infection prevention in children undergoing low-risk CSF shunt surgery.

BACKGROUND: Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007-2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012-2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children. METHODS: A retrospective observational cohort study at 6 tertiary care children's hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. RESULTS: A total of 1723 children underwent initial shunt placement between 2007-2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82-1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56-1.49, p = 0.7) compared to standard care. CONCLUSION: In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.

Lower levels of Th1 and Th2 cytokines in cerebrospinal fluid (CSF) at the time of initial CSF shunt placement in children are associated with subsequent shunt revision surgeries.

OBJECTIVE: We compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries. METHODS: This pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt revision surgeries during >=24 months of follow-up (n = 7); as well as children who underwent an initial CSF shunt placement and then required repeated CSF shunt revision surgeries (n = 3). Levels of 92 human cytokines were measured using the Olink immunoassay and 41 human cytokines were measured using Luminex based bead array on CSF obtained at the time of each child's initial CSF shunt placement and were displayed in heat maps. RESULTS: Qualitatively similar profiles for the majority of cytokines were observed among the patients in each group in both Olink and Luminex assays. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Pro- and anti-inflammatory cytokines were selected a priori and shown across subsequent revision surgeries for the 3 patients. Cytokine patterns differed between patients, but within a given patient pro-inflammatory and anti-inflammatory cytokines acted in a parallel fashion, with the exception of IL-4. CONCLUSIONS: Heat maps of cytokine levels at the time of initial CSF shunt placement for each child undergoing only a single initial CSF shunt placement and for each child undergoing repeat CSF shunt revision surgeries demonstrated qualitatively similar profiles for the majority of cytokines. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Better stratification by patient age, etiology, and mechanism of failure is needed to develop a deeper understanding of the mechanism of inflammation in the development of hydrocephalus and response to shunting in children.

Creating synthetic patient data to support the design and evaluation of novel health information technology.

To ensure that new health information technology supports its intended users, researchers and developers need to follow human-centered methods during all stages of the software development lifecycle, including early stage evaluations. These evaluations need to include realistic testing scenarios to ensure that they provide valuable and accurate feedback to system developers. However, obtaining realistic patient data to support these evaluations has many challenges, including the risk of re-identifying anonymized patients as well as the costs associated with connecting test systems with production ready clinical databases. Here we present a novel five-step process to create highly structured and realistic synthetic patient data to support the evaluation and comparison of early to middle stage health information technology prototypes. We applied this method to evaluate and compare three novel health information technology prototypes designed to support clinicians during the identification of high-priority patients when answering the question: "What patient should I see first?" Our novel approach fills an important gap in the evaluation of health information technology and assists designers in creating high-quality software that best supports its end users.

Development of Chronic Pseudomonas aeruginosa-Positive Respiratory Cultures in Children with Tracheostomy.

BACKGROUND: Up to 90% of children develop Pseudomonas aeruginosa (Pa)-positive respiratory cultures after tracheotomy. OBJECTIVE: To identify the factors associated with chronic Pa-positive respiratory cultures in the first 2 years after tracheotomy. METHODS: We conducted a retrospective cohort study of 210 children ≤ 18 years old who underwent tracheotomy at a single freestanding children's hospital that had two or more years of respiratory cultures post-tracheotomy available for analysis. We conducted multivariable logistic regression to test the association between demographic and clinical factors to our primary outcome of chronic Pa infection, defined as > 75% of respiratory cultures positive for Pa in the first 2 years after tracheotomy. RESULTS: Of the primarily male (61%), Hispanic (68%), and publicly insured (88%) cohort, 18% (n = 37) developed chronic Pa-positive respiratory cultures in the first 2 years. On multivariable logistic regression, pre-tracheotomy Pa-positive respiratory culture (aOR 11.3; 95% CI 4-1.5) and discharge on beta agonist (aOR 6.3; 95% CI 1.1-36.8) were independently associated with chronic Pa-positive respiratory cultures, while discharge on chronic mechanical ventilation was associated with decreased odds (aOR 0.3; 95% CI 0.1-0.7). On sensitivity analysis examining those without a pre-tracheotomy Pa-positive respiratory culture, discharge on MV continued to be associated with decreased odds of chronic Pa (aOR 0.1; 95% CI 0.02-0.4) and three other variables (male gender, chronic lung disease, and discharge on inhaled corticosteroids) were associated with increased odds of chronic Pa. CONCLUSION: Because pre-tracheotomy Pa growth on respiratory culture is associated with post-tracheotomy chronic Pa-positive respiratory cultures, future research should examine pre-tracheotomy Pa eradication or suppression protocols.

Caring for Children with Medical Complexity: Perspectives of Primary Care Providers.

OBJECTIVE: To describe typical care experiences and key barriers and facilitators to caring for children with medical complexity (CMC) from the perspective of community primary care providers (PCPs). STUDY DESIGN: PCPs participating in a randomized controlled trial of a care-coordination intervention for CMC were sent a 1-time cross-sectional survey that asked PCPs to (1) describe their experiences with caring for CMC; (2) identify key barriers affecting their ability to care for CMC; and (3) prioritize facilitators enhancing their ability to provide care coordination for CMC. PCP and practice demographics also were collected. RESULTS: One hundred thirteen of 155 PCPs sent the survey responded fully (completion rate = 73%). PCPs endorsed that medical characteristics such as polypharmacy (88%), multiorgan system involvement (84%), and rare/unfamiliar diagnoses (83%) negatively affected care. Caregivers with high needs (88%), limited time with patients and caregivers (81%), and having a large number of specialists involved in care (79%) were also frequently cited. Most commonly endorsed strategies to improve care coordination included more time with patients/caregivers (84%), summative action plans (83%), and facilitated communication (eg, e-mail, phone meetings) with specialists (83%). CONCLUSIONS: Community PCPs prioritized more time with patients and their families, better communication with specialists, and summative action plans to improve care coordination for this vulnerable population. Although this study evaluated perceptions rather than actual performance, it provides insights to improve understanding of which barriers and facilitators ideally might be targeted first for care delivery redesign.

Pediatric Critical Care Resource Use by Children with Medical Complexity.

OBJECTIVES: To examine the proportionate use of critical care resources among children of differing medical complexity admitted to pediatric intensive care units (ICUs) in tertiary-care children's hospitals. STUDY DESIGN: This is a retrospective, cross-sectional study of all children (<19 years of age) admitted to a pediatric ICU between January 1, 2012, and December 31, 2013, in the Pediatric Health Information Systems database. Using the Pediatric Medical Complexity Algorithm, we assigned patients to 1 of 3 categories: no chronic disease, noncomplex chronic disease (NC-CD), or complex chronic disease (C-CD). Baseline demographics, hospital costs, and critical care resource use were stratified by these groups and summarized. RESULTS: Of 136 133 children with pediatric ICU admissions, 53.0% were categorized as having C-CD. At the individual-encounter level, ICU resource use was greatest among patients with C-CD compared with children with NC-CD and no chronic disease. At the hospital level, patients with C-CD accounted for more than 75% of all examined ICU resources, including ventilation days, ICU costs, extracorporeal membrane oxygenation runs, and arterial and central venous catheters. Children with a progressive condition accounted for one-half of all ICU resources. In contrast, patients with no chronic disease and NC-CD accounted for less than one-quarter of all ICU therapies. CONCLUSION: Children with medical complexity disproportionately use the majority of ICU resources in children's hospitals. Efforts to improve quality and provide cost-effective care should focus on this population.

Variability in Management of First Cerebrospinal Fluid Shunt Infection: A Prospective Multi-Institutional Observational Cohort Study.

OBJECTIVES: To describe the variation in approaches to surgical and antibiotic treatment for first cerebrospinal fluid (CSF) shunt infection and adherence to Infectious Diseases Society of America (IDSA) guidelines. STUDY DESIGN: We conducted a prospective cohort study of children undergoing treatment for first CSF infection at 7 Hydrocephalus Clinical Research Network hospitals from April 2008 through December 2012. Univariate analyses were performed to describe the study population. RESULTS: A total of 151 children underwent treatment for first CSF shunt-related infection. Most children had undergone initial CSF shunt placement before the age of 6 months (n = 98, 65%). Median time to infection after shunt surgery was 28 days (IQR 15-52 days). Surgical management was most often shunt removal with interim external ventricular drain placement, followed by new shunt insertion (n = 122, 81%). Median time from first negative CSF culture to final surgical procedure was 14 days (IQR 10-21 days). Median duration of intravenous (IV) antibiotic use duration was 19 days (IQR 12-28 days). For 84 infections addressed by IDSA guidelines, 7 (8%) met guidelines and 61 (73%) had longer duration of IV antibiotic use than recommended. CONCLUSIONS: Surgical treatment for infection frequently adheres to IDSA guidelines of shunt removal with external ventricular drain placement followed by new shunt insertion. However, duration of IV antibiotic use in CSF shunt infection treatment was consistently longer than recommended by the 2004 IDSA guidelines.

Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study.

OBJECTIVE: To quantify the extent to which cerebrospinal fluid (CSF) shunt revisions are associated with increased risk of CSF shunt infection, after adjusting for patient factors that may contribute to infection risk. STUDY DESIGN: We used the Hydrocephalus Clinical Research Network registry to assemble a large prospective 6-center cohort of 1036 children undergoing initial CSF shunt placement between April 2008 and January 2012. The primary outcome of interest was first CSF shunt infection. Data for initial CSF shunt placement and all subsequent CSF shunt revisions prior to first CSF shunt infection, where applicable, were obtained. The risk of first infection was estimated using a multivariable Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HRs) with 95% CI. RESULTS: Of the 102 children who developed first infection within 12 months of placement, 33 (32%) followed one or more CSF shunt revisions. Baseline factors independently associated with risk of first infection included: gastrostomy tube (HR 2.0, 95% CI, 1.1, 3.3), age 6-12 months (HR 0.3, 95% CI, 0.1, 0.8), and prior neurosurgery (HR 0.4, 95% CI, 0.2, 0.9). After controlling for baseline factors, infection risk was most significantly associated with the need for revision (1 revision vs none, HR 3.9, 95% CI, 2.2, 6.5; ≥2 revisions, HR 13.0, 95% CI, 6.5, 24.9). CONCLUSIONS: This study quantifies the elevated risk of infection associated with shunt revisions observed in clinical practice. To reduce risk of infection risk, further work should optimize revision procedures.

Cerebrospinal Fluid Shunt Infections.

Cerebrospinal fluid (CSF) shunt infections are a particularly challenging clinical problem. This review article addresses epidemiology and microbiology of CSF shunt infections. Clinical care is reviewed in detail, including recent guidelines and systematic review articles. Finally, current research into prevention and treatment is highlighted, with a discussion on the mechanisms of infection.

National Characteristics of Emergency Care for Children with Neurologic Complex Chronic Conditions.

Introduction: Most pediatric emergency care occurs in general emergency departments (GED), where less pediatric experience and lower pediatric emergency readiness may compromise care. Medically vulnerable pediatric patients, such as those with chronic, severe, neurologic conditions, are likely to be disproportionately affected by suboptimal care in GEDs; however, little is known about characteristics of their care in either the general or pediatric emergency setting. In this study our objective was to compare the frequency, characteristics, and outcomes of ED visits made by children with chronic neurologic diseases between general and pediatric EDs (PED). Methods: We conducted a retrospective analysis of the 2011-2014 Nationwide Emergency Department Sample (NEDS) for ED visits made by patients 0-21 years with neurologic complex chronic conditions (neuro CCC). We compared patient, hospital, and ED visits characteristics between GEDs and PEDs using descriptive statistics. We assessed outcomes of admission, transfer, critical procedure performance, and mortality using multivariable logistic regression. Results: There were 387,813 neuro CCC ED visits (0.3% of 0-21-year-old ED visits) in our sample. Care occurred predominantly in GEDs, and visits were associated with a high severity of illness (30.1% highest severity classification score). Compared to GED visits, PED neuro CCC visits were comprised of individuals who were younger, more likely to have comorbid conditions (32.9% vs 21%, P < 0.001), and technology assistance (65.4% vs. 45.9%) but underwent fewer procedures and had lower ED charges ($2,200 vs $1,520, P < 0.001). Visits to PEDs had lower adjusted odds of critical procedures (adjusted odds ratio [aOR] 0.74, 95% confidence interval [CI] 0.62-0.87), transfers (aOR 0.14, 95% CI 0.04-0.56), and mortality (aOR 0.38, 95% CI 0.19-0.75) compared to GEDs. Conclusion: Care for children with neuro CCCs in a pediatric ED is associated with less resource utilization and lower rates of transfer and mortality. Identifying features of PED care for neuro CCCs could lead to lower costs and mortality for this population.

A search for bacteria identified from cerebrospinal fluid shunt infections in previous surgical events.

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on aerobic and anaerobic media. The detection and identification of bacteria was done with high throughput DNA sequencing methods and mass spectrometry. The presence of bacteria was confirmed in 4 infection samples, of which 2 were after initial placement and 2 after revision surgery. Taxonomic identification was consistent with clinical microbiology laboratory results. Bacteria were not detected in any of the CSF samples collected at the time of the previous surgical events. While our findings do not provide direct evidence for long-term persistence of pathogens, they suggest the need for consideration of additional source material, such as biofilm and environmental swabs, and/or the use of more sensitive and specific analytical methods.

Utilization trends in cerebrospinal fluid shunt infection prevention techniques in the United States from 2007 to 2015.

OBJECTIVE: The objective of this study was to describe trends in the utilization of infection prevention techniques (standard care, intrathecal [IT] antibiotics, antibiotic-impregnated catheters [AICs], and combination of IT antibiotics and AICs) among participating hospitals over time. METHODS: This retrospective cohort study at six large children's hospitals between 2007 and 2015 included children ≤ 18 years of age who underwent initial shunt placement between 2007 and 2012. Pediatric Health Information System + (PHIS+) data were augmented with chart review data for all shunt surgeries that occurred prior to the first shunt infection. The Pearson chi-square test was used to test for differences in outcomes. RESULTS: In total, 1723 eligible children had initial shunt placement between 2007 and 2012, with 3094 shunt surgeries through 2015. Differences were noted between hospitals in gestational age, etiology of hydrocephalus, and race and ethnicity, but not sex, weight at surgery, and previous surgeries. Utilization of infection prevention techniques varied across participating hospitals. Hydrocephalus Clinical Research Network hospitals used more IT antibiotics in 2007-2011; after 2012, increasing adoption of AICs was observed in most hospitals. CONCLUSIONS: A consistent trend of decreasing IT antibiotic use and increased AIC utilization was observed after 2012, except for hospital B, which consistently used AICs.

Factors associated with tracheostomy-associated infection treatment: A multicenter observational study.

OBJECTIVE: To characterize factors that influence the decision to treat suspected pediatric bacterial tracheostomy-associated respiratory infections (bTRAINs; e.g., pneumonia, tracheitis). METHODS: We conducted a multicenter, prospective cohort study of children with pre-existing tracheostomy hospitalized at six children's hospitals for a suspected bTRAIN (receipt of respiratory culture plus ≥1 doses of an antibiotic within 48 h). The primary predictor was respiratory culture growth categorized as Pseudomonas aeruginosa, P. aeruginosa + ≥1 other bacterium, other bacteria alone, or normal flora/no growth. Our primary outcome was bTRAIN treatment with a complete course of antibiotics as documented by the discharge team. We used logistic regression with generalized estimating equations to identify the association between our primary predictor and outcome and to identify demographic, clinical, and diagnostic testing factors associated with treatment. RESULTS: Of the 440 admissions among 289 patients meeting inclusion criteria, 307 (69.8%) had positive respiratory culture growth. Overall, 237 (53.9%) of admissions resulted in bTRAIN treatment. Relative to a negative culture, a culture positive for P. aeruginosa plus ≥1 other organism (adjusted odds ratio [aOR] 2.3; 95% confidence interval [CI] 1.02-5.0)] or ≥1 other organism alone (aOR: 2.8; 95% CI: 1.4-5.6)] was associated with treatment. Several clinical and diagnostic testing (respiratory Gram-stain and chest radiograph) findings were also associated with treatment. Positive respiratory viral testing was associated with reduced odds of treatment (aOR: 0.5; 95% CI: 0.2-0.9). CONCLUSIONS: Positive respiratory cultures as well as clinical indicators of acute illness and nonculture test results were associated with bTRAIN treatment. Clinicians may be more comfortable withholding antibiotics when a virus is identified during testing.

Infection rates during eras of intrathecal antibiotic use followed by antibiotic-impregnated catheter use in prevention of cerebrospinal fluid shunt infection.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) implemented a perioperative infection prevention bundle for all CSF shunt surgeries in 2007 that included the relatively unproven technique of intrathecal instillation of the broad-spectrum antibiotics vancomycin and gentamicin into the shunt. In the meantime, the field debated the use of antibiotic-impregnated catheter (AIC) shunt tubing using clindamycin and rifampin, an increasingly widespread, but expensive and controversial, technique. It is unknown whether there were changes in infecting organisms associated with the use of these techniques during CSF shunt surgery at the hospital level. Key comparison periods include during the use of intrathecal antibiotics (period 1 from June 1, 2007, to December 31, 2011, at HCRN hospitals) and AIC (period 2 from January 1, 2012, to December 31, 2015, at HCRN as well as increasing over time at non-HCRN hospitals) and only standard use of routine prophylactic antibiotics (period 1 at non-HCRN hospitals). The aim of this study was to examine rates of CSF shunt surgery-related infections from 2007 to 2012 at the hospital level, including HCRN and non-HCRN hospitals, with a focus on infections with gram-negative organisms. METHODS: The authors conducted a retrospective observational cohort study at 6 children's hospitals with enrollment from 2007 to 2012 and surveillance through 2015. Bimonthly rates of shunt surgery-related infections were summarized to produce an overall hospital-specific time series, as well as by HCRN/non-HCRN status. An interrupted time series analysis was performed to assess the impact of change in HCRN perioperative infection prevention bundle on overall bimonthly infection rates. Quarterly rates of gram-negative shunt surgery-related infections were summarized to produce an overall hospital-specific time series. RESULTS: The overall bimonthly CSF shunt infection rate over time did not change significantly from 2007 to 2012. There was no difference in the trajectory of infection rates between HCRN and non-HCRN hospitals during the entire study period. No change in distributions of gram-negative organism infections was observed in hospitals from 2007 to 2015. CONCLUSIONS: There were no differences observed in hospital-level infection rates for low-risk patients undergoing CSF shunt surgery. This included analyses based on participation in the HCRN network, given their regular use of intrathecal antibiotics in period 1 and a focus on gram-negative infections with increasing adoption of AICs in period 2.

Neurodevelopmental and Mental Health Conditions in Children With Medical Complexity.

BACKGROUND AND OBJECTIVES: Children with medical complexity (CMC) may be at a high risk of neurodevelopmental and mental health conditions given disease comorbidities and lived experiences. Little is known about the prevalence of these conditions at a population level. In this study, we estimated the prevalence of neurodevelopmental and mental health diagnoses in CMC relative to children without medical complexity and measured associations between these diagnoses in CMC and subsequent health care utilization and in-hospital mortality. METHODS: We applied the Child and Adolescent Mental Health Disorders Classification System to identify neurodevelopmental and mental health diagnoses using all-payer claims data from three states (2012-2017). Poisson regression was used to compare outcomes in CMC with neurodevelopmental and mental health diagnoses to CMC without these diagnoses, adjusting for sociodemographic and clinical characteristics. RESULTS: Among 85 581 CMC, 39 065 (45.6%) had ≥1 neurodevelopmental diagnoses, and 31 703 (37.0%) had ≥1 mental health diagnoses, reflecting adjusted relative risks of 3.46 (3.42-3.50) for neurodevelopmental diagnoses and 2.22 (2.19-2.24) for mental health diagnoses compared with children without medical complexity. CMC with both neurodevelopmental and mental health diagnoses had 3.00 (95% confidence interval [CI]: 2.98-3.01) times the number of ambulatory visits, 69% more emergency department visits (rate ratio = 1.69, 95% CI: 1.66-1.72), 58% greater risk of hospitalization (rate ratio = 1.58, 95% CI: 1.50-1.67), and 2.32 times (95% CI: 2.28-2.36) the number of hospital days than CMC without these diagnoses. CONCLUSIONS: Neurodevelopmental and mental health diagnoses are prevalent among CMC and associated with increased health care utilization across the continuum of care. These findings illustrate the importance of recognizing and treating neurodevelopmental and mental health conditions in this population.

Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort. METHODS: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months. RESULTS: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013). CONCLUSIONS: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.

A Refined, Controlled 16S rRNA Gene Sequencing Approach Reveals Limited Detection of Cerebrospinal Fluid Microbiota in Children with Bacterial Meningitis.

Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. Additionally, these refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads, such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples with low bacterial loads by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial meningitis and compare results with those from microbiological cultures. Several bench and computational approaches were taken to address potential sources of error for low bacterial load samples. We compared DNA yields and sequencing results after applying three different DNA extraction approaches to an artificially constructed mock-bacterial community. We also compared two postsequencing computational contaminant removal strategies, decontam R and full contaminant sequence removal. All three extraction techniques followed by decontam R yielded similar results for the mock community. We then applied these methods to 22 CSF samples from children diagnosed with meningitis, which has low bacterial loads relative to other clinical infection samples. The refined 16S HTS pipelines identified the cultured bacterial genus as the dominant organism for only 3 of these samples. We found that all three DNA extraction techniques followed by decontam R generated similar DNA yields for mock communities at the low bacterial loads representative of CSF samples. However, the limits of detection imposed by reagent contaminants and methodologic bias precluded the accurate detection of bacteria in CSF from children with culture-confirmed meningitis using these approaches, despite rigorous controls and sophisticated computational approaches. Although we did not find current DNA-based diagnostics to be useful for pediatric meningitis samples, the utility of these methods for CSF shunt infection remains undefined. Future advances in sample processing methods to minimize or eliminate contamination will be required to improve the sensitivity and specificity of these methods for pediatric meningitis. IMPORTANCE Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. These refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial meningitis and compare results with those from microbiological cultures. We found that the limits of detection imposed by reagent contaminants and methodologic bias precluded the accurate detection of bacteria in CSF from children with culture-confirmed meningitis using these approaches, despite rigorous controls and sophisticated computational approaches.