Nine Seasons of a Bronchiolitis Observation Unit and Home Oxygen Therapy Protocol.

BACKGROUND: We implemented an observation unit and home oxygen therapy (OU-HOT) protocol at our children's hospital during the 2010-2011 winter season to facilitate earlier discharge of children hospitalized with bronchiolitis. An earlier study demonstrated substantial reductions in inpatient length of stay and costs in the first year after implementation. OBJECTIVE: Evaluate long-term reductions in length of stay and cost. DESIGN, SETTING, AND PARTICIPANTS: Interrupted time-series analysis, adjusting for patient demographic factors and disease severity. Participants were children aged 3 to 24 months and hospitalized with bronchiolitis from 2007 to 2019. INTERVENTION: OU-HOT protocol implementation. MAIN OUTCOME AND MEASURES: Hospital length of stay. Process measures were the percentage of patients discharged from the OU; percentage of patients discharged with HOT. Balancing measures were 7-day hospital revisit rates; annual per-population bronchiolitis admission rates. Secondary outcomes were inflation-adjusted cost per episode of care and discharges within 24 hours. RESULTS: A total of 7,116 patients met inclusion criteria. The OU-HOT protocol was associated with immediate decreases in mean length of stay (-30.6 hours; 95% CI, -37.1 to -24.2 hours) and mean cost per episode of care (-$4,181; 95% CI, -$4,829 to -$3,533). These findings were sustained for 9 years after implementation. Hospital revisit rates did not increase immediately (-1.1% immediate change; 95% CI, -1.8% to -0.4%), but a small increase in revisits was observed over time (change in slope 0.4% per season, 95% CI, 0.1%-0.8%). CONCLUSION: The OU-HOT protocol was associated with sustained reductions in length of stay and cost, representing a promising strategy to reduce the inpatient burden of bronchiolitis.

Comparative Seasonal Respiratory Virus Epidemic Timing in Utah.

Previous studies have found evidence of viral interference between seasonal respiratory viruses. Using laboratory-confirmed data from a Utah-based healthcare provider, Intermountain Health Care, we analyzed the time-specific patterns of respiratory syncytial virus (RSV), influenza A, influenza B, human metapneumovirus, rhinovirus, and enterovirus circulation from 2004 to 2018, using descriptive methods and wavelet analysis (n = 89,462) on a local level. The results showed that RSV virus dynamics in Utah were the most consistent of any of the viruses studied, and that the other seasonal viruses were generally in synchrony with RSV, except for enterovirus (which mostly occurs late summer to early fall) and influenza A and B during pandemic years.

Clinical and Molecular Epidemiology of Invasive Haemophilus influenzae Serotype a Infections in Utah Children.

BACKGROUND: Following widespread use of the Haemophilus influenzae serotype b (Hib) vaccine, H. influenzae serotype a (Hia) has emerged as an important pathogen in children in some regions. We describe the clinical features and molecular epidemiology of invasive Hia disease in children in Utah over an 11-year period. METHODS: We identified cases of invasive Hia disease, defined as detection of Hia from a normally sterile site, in children aged <18 years from Utah between 2007 and 2017. Medical records were reviewed to determine demographic characteristics and clinical outcomes. Available Hia isolates were genotyped using multilocus sequence typing, and phylogenetic division was determined using sodC polymerase chain reaction. Presence of the putative virulence-associated IS1016-bexA duplication-deletion was evaluated. RESULTS: We identified 51 children with invasive Hia. The average annual incidence was 1.7 cases per 100 000 children aged <5 years; 4.8 cases per 100 000 children aged <1 year. The median age was 11.3 months. The most common clinical presentation was meningitis (53%), followed by pneumonia (14%) and septic arthritis (14%). Twenty-two children (43%) required admission to an intensive care unit; 1 died. Sequence type (ST) 62, phylogenetic division II isolates caused 75% (21/28) of disease. No isolates contained the virulence-associated IS1016-bexA duplication-deletion. CONCLUSIONS: Hia is a significant cause of severe invasive bacterial infection in Utah. The majority of infections were caused by ST62 isolates, a phylogenetic division II Hia type that lacks the IS1016-bexA duplication-deletion. Hia ST62 has not been commonly reported elsewhere, suggesting a unique molecular epidemiology in our population.

Midturbinate Swabs Are Comparable to Nasopharyngeal Swabs for Quantitative Detection of Respiratory Syncytial Virus in Infants.

Nasopharyngeal (NP) swabs are generally used to detect respiratory syncytial virus (RSV) in infants. However, midturbinate (MT) swabs may provide comparable results. In this study, we enrolled hospitalized infants aged <24 months with RSV and collected NP and MT swabs. The resulting viral loads measured by real-time reverse-transcription quantitative polymerase chain reaction were similar. Most parents preferred MT swabs over NP swabs.

Autism Spectrum Disorder and Neonatal Serum Magnesium Levels in Preterm Infants.

Premature birth is associated with increased risk of autism spectrum disorder. Antenatal maternal magnesium administration is known to reduce subsequent risk of cerebral palsy including among premature infants, suggesting a potentially broader neuroprotective role for magnesium. Our objective was to determine whether magnesium could be protective against autism spectrum disorders in premature infants. A cohort of 4855 preterm children was identified, magnesium levels from 24 to 48 hours of life recorded, and subsequent autism spectrum disorder status determined. Adjusted relative risk of autism spectrum disorder with each 1 mg/dL increase in neonatal magnesium level was 1.15 (95% confidence interval: 0.86-1.53). Analysis of variance indicated that magnesium levels varied by gestational age and maternal antenatal magnesium supplementation, but not autism spectrum disorder status (F1,4824 = 1.43, P = .23). We found that neonatal magnesium levels were not associated with decreased autism spectrum disorder risk. Future research into autism spectrum disorder risks and treatments in premature infants is needed.

Short-Term Elevation of Fine Particulate Matter Air Pollution and Acute Lower Respiratory Infection.

RATIONALE: Nearly 60% of U.S. children live in counties with particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5) concentrations above air quality standards. Understanding the relationship between ambient air pollution exposure and health outcomes informs actions to reduce exposure and disease risk. OBJECTIVES: To evaluate the association between ambient PM2.5 levels and healthcare encounters for acute lower respiratory infection (ALRI). METHODS: Using an observational case-crossover design, subjects (n = 146,397) were studied if they had an ALRI diagnosis and resided on Utah's Wasatch Front. PM2.5 air pollution concentrations were measured using community-based air quality monitors between 1999 and 2016. Odds ratios for ALRI healthcare encounters were calculated after stratification by ages 0-2, 3-17, and 18 or more years. MEASUREMENTS AND MAIN RESULTS: Approximately 77% (n = 112,467) of subjects were 0-2 years of age. The odds of ALRI encounter for these young children increased within 1 week of elevated PM2.5 and peaked after 3 weeks with a cumulative 28-day odds ratio of 1.15 per +10 µg/m3 (95% confidence interval, 1.12-1.19). ALRI encounters with diagnosed and laboratory-confirmed respiratory syncytial virus and influenza increased following elevated ambient PM2.5 levels. Similar elevated odds for ALRI were also observed for older children, although the number of events and precision of estimates were much lower. CONCLUSIONS: In this large sample of urban/suburban patients, short-term exposure to elevated PM2.5 air pollution was associated with greater healthcare use for ALRI in young children, older children, and adults. Further exploration is needed of causal interactions between PM2.5 and ALRI.

Rhinovirus in Febrile Infants and Risk of Bacterial Infection.

BACKGROUND: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown. METHODS: Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected. RESULTS: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]). CONCLUSIONS: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age.

Predicting tacrolimus concentrations in children receiving a heart transplant using a population pharmacokinetic model.

OBJECTIVE: Immunosuppressant therapy plays a pivotal role in transplant success and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to exhibit significant pharmacological interpatient and intrapatient variability. This variability necessitates the collection of serial trough concentrations to ensure that the drug remains within therapeutic range. The objective of this study was to build a population pharmacokinetic (PK) model and use it to determine the minimum number of trough samples needed to guide the prediction of an individual's future concentrations. DESIGN SETTING AND PATIENTS: Retrospective data from 48 children who received tacrolimus as inpatients at Primary Children's Hospital in Salt Lake City, Utah were included in the study. Data were collected within the first 6 weeks after heart transplant. OUTCOME MEASURES: Data analysis used population PK modelling techniques in NONMEM. Predictive ability of the model was determined using median prediction error (MPE, a measure of bias) and median absolute prediction error (MAPE, a measure of accuracy). Of the 48 children in the study, 30 were used in the model building dataset, and 18 in the model validation dataset. RESULTS: Concentrations ranged between 1.5 and 37.7 µg/L across all collected data, with only 40% of those concentrations falling within the targeted concentration range (12 to 16 µg/L). The final population PK model contained the impact of age (on volume), creatinine clearance (on elimination rate) and fluconazole use (on elimination rate) as covariates. Our analysis demonstrated that as few as three concentrations could be used to predict future concentrations, with negligible bias (MPE (95% CI)=0.10% (-2.9% to 3.7%)) and good accuracy (MAPE (95% CI)=24.1% (19.7% to 27.7%)). CONCLUSIONS: The use of PK in dose guidance has the potential to provide significant benefits to clinical care, including dose optimisation during the early stages of therapy, and the potential to limit the need for frequent drug monitoring.

Infectious Etiologies and Patient Outcomes in Pediatric Septic Shock.

BACKGROUND: Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. METHODS: We evaluated a retrospective cohort of children (age <19) treated in our emergency department (ED) for septic shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in ≤1 hour and (2) receipt of appropriate antibiotics in ≤1 hour. The primary outcome was development of new or progressive multiple system organ dysfunction syndrome (NP-MODS). The secondary outcome was mortality. RESULTS: Among 321 patients admitted to intensive care, 48% (n = 153) received empiric antibiotics in ≤1 hour. These patients were more ill at presentation with significantly greater median pediatric index of mortality 2 (PIM2) scores and were more likely to receive recommended resuscitation in the ED (61% vs 14%); however, rates of NP-MODS (9% vs 12%) and hospital mortality (7% vs 4%) were similar to those treated later. Early, appropriate antibiotics were administered to 33% (n = 67) of patients with identified or suspected bacterial infection. These patients had significantly greater PIM2 scores but similar rates of NP-MODS (15% vs 15%) and hospital mortality (10% vs 6%) to those treated later. CONCLUSIONS: Critically ill children with septic shock treated in a children's hospital ED who received antibiotics in ≤1 hour were significantly more severely ill than those treated later, but they did not have increased risk of NP-MODS or death.

AUC-Guided Vancomycin Dosing in Adolescent Patients With Suspected Sepsis.

Vancomycin is a first-line treatment for ß-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013. Population PK modeling was performed in NONMEM 7.3. Vancomycin PK was well described with a 1-compartment model that identified both body weight (WT) and creatinine clearance (CRCL) as covariates significantly impacting vancomycin disposition. The model was then utilized to determine dosing strategies that achieved the targeted area under the 24-hour time curve vs minimum inhibitory concentration (AUC0-24 /MIC) ratio of ≥400. Additionally, these data were correlated with minimum steady-state concentrations (Css,min ) to find an acceptable target trough concentration range in adolescents. This analysis demonstrated that Css,min ranging from 10 to 12.5 mg/L were highly predictive of achieving an AUC0-24 /MIC ≥400 when the MIC was ≤1 mg/L. These results suggest that the target trough concentration for adolescents may be lower than that for adults.

Detection of 23 Gastrointestinal Pathogens Among Children Who Present With Diarrhea.

BACKGROUND: Diarrheal diseases are a major cause of ambulatory care visits and hospitalizations among children. Because of overlapping signs and symptoms and expensive and inefficient testing methods, the etiology of pediatric diarrhea is rarely established. METHODS: We identified children <18 years of age who were evaluated for diarrhea at Primary Children's Hospital in Salt Lake City, Utah, between October 2010 and September 2012. Stool specimens submitted for testing were evaluated by using the FilmArray gastrointestinal diagnostic system, which is a rapid multiplex polymerase chain reaction platform that can simultaneously detect 23 bacterial, viral, and protozoal agents. RESULTS: A pathogen was detected in 561 (52%) of 1089 diarrheal episodes. The most commonly detected pathogens included toxigenic Clostridium difficile (16%), diarrheagenic Escherichia coli (15%), norovirus GI/GII (11%), and adenovirus F 40/41 (7%). Shiga toxin-producing E coli were detected in 43 (4%) specimens. Multiple pathogens were identified in 160 (15%) specimens. Viral pathogens (norovirus, adenovirus, rotavirus, and sapovirus) were more common among children <5 years old than among those 5 to 17 years old (38% vs 16%, respectively; P < .001). Bacterial pathogens were identified most commonly in children 2 to 4 years of age. Children with 1 or more underlying chronic medical conditions were less likely to have a pathogen identified than those without a chronic medical condition (45% vs 60%, respectively; P < .01). Viral pathogens were detected more commonly in the winter, whereas bacterial pathogens were detected more commonly in the summer. CONCLUSIONS: Toxigenic C difficile, diarrheagenic E coli, and norovirus were the leading organisms detected among these children with diarrhea. Viral pathogens are identified frequently among young children with acute gastroenteritis.

Comprehensive population-based determination of pediatric multiple sclerosis health care costs.

OBJECTIVE: To determine the health care costs associated with pediatric multiple sclerosis (MS). METHODS: We performed a retrospective analysis of all patients with MS 18 years of age or younger who were diagnosed or treated between 2002 and 2012 in a population-based cohort. Demographics and health care costs were extracted from the Intermountain Healthcare Enterprise Data Warehouse. Patients were divided into high-cost (>84th percentile) and low-cost groups and differences in health care utilization between the groups were analyzed. RESULTS: Fifty-seven pediatric patients with MS were identified. Health care costs for the cohort totaled more than $1.5 million over the 10-year period, with the top 16th percentile of patients contributing nearly two-thirds. Outpatient visits represented the majority of health care encounters and expenditures, accounting for 83.1% of total costs. Costs per encounter were highest for inpatient stays, averaging $2,924 per stay. CONCLUSIONS: The burden of health care expenses for pediatric patients with MS is significant. Expenditures related to outpatient visits were the largest contributor to costs, but inpatient stays were the most costly per encounter. A small proportion of patients incurred the bulk of costs and spent significantly more time receiving care compared to the majority of patients. Avoidance of inpatient treatment and efficient outpatient management are potential areas for health care cost reduction and improvement in care.

Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines and PICU Patient Outcomes.

OBJECTIVES: The Surviving Sepsis Campaign recommends rapid recognition and treatment of severe sepsis and septic shock. Few reports have evaluated the impact of these recommendations in pediatrics. We sought to determine if outcomes in patients who received initial care compliant with the Surviving Sepsis Campaign time goals differed from those treated more slowly. DESIGN: Single center retrospective cohort study. SETTING: Emergency department and PICU at an academic children's hospital. PATIENTS: Three hundred twenty-one patients treated for septic shock in the emergency department and admitted directly to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure was receipt of emergency department care compliant with the Surviving Sepsis Campaign recommendations (delivery of IV fluids, IV antibiotics, and vasoactive infusions within 1 hr of shock recognition). The primary outcome was development of new or progressive multiple organ dysfunction syndrome. Secondary outcomes included mortality, need for mechanical ventilation or vasoactive medications, and hospital and PICU length of stay. Of the 321 children studied, 117 received Surviving Sepsis Campaign compliant care in the emergency department and 204 did not. New or progressive multiple organ dysfunction syndrome developed in nine of the patients (7.7%) who received Surviving Sepsis Campaign compliant care and 25 (12.3%) who did not (p = 0.26). There were 17 deaths; overall mortality rate was 5%. There were no significant differences between groups in any of the secondary outcomes. Although only 36% of patients met the Surviving Sepsis Campaign guideline recommendation of bundled care within 1 hour of shock recognition, 75% of patients received the recommended interventions in less than 3 hours. CONCLUSIONS: Treatment for pediatric septic shock in compliance with the Surviving Sepsis Campaign recommendations was not associated with better outcomes compared with children whose initial therapies in the emergency department were administered more slowly. However, all patients were treated rapidly and we report low morbidity and mortality. This underscores the importance of rapid recognition and treatment of septic shock.

Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates.

BACKGROUND: This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period. METHODS: A retrospective observational study was conducted in preterm neonates who received caffeine citrate therapy for apnea of prematurity and had TDM done in the post-extubation period between January 2006 and October 2011. The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored. RESULTS: A total of 177 blood samples were obtained from 115 preterm neonates with a median (range) gestational age of 29 (24 - 33) weeks and birth weight of 1230 (607 - 2304) kg. Caffeine citrate therapy was initiated at a median (interquartile range) postnatal age of 1 (1 - 3) day and TDM was performed at a postnatal age of 15 (10 - 24) days. No direct correlations were found between respiratory rate or apneic episodes and caffeine serum concentrations; however, heart rate and caffeine serum concentrations were significantly correlated (p < 0.05). Dosing regimen of 40/5 mg/kg q12h (loading dose/maintenance dose, time interval) led to similar endotracheal re-intubation rate but increased percentage of patients experiencing tachycardia compared to the standard regimen of 20/5 mg/kg q24h (44.7 % vs 10.2 %, p < 0.001). CONCLUSION: Based on this retrospective study, no correlation between episodes of apnea and caffeine serum concentrations was found in neonates who had TDM of caffeine citrate therapy in the post-extubation period, whereas a significant association between tachycardia and concentrations existed. Notwithstanding the absence of severe adverse reactions, TDM should be considered in critically ill neonates with unexplained adverse effects, such as tachycardia.

Initial Presentation of Neonatal Herpes Simplex Virus Infection.

OBJECTIVE: To inform the decision to test and empirically treat for herpes simplex virus (HSV) by describing the initial clinical presentation and laboratory findings of infants with a confirmed diagnosis of neonatal HSV. STUDY DESIGN: This is a retrospective case series performed at 2 pediatric tertiary care centers. Infants who developed symptoms prior to 42 days of age with laboratory confirmed HSV from 2002 through 2012 were included. We excluded infants <34 weeks gestation, those who developed illness before discharge from their birth hospital, and those who developed symptoms after 42 days of age. RESULTS: We identified 49 infants with HSV meeting these criteria. Most infants (43/49, 88%) came to medical attention at ≤28 days. Of 49 infants, 22 (45%) had disseminated, 16 (33%) central nervous system, and 10 (20%) skin, eye, mouth HSV disease. Eight infants (16%) had nonspecific presentations without the classic signs of seizure, vesicular rash, or critical illness (intensive care admission). All infants with nonspecific presentation were ≤14 days, had cerebrospinal fluid pleocytosis, or both. CONCLUSIONS: The majority of infants with HSV (84%) presented with seizure, vesicular rash, or critical illness. A subset of patients (16%) lacked classic signs at hospitalization; most manifested signs suggestive of HSV within 24 hours. Further studies are needed to validate the risk factors identified in this study including age <14 days and cerebrospinal fluid pleocytosis at presentation.

A propensity-matched cohort study of vancomycin-associated nephrotoxicity in neonates.

BACKGROUND: The incidence of nephrotoxicity among vancomycin-treated neonates has been reported to range from 2% to 20%. These widely varying estimates have led to confusion and controversy regarding the safety of vancomycin among neonates. OBJECTIVE: Evaluate the incidence of nephrotoxicity among neonates receiving vancomycin concomitantly with gentamicin. DESIGN: Retrospective observational cohort study using propensity score matching to provide covariate balance between neonates who did or did not receive vancomycin based on factors known to be related to the development of renal dysfunction. SETTING: Hospitals (n=22) throughout the Intermountain West, including a quaternary care children's hospital. PATIENTS: Neonates ≤44 postmenstrual weeks (median gestational age: 31 (IQR 28-36) weeks) receiving intravenous gentamicin with or without exposure to vancomycin from January 2006 to December 2012. MAIN OUTCOME MEASURES: Nephrotoxicity based on the modified Acute Kidney Injury Network criteria for acute kidney injury (AKI) or serum creatinine concentration ≥1.5 mg/dL persisting for ≥48 h. RESULTS: The final cohort was comprised of 1066 neonates (533 receiving vancomycin and gentamicin vs 533 receiving gentamicin). In a propensity score-matched cohort that was well balanced across 16 covariates, AKI was not associated with vancomycin use (16 neonates receiving vancomycin vs 7 controls experienced AKI; OR 1.5; 95% CI 0.6 to 4.0). However, the presence of a patent ductus arteriosus, concomitant non-steroidal anti-inflammatory drug use, ≥1 positive blood cultures, low birth weight and higher severity of illness and risk of mortality scores were associated with an increased risk of nephrotoxicity. CONCLUSIONS: These results corroborate several earlier reports and much anecdotal evidence describing the infrequent occurrence of nephrotoxicity in neonates receiving concomitant vancomycin and gentamicin.

Tocolysis for Women With Early Spontaneous Preterm Labor and Advanced Cervical Dilation.

OBJECTIVE: To characterize tocolytic use and examine perinatal outcomes among women presenting very preterm with spontaneous labor and cervical dilation 4 cm or greater. METHODS: This was a retrospective cohort study. Data from January 2000 to June 2011 in a single health care system were reviewed. Women with singleton, nonanomalous fetuses and preterm labor with intact membranes between 23 and 32 weeks of gestation who had cervical dilation 4 cm or greater and less than 8 cm at admission were included. Women receiving one or more tocolytics (magnesium sulfate, indomethacin, or nifedipine) were compared with those who did not receive tocolysis. The primary outcome was composite major neonatal morbidity. RESULTS: Two hundred ninety-seven women were included; 233 (78.5%) received at least one tocolytic. Women receiving tocolysis were slightly less dilated (median 5 compared with 6 cm, P<.001) at presentation and were more likely to receive at least a partial course of corticosteroids (88.4% compared with 56.3%, P<.001). Initial composite severe neonatal morbidity rates were similar (41.6% compared with 43.8%, P=.761) regardless of tocolytic administration. Those receiving tocolysis were significantly more likely to be pregnant at least 48 hours after admission (23.6% compared with 7.8%, P=.005), but a similar proportion delivered within 7 days of admission (94.8% compared with 95.3%, P>.99), and delivery gestational ages were similar (28.9 compared with 29.2 weeks, P=.408). The incidence of chorioamnionitis and postpartum endometritis was similar between groups. CONCLUSION: The majority of women presenting very preterm with advanced cervical dilation received tocolysis. Although tocolysis administration increased the likelihood of achieving at least 48 hours of latency, initial neonatal outcomes were similar. LEVEL OF EVIDENCE: II.

Costs of the diagnostic odyssey in children with inherited leukodystrophies.

OBJECTIVES: Our objective was to determine the extent of testing and costs solely related to diagnosis (the diagnostic odyssey) in a cohort of children with inherited leukodystrophies. METHODS: We determined all inpatient and outpatient laboratory testing, including brain MRIs obtained for the purpose of diagnosis, over an 8-year time period in a retrospective population cohort of children with inherited leukodystrophies. Costs were determined from an activity-based cost accounting system and were standardized to 2013 constant US dollars. RESULTS: Each patient had on average 20 tests (range 2-42 tests), with costs of $4,200 (range $357-$15,611). Diagnostic yield plateaued after 25 tests, and costs increased significantly after 32 tests. Fifty-three percent of patients were diagnosed in 20 or fewer tests, compared with 17% if more than 20 tests were performed. CONCLUSIONS: Our findings provide details on the amount and costs of testing in children who often undergo a diagnostic odyssey. Our results suggest that diagnostic testing is a relatively modest contributor to the overall health care costs in patients with leukodystrophy, and offer insights into the diagnostic odyssey of children with neurologic impairment.

Targeted leukodystrophy diagnosis based on charges and yields for testing.

Inherited leukodystrophies are a group of neurological disorders with significant morbidity and mortality. Children and their families can experience lengthy diagnostic odysseys; however, there is no data on the charges related to testing for diagnosis in leukodystrophy patients, compared to approaches using next-generation sequencing (NGS). Our objective was to determine charges related to the determination of diagnosis, and overall yield of diagnostic testing, for leukodystrophy patients. We determined and quantified all inpatient and outpatient lab testing, including brain MRIs, obtained for the purpose of diagnosis, in a retrospective population cohort of children with inherited leukodystrophies. Each patient had average charges of $8,231 (range $543-26,437) for diagnostic testing. Overall charges related to diagnosis for the entire cohort was $526,794. A final etiological diagnosis was determined in 34% of patients. In those in whom a specific diagnosis was determined, average time to diagnosis was 1.4 years. If NGS on the entire cohort had been performed instead, charges would have been ∼$359,600 (at $5,800/patient). Alternatively, a two-tier approach consisting of first, biochemical testing (serum very-long chain fatty acids and leukocyte lysosomal enzyme testing), and then with NGS for remaining undiagnosed patients, would have resulted in total cohort charges of $361,309. We have determined the charges directly associated with diagnostic testing in a population cohort of children with leukodystrophy. We conclude that appropriately incorporating NGS into diagnostic algorithms could lower charges; reduce time to diagnosis; and reduce amount of testing.