Kathryn B. Whitlock

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.

Revision surgeries are associated with significant increased risk of subsequent cerebrospinal fluid shunt infection.

Background: The object of this study was to determine whether cerebrospinal fluid (CSF) shunt revision(s) are associated with increased risk of CSF shunt infection, after adjusting for baseline factors that contribute to infection risk. Methods: This was a retrospective cohort study of 579 children aged 0–18 years who underwent initial CSF shunt placement between January 01, 1997 and October 12, 2006 at a tertiary care children’s hospital. The outcome of interest was CSF shunt infection. Data for all subsequent CSF shunt revisions leading up to and including the initial CSF shunt infection, when applicable, were obtained. The likelihood of infection was determined using a Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HR) with 95% confidence intervals (CI). Results: There were 123 children who developed infection. Baseline factors independently associated with hazard of infection included age 0 to <6 months at CSF shunt placement (HR 2.4, 95% CI: 1.02–6.7) and myelomeningocele (HR 0.4, 95% CI: 0.2–0.8). Controlling for baseline factors, the risk of infection after shunt revision was significantly greater than at the time of initial placement (HR 3.0, 95% CI: 1.9–4.7), and this risk increased as numbers of revisions increased (≥2 revisions HR 6.5, 95% CI: 3.6–11.4). Conclusions: Although younger age is associated with increased hazard of infection, subsequent CSF shunt revision significantly increases infection risk.

Association of intraventricular hemorrhage secondary to prematurity with cerebrospinal fluid shunt surgery in the first year following initial shunt placement

OBJECT The neurosurgical literature has conflicting findings regarding the association between indications for CSF shunt placement and subsequent shunt surgery. The object of this study was to identify baseline factors at the time of initial CSF shunt placement that are independently associated with subsequent surgery. METHODS This was a retrospective cohort study of children ages 0-18 years who underwent initial CSF shunt placement between January 1, 1997, and October 12, 2006, at a tertiary care childrens hospital. The outcome of interest was CSF shunt surgery (either for revision or infection) within 12 months after initial placement. Associations between subsequent CSF shunt surgery and indication for the initial shunt, adjusting for patient age and surgeon factors at the time of initial placement, were estimated using multivariate logistic regression. Medical and surgical decisions, which varied according to surgeon, were examined separately in a univariate analysis. RESULTS Of the 554 children in the study cohort, 233 (42%) underwent subsequent CSF shunt surgery, either for revision (167 patients [30%]) or infection (66 patients [12%]). In multivariate logistic regression modeling, significant risk factors for subsequent CSF shunt surgery included (compared with aqueductal stenosis) intraventricular hemorrhage (IVH) secondary to prematurity (adjusted odds ratio [AOR] 2.2, 95% CI 1.1-4.5) and other unusual indications (AOR 3.7, 95% CI 1.0-13.6). The patients age at initial CSF shunt placement was not significantly associated with increased odds of subsequent surgery after adjusting for other associated factors. CONCLUSIONS The occurrence of IVH is associated with increased odds of subsequent CSF shunt surgery within 12 months after shunt placement. Families of and care providers for children with IVH should be attuned to their increased risk of shunt failure.

A Fitbit and Facebook mHealth intervention for promoting physical activity among adolescent and young adult childhood cancer survivors: A pilot study

Physical activity (PA) may be important for preventing chronic diseases for adolescent and young adult (AYA) childhood cancer survivors. Randomized controlled trials (RCTs) of PA interventions for AYA survivors are sparse, but necessary to determine effective programs for increasing PA among this population. Thus, we conducted a pilot RCT, testing the feasibility of a mobile health (mHealth) intervention to promote PA among AYA survivors.

Management of Toddler's Fractures in the Pediatric Emergency Department.

Objectives To evaluate current practice in treatment of toddler’s fractures, as well as subsequent healthcare utilization and complications. Methods Retrospective cohort study of children age 9 months to 3 years with a radiographically evident toddler’s fracture diagnosed at a single academic pediatric emergency department (PED) from January 2008 to December 2012. Data collected included initial form of immobilization (if any), referral to orthopedic clinic, number of repeat radiographs obtained, presence of skin breakdown related to splinting or casting, and presence of other complications. Results Seventy-five patients were treated. Most patients were placed in splints or casts in the PED (66.7%) as opposed to controlled ankle motion (CAM) boot (24%) or no immobilization (9.3%). Splinted patients had a longer total duration of immobilization, higher rate of follow-up in orthopedic clinic, and greater number of repeat radiographs obtained than those in the CAM boot or no immobilization groups. Thirteen patients (17.3%) developed skin breakdown during their course of therapy; all of these patients had been placed in a splint or cast in the PED. No difference in PED return rates was observed between groups. Conclusions There is wide variation in management of toddler’s fractures within this single tertiary care PED. Given that these fractures are unlikely to displace and that complications of splinting and casting are not insignificant, this study suggests that immobilization may not be necessary for acute management of toddler’s fractures.

Few Patient, Treatment, and Diagnostic or Microbiological Factors, Except Complications and Intermittent Negative Cerebrospinal Fluid (CSF) Cultures During First CSF Shunt Infection, Are Associated With Reinfection

BACKGROUND The relationship between first and subsequent cerebrospinal fluid (CSF) shunt infections is poorly understood. By understanding the factors associated with increased risk of reinfection, researchers may provide optimal treatment strategies at the time of first infection. The objective of this study was to describe and compare children with and without CSF shunt reinfection. METHODS A retrospective cohort study was performed among 118 children who underwent initial CSF shunt placement and developed first CSF shunt infection. The primary outcome variable was CSF shunt reinfection. Patient risk factors and medical and surgical management of initial CSF shunt placement and first CSF shunt infection were compared between children with and without reinfection. RESULTS Of 118 children with first infection, 31 (26%) developed a reinfection during the study period (overall median follow-up, 2096 days). Factors associated with reinfection in this cohort included ventriculoatrial or complex shunt at initial CSF shunt placement, complications after first CSF shunt infection, and intermittent negative CSF cultures. CONCLUSIONS Few patient or treatment factors were associated with reinfection. Factors associated with difficult-to-treat first CSF shunt infection, including complications after first CSF shunt infection and intermittent negative CSF cultures, were associated with reinfection. Clinicians who treat patients with unusual CSF shunts or more difficult first infections should have a high index of suspicion for reinfection after treatment is completed.

Piloting a mobile health intervention to increase physical activity for adolescents with ADHD

Physical activity (PA) reduces symptoms of Attention Deficit Hyperactivity Disorder (ADHD); interventions to increase PA may improve functioning and health for adolescents with ADHD. Mobile health (mHealth) technology and social media constitute promising interactive modalities for engaging adolescents—who are at highest risk for ADHD treatment drop-out—in interventions to increase PA. The current pilot study evaluated feasibility and acceptability of an innovative intervention incorporating an mHealth-linked wearable activity tracker (Fitbit Flex) and a Facebook group to increase PA among adolescents with ADHD. 11 adolescents diagnosed with ADHD (age 14–18, m = 15.5; 54% female) participated in a 4-week trial utilizing the Fitbit Flex in conjunction with (1) weekly personalized step count goals (2) social support through a Facebook group and (3) daily text messages about PA. The study took place in the greater Seattle, Washington area in the fall of 2015. Adolescents completed online surveys twice per week to rate their ADHD symptoms and positive and negative mood states, and parents rated adolescent ADHD symptoms weekly. Participants were adherent to the study protocol and acceptability of the intervention was high. Linear mixed models indicated that participants significantly increased their average weekly steps over the course of the study and demonstrated improvements in both adolescent and parent-reported ADHD Inattentive symptoms. Results indicate that this mHealth intervention is engaging and promising for increasing PA among adolescents with ADHD, and warrant further study. Implications for improving ADHD symptoms and overall functioning for this undertreated population are discussed.

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.

Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease

The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin (n = 9) or vehicle (n = 15) and people with long-standing type 1 diabetes, with (n = 37) or without (n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively (P < 0.001). Enzymatic activities of ACE, ACE2, and APA were 6.2-, 3.2-, and 18.8-fold higher, respectively, in diabetic animals (P < 0.001). Angiotensin II was 2.4-fold higher in diabetic animals (P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 109 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy.

Glenohumeral Dysplasia Following Neonatal Brachial Plexus Palsy: Presentation and Predictive Features During Infancy

PURPOSE To evaluate the presence and degree of glenohumeral dysplasia (GHD) in infants undergoing surgical exploration for neonatal brachial plexus palsy (NBPP) and to identify potential predictive factors of early maladaptive shoulder morphology. METHODS We included all consecutive patients with NBPP who underwent surgical exploration of their brachial plexus and who had a preoperative magnetic resonance imaging scan at our institution over a 3-year period. Demographic, therapy, and surgical data were collected. Imaging was reviewed for glenoid morphology, glenoid version, percent humeral head anterior to the scapula, and alpha angle. RESULTS Of 116 infants who presented to our institution during this 3-year period, 19 (16%) underwent surgical exploration and were included in the study. Median age at the time of the scan was 16 weeks (interquartile range, 14-46 weeks). Fourteen of 19 (74%) had GHD of Waters class 2 or increased malformation. Babies who had more severe palsies underwent earlier surgery and had less severe GHD at the time of surgery than did those with less severe palsies who had surgery later. Less severe GHD was associated with more severe palsies, as indicated by Narakas classification and number of root avulsions. Active external rotation was almost universally absent whereas other shoulder movements were present to varying degrees. More severe GHD was associated with greater total shoulder active range of motion and greater pectoralis major muscle mass. CONCLUSIONS Glenohumeral dysplasia occurs often and early in NBPP and may occur in the absence of restricted range of motion. Predictors include increasing age and factors related to muscular imbalance. As such, GHD likely affects the functional outcome that may be achieved with reinnervation, and early screening may improve outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic IV.