Cannabis Legalization and Resource Use for Ingestions by Young Children.

OBJECTIVE: In conjunction with widening legalization, there has been a rapid rise in unintentional cannabis ingestions in young children. We sought to determine if the legal status of recreational cannabis was associated with resource use in young children with cannabis poisoning. METHODS: This retrospective cross-sectional study of the Pediatric Health Information System included emergency department encounters between January 2016 and April 2023 for children <6 years of age with a diagnosis indicating cannabis ingestion. The primary exposure was recreational cannabis legalization status in the state in which the encounter occurred. We used logistic regression models to determine the association of recreational cannabis legality with resource utilization outcomes, adjusting for demographic covariates. RESULTS: We included 3649 children from 47 hospitals; 29% of encounters occurred in places in which recreational cannabis was legal. Compared with environments in which recreational cannabis was illegal, cannabis-legal locations had lower uses of advanced neuroimaging (24% vs 35%; adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI]: 0.55-0.77), lumbar puncture (1.6% vs 3.8%; aOR, 0.42; 95% CI: 0.24-0.70), ICU admission (7.9% vs 11%; aOR, 0.71; 95% CI: 0.54-0.93), and mechanical ventilation (0.8% vs 2.9%; aOR, 0.30; 95% CI: 0.14-0.58). Urine testing was more common in places in which recreational cannabis was legal (71% vs 58%; aOR, 1.87; 95% CI: 1.59-2.20). CONCLUSIONS: State-level legalization of recreational cannabis was associated with a significant decrease in the utilization of advanced medical resources in cases of cannabis intoxication in children. These findings suggest the need for a focus on policies and procedures to minimize invasive testing in cases of cannabis intoxication in children.

Association between positive blood culture and clinical outcomes among children treated for sepsis in the emergency department.

OBJECTIVE: Among children treated for sepsis in a pediatric emergency department (ED), compare clinical features and outcomes between those with blood cultures positive versus negative for a bacterial pathogen. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric emergency department (ED) at a quaternary pediatric care center. PATIENTS: Children aged 0-18 years treated for sepsis defined by the Children's Hospital Association's Improving Pediatric Sepsis Outcomes (IPSO) definition. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 1307 patients treated for sepsis during the study period, of which 117 (9.0%) had blood cultures positive for a bacterial pathogen. Of children with blood culture positive sepsis, 62 (53.0%) had organ dysfunction compared to 514 (43.2%) with culture negative sepsis (adjusted odds ratio 1.56, 95% confidence interval (CI) 1.04-2.34, adjusting for age, high risk medical conditions, and time to antibiotics). Children with blood culture positive sepsis had a larger base deficit, -4 vs -1 (p < 0.01), and higher procalcitonin, 3.84 vs 0.56 ng/mL (p < 0.01). CONCLUSIONS: Children meeting the IPSO Sepsis definition with blood culture positive for a bacterial pathogen have higher rates of organ dysfunction than those who are culture negative, although our 9% rate of blood culture positivity is lower than previously cited literature from the pediatric intensive care unit.

Asthmalitis? Diagnostic Variability of Asthma and Bronchiolitis in Children <24 Months.

BACKGROUND AND OBJECTIVES: Bronchiolitis and asthma have similar acute clinical presentations in young children yet have opposing treatment recommendations. We aimed to assess the role of age and other factors in the diagnosis of bronchiolitis and asthma in children <24 months of age. METHODS: We conducted a retrospective cross-sectional analysis of the Pediatric Health Information System database. We included children aged <2 years diagnosed with bronchiolitis, asthma, wheeze, or bronchospasm in emergency department or hospital encounters from 2017 to 2021. We described variation by age and between institutions. We used mixed-effects models to assess factors associated with a non-bronchiolitis diagnosis in children 12 to 23 months of age. RESULTS: We included 554 158 encounters from 42 hospitals. Bronchiolitis made up 98% of encounters for children <3 months of age, whereas asthma diagnoses increased with age and were included in 44% of encounters at 23 months of age. Diagnosis patterns varied widely between hospitals. In children 12 to 23 months of age, the odds of a non-bronchiolitis diagnosis increased with month of age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.12-1.13), male sex (OR 1.37, 95% CI 1.35-1.40), non-Hispanic Black race (OR 1.54, 95% CI 1.50-1.58), number of previous encounters (OR 2.73, 95% CI 2.61-2.86, for 3 or more encounters), and previous albuterol use (OR 2.24, 95% CI 2.16-2.32). CONCLUSIONS: Non-bronchiolitis diagnoses and the use of inhaled bronchodilators and systemic steroids for acute wheezing respiratory illness increase with month of age in children aged 0 to 23 months. Better definitions of clinical phenotypes of bronchiolitis and asthma would allow for more appropriate treatment in acute care settings, particularly in children 12 to 23 months of age.

Quality Improvement to Reduce High-Flow Nasal Cannula Overuse in Children With Bronchiolitis.

BACKGROUND: High-flow nasal cannula oxygen therapy (HFNC) is increasingly used to treat bronchiolitis. However, HFNC has not reduced time on supplemental oxygen, length of stay (LOS), or ICU admission. Our objective was to reduce HFNC use in children admitted for bronchiolitis from 41% to 20% over 2 years. METHODS: Using quality improvement methods, our multidisciplinary team formulated key drivers, including standardization of HFNC use, effective communication, knowledgeable staff, engaged providers and families, data transparency, and high-value care focus. Interventions included: (1) standardized HFNC initiation criteria, (2) staff education, (3) real-time feedback to providers, (4) a script for providers to use with families about expectations during admission, (5) team huddle for patients admitted on HFNC to discuss necessity, and (6) distribution of a bronchiolitis toolkit. We used statistical process control charts to track the percentage of children with bronchiolitis who received HFNC. Data were compared with a comparison institution not actively involved in quality improvement work around HFNC use to ensure improvements were not secondary to the COVID-19 pandemic alone. RESULTS: Over 10 months of interventions, we saw a decrease in HFNC use for patients admitted with bronchiolitis from 41% to 22%, which was sustained for >12 months. There was no change in HFNC use at the comparison institution. The overall mean LOS for children with bronchiolitis decreased from 60 to 45 hours. CONCLUSIONS: We successfully reduced HFNC use in children with bronchiolitis, improving delivery of high-value and evidence-based care. This reduction was associated with a 25% decrease in LOS.

Risk of Bacteremia in Febrile Children and Young Adults With Sickle Cell Disease in a Multicenter Emergency Department Cohort.

Importance: Bacteremia is a major cause of morbidity and mortality in children and young adults with sickle cell disease (SCD), but among those presenting to the emergency department (ED) with fever, the absolute risk of, risk factors associated with, and outcomes of bacteremia are poorly defined. Objective: To obtain contemporary data on the absolute risk of, risk factors associated with, and outcomes associated with bacteremia in children and young adults with SCD presenting to the ED with fever. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted of individuals with SCD younger than 22 years (young adults) presenting to EDs within the Pediatric Health Information Systems database from January 1, 2016, to December 31, 2021, with fever (identified by diagnostic codes for fever or the collection of blood samples for cultures and intravenous antibiotic administration). Data analysis was performed from May 17 to December 15, 2022. Main Outcomes and Measures: The risk of bacteremia (defined by diagnostic coding) was identified in these children and young adults, and univariate analyses and multivariable regression were used to examine patient-level factors and bacteremia. Results: A total of 35 548 encounters representing 11 181 individual patients from 36 hospitals were evaluated. The median age of the cohort was 6.17 (IQR, 2.36-12.11) years and 52.9% were male. Bacteremia was present in 405 encounters (1.1%, 95% CI, 1.05%-1.26%). A history of bacteremia, osteomyelitis, stroke, central line-associated bloodstream infection (CLABSI), central venous catheter, or apheresis was associated with the diagnosis of bacteremia, while age, sex, hemoglobin SC genotype, and race and ethnicity were not. In the multivariable analysis, individuals with a history of bacteremia (odds ratio [OR], 1.36; 95% CI, 1.01-1.83), CLABSI (OR, 6.39; 95% CI, 3.02-13.52), and apheresis (OR, 1.77; 95% CI, 1.22-2.55) had higher odds of bacteremia. Conclusions and Relevance: The findings of this large cohort study suggest that bacteremia in children and young adults with SCD presenting with fever is rare. A history of invasive bacterial infection, CLABSI, or a central line appears to be associated with bacteremia, while age and SCD genotype are not.

The Success of Resident-Associated Lumbar Punctures at a Large, Single-Center Children's Hospital.

OBJECTIVES: The frequency of lumbar punctures (LPs) has declined across US children's hospitals over the past decade, potentially decreasing procedural learning opportunities for pediatric resident trainees. Our study sought to determine whether the proportion of successful LPs performed by our pediatric residents has significantly changed over time. METHODS: This study is a single-center retrospective study to evaluate our pediatric resident LP success. We evaluated our primary outcome, proportion of overall LP success over time, using linear regression. We similarly used linear regression for proportion of successful resident-associated LPs over time. We calculated the median number of LPs of all pediatric residents during the study period. RESULTS: We analyzed 3143 LPs from April 2012 to December 2019. Both the overall number of LPs performed and the proportion of LPs that were successful have not significantly changed over an 8-year period ( P > 0.05, P > 0.05). Similarly, the number of our resident-associated LPs and the proportion of successful resident-associated LPs have not changed over the study period ( P > 0.05, P > 0.05). Our pediatric residents performed a median of 3 LPs (interquartile range: 2-4) in the pediatric emergency department (PED) over residency. CONCLUSIONS: Despite national trends showing decreased LP rates at pediatric hospitals, we demonstrated stable proportions of LPs and success by our pediatric residents. Pediatric residents perform a relatively low number of LPs in the PED setting alone. Future research is needed to demonstrate whether these overall low numbers in the PED translate to procedural competency after residency graduation.

Variation in Emergency Department Use of Racemic Epinephrine and Associated Outcomes for Croup.

OBJECTIVES: Racemic epinephrine (RE) is commonly administered for croup in the emergency department (ED). Our objectives were to examine variation in RE use between EDs, to determine whether ED variation in RE use is associated with hospital or patient factors, and to evaluate the associations between the rates of hospital-specific ED RE use and patient outcomes. METHODS: We performed a retrospective cohort study using the Pediatric Heath Information System of children aged 3 months to 10 years with croup in the ED. We used mixed-effects regression to calculate risk-standardized proportions of patients receiving RE in each ED and to analyze the relationship between risk-standardized institutional RE use and individual patient odds of hospital admission, ICU admission, and ED revisits. RESULTS: We analyzed 231 683 patient visits from 39 hospitals. ED administration of RE varied from 14% to 48% of visits (median, 24.5%; interquartile range, 20.0%-27.8%). A total of 8.6% of patients were hospitalized and 1% were admitted to the ICU. After standardizing for case mix and site effects, increasing ED use of RE per site was associated with increasing patient odds of hospital admission (odds ratio [OR], 1.39-95%; confidence interval [CI], 1.01-1.91), but not ICU admission (OR, 1.39; 95% CI, 0.99-1.97) or ED revisit (OR, 1.00; 95% CI, 0.92-1.09). CONCLUSIONS: In this large, observational study, RE administration varied widely across EDs. Increased RE use by site was associated with increased odds of hospital admission for individual patients when controlling for patient factors. These results suggest further standardization of RE use in children with croup is warranted.

Diurnal Variation in Frequency and Severity of Croup in the Emergency Department.

BACKGROUND: Emergency department (ED) presentation for croup is thought to occur more often at night, but evidence for its diurnal variation is sparse. Our objectives were to describe the diurnal patterns of ED presentation in children with croup and to determine whether time of arrival associated with severe clinical outcomes. METHODS: We conducted a retrospective cohort study using the Pediatric Health Information System. We included children 3 months to 11 years of age with an ED encounter for croup from 2016 through 2020. We quantified ED encounters by arrival hour and used generalized linear mixed-effects models to determine association between arrival time and racemic epinephrine use, hospitalization, intensive care unit (ICU) admission, and revisits. RESULTS: There was considerable diurnal variation in ED visits for croup. A total of 126 186 children (60.1%) presented to the ED at night (between 8 pm and 8 am), and 83 763 children presented during the day (39.9%). Peak arrival time was 12:00 am (14 189 encounters) and the nadir was at 2:00 pm (5231 encounters). Children presenting during overnight hours had increased odds of the use of racemic epinephrine (odds ratio [OR] 1.33; 95% confidence interval [95% CI], 1.30-1.36), but reduced odds of hospitalization (OR 0.76; 95% CI, 0.73-0.78), ICU admission (OR 0.61; 95% CI, 0.58-0.68), and 3 day ED revisits (OR 0.86; 95% CI, 0.83-0.90). CONCLUSIONS: Children with croup present to the ED more commonly at night. Children presenting to the ED with croup at night have greater odds of being treated with racemic epinephrine, but reduced odds of hospitalization, ICU admission, and return visits.

Transient synovitis of the hip: Current practice and risk of misdiagnosis.

INTRODUCTION: Transient synovitis (TS) is a common and benign cause of hip pain in children, but must be distinguished from more serious entities such as septic arthritis, osteomyelitis, and pyomyositis. Our objectives were to determine the risk of missed bacterial musculoskeletal infection and rates of diagnostic testing in children diagnosed with TS. METHODS: We performed a cohort study using the Pediatric Heath Information System of children 1-10 years diagnosed with TS in the ED. We determined rates of missed bacterial musculoskeletal infection (defined as a new diagnosis of septic arthritis, osteomyelitis, or pyomyositis within 14 days of initial ED visit). We described the initial diagnostic evaluation and ED management of children diagnosed with TS and variability between sites. RESULTS: We analyzed 6419 encounters from 37 hospitals. 62 (1.0%, 95%CI: 0.7-1.2%) children were diagnosed with a missed bacterial musculoskeletal infection. Children with missed infection were younger than those without (median age 2.6 vs. 4.6 years, p < 0.01). Serum laboratory testing was performed in 76% of encounters with minimal variation across sites. There was significant variation in the rates of hip ultrasound by site (2 to 92%), which has increased in use over time (from 42% in 2016 to 62% in 2021). CONCLUSION: In this large observational study, missed bacterial musculoskeletal infection in children diagnosed with TS was rare but more common in younger children. The optimal combination of bloodwork and radiographic testing, especially ultrasound, to distinguish TS from more serious disease remains unclear.

Risk of malignancy following emergency department Bell's palsy diagnosis in children.

OBJECTIVE: To quantify the risk of malignancy following the emergency department (ED) diagnosis of Bell's Palsy (BP) using a large retrospective cohort. STUDY DESIGN: We performed a cohort study using the Pediatric Health Information System database. We included all children (6 months - 17 years) from 2011 to 2020 with an ED diagnosis of BP. We excluded children with previous neurologic chronic condition or malignancy diagnosed during or prior to the index visit. Our primary outcome was diagnosis of malignancy within 60 days following the index ED visit. We compared clinical characteristics between children with and without new-onset malignancy. RESULTS: Of 12,272 encounters for BP, 41 had a new oncologic diagnosis within 60 days (0.33%, 95% confidence interval [CI]: 0.25-0.45%). Median time to oncologic diagnosis was 22 days. Primary CNS malignancy (59%) and leukemia (17.1%) were the most common diagnoses. Younger children had a higher incidence of new oncologic diagnosis compared with older children. Incidences were 0.68% (95% CI 0.36-1.3%), 0.70% (95% CI 0.38-1.3%), 0.26% (95% CI 0.15-0.47%), and 0.21% (95% CI 0.12-0.37%) for children aged <2 years, 2-5 years, 6-11 years, and 12-17 years respectively. CONCLUSIONS: We found a small but potentially clinically significant rate of new-onset oncologic diagnosis within 60 days after BP diagnosis in the ED, especially in children younger than 5 years. Further studies of the diagnostic utility of laboratory testing or neuroimaging and the risk of empiric steroids in children with BP are needed.

Evidence-based Standardization of Constipation Management in the Emergency Department: A Quality Improvement Study.

Constipation is a common problem in pediatric patients. Abdominal radiographs (AXRs) are frequently obtained in the pediatric emergency department for diagnosis despite their poor reliability to rule out underlying pathology or prognostic ability to determine the degree of constipation. The goal of this quality improvement (QI) initiative was to standardize the diagnosis and management of constipation in the pediatric emergency department and urgent care in patients ages 6 months to 21 years and decrease AXR use by 20% and sustain this reduction for 12 months. METHODS: This prospective QI project involved a multidisciplinary team at a large urban pediatric tertiary care center. The study team constructed a key driver diagram and identified interventions, such as creating a standardized evaluation and management algorithm for constipation, using free open-access medical education platforms, incorporating the electronic medical record interface, and expanding educational conferences to include standardized approach and discharge instructions for patients with constipation across all acuity levels. The primary measure of AXR utilization was tracked overtime on a statistical process control chart to evaluate the impact of interventions. RESULTS: The percentage of visits for constipation that included an AXR decreased from a baseline of 49.6%-37.1%, a 25% reduction. Length-of-stay, return visits within 7 days, and inpatient admissions remained unchanged by the interventions. CONCLUSIONS: QI methodology successfully decreased AXR utilization in the evaluation of constipation across a broad spectrum of acuity levels. Further interventions may help to decrease the length of stay and further decrease AXR utilization.

High-Flow Nasal Cannula in Bronchiolitis at a Pediatric Emergency Department: Trends and Outcomes.

OBJECTIVES: Use of high-flow nasal cannula (HFNC) for bronchiolitis has increased, but data describing the current use and impact of this therapy are limited. Our objective with this study was to describe the use of HFNC for bronchiolitis in a pediatric emergency department (ED) from 2013 to 2019 and to explore associations with clinical outcomes. METHODS: This was a retrospective cohort study of children aged 2 to 24 months with the diagnosis of bronchiolitis. The primary outcome was HFNC initiation in the ED. Secondary outcomes included admission rate, ICU (PICU) admission, transfer to PICU from floor, and endotracheal intubation. An adjusted interrupted times series analysis was performed to analyze changes in rates of primary and secondary outcomes over time. RESULTS: In total 11 149 children met inclusion criteria; 902 (8.1%) were initiated on HFNC. The rate of HFNC initiation increased from 1.3% in 2012-2013 to 17.0% in 2018-2019 (P trend ≤ .001). Less than 30% of children initiated on HFNC were hypoxic. There were no significant changes over time in rates of hospital admission, PICU admission, or PICU transfer, adjusting for clinical severity, seasonality, and provider variation. Intubation rate increased over the study period. CONCLUSIONS: We found a 13-fold increase in HFNC use over a 6-year period with no evidence of improvement in clinically meaningful outcomes. Clinical benefit should be clearly defined before further expansion of the use of HFNC for bronchiolitis in the ED.

Factors Associated With Antibiotic Prescribing and Outcomes for Pediatric Pneumonia in the Emergency Department.

OBJECTIVES: Chest radiographs (CXRs) are often performed in children with respiratory illness to inform the decision to prescribe antibiotics. Our objective was to determine the factors associated with clinicians' plans to treat with antibiotics prior to knowledge of CXR results and the associations between preradiograph plans with antibiotic prescription and return to medical care. METHODS: Previously healthy children aged 3 months to 18 years with a CXR for suspected pneumonia were enrolled in a prospective cohort study in the emergency department. Our primary outcomes were antibiotic prescription or administration in the emergency department and medical care sought within 7 to 15 days after discharge. Inverse probability treatment weighting was used to limit bias due to treatment selection. Inverse probability treatment weighting was included in a logistic regression model estimating the association between the intention to give antibiotics and outcomes. RESULTS: Providers planned to prescribe antibiotics prior to CXR in 68 children (34.9%). There was no difference in the presence of radiographic pneumonia between those with and without a plan for antibiotics. Children who had a plan for antibiotics were more likely to receive antibiotics than those without (odds ratio [OR], 6.39; 95% confidence interval [CI], 3.7-11.0). This association was stronger than the association between radiographic pneumonia and antibiotic receipt (OR, 3.49; 95% CI, 1.98-6.14). Children prescribed antibiotics were more likely to seek care after discharge than children who were not (OR, 1.85; 95% CI, 1.13-3.05). CONCLUSIONS: Intention to prescribe antibiotics based on clinical impression was the strongest predictor of antibiotic prescription in our study. Prescribing antibiotics may lead to subsequent medical care after controlling for radiographic pneumonia.

Invasive Bacterial Infections in Afebrile Infants Diagnosed With Acute Otitis Media.

OBJECTIVES: To determine the prevalence of invasive bacterial infections (IBIs) and adverse events in afebrile infants with acute otitis media (AOM). METHODS: We conducted a 33-site cross-sectional study of afebrile infants ≤90 days of age with AOM seen in emergency departments from 2007 to 2017. Eligible infants were identified using emergency department diagnosis codes and confirmed by chart review. IBIs (bacteremia and meningitis) were determined by the growth of pathogenic bacteria in blood or cerebrospinal fluid (CSF) culture. Adverse events were defined as substantial complications resulting from or potentially associated with AOM. We used generalized linear mixed-effects models to identify factors associated with IBI diagnostic testing, controlling for site-level clustering effect. RESULTS: Of 5270 infants screened, 1637 met study criteria. None of the 278 (0%; 95% confidence interval [CI]: 0%-1.4%) infants with blood cultures had bacteremia; 0 of 102 (0%; 95% CI: 0%-3.6%) with CSF cultures had bacterial meningitis; 2 of 645 (0.3%; 95% CI: 0.1%-1.1%) infants with 30-day follow-up had adverse events, including lymphadenitis (1) and culture-negative sepsis (1). Diagnostic testing for IBI varied across sites and by age; overall, 278 (17.0%) had blood cultures, and 102 (6.2%) had CSF cultures obtained. Compared with infants 0 to 28 days old, older infants were less likely to have blood cultures (P < .001) or CSF cultures (P < .001) obtained. CONCLUSION: Afebrile infants with clinician-diagnosed AOM have a low prevalence of IBIs and adverse events; therefore, outpatient management without diagnostic testing may be reasonable.

Antibiotic Use and Outcomes in Children in the Emergency Department With Suspected Pneumonia.

BACKGROUND AND OBJECTIVES: Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED). METHODS: We performed a prospective cohort study of children (ages 3 months-18 years) who were discharged from the ED with suspected CAP. The primary exposure was antibiotic receipt or prescription. The primary outcome was treatment failure (ie, hospitalization after being discharged from the ED, return visit with antibiotic initiation or change, or antibiotic change within 7-15 days from the ED visit). The secondary outcomes included parent-reported quality-of-life measures. Propensity score matching was used to limit potential bias attributable to treatment selection between children who did and did not receive an antibiotic prescription. RESULTS: Of 337 eligible children, 294 were matched on the basis of propensity score. There was no statistical difference in treatment failure between children who received antibiotics and those who did not (odds ratio 1.0; 95% confidence interval 0.45-2.2). There was no difference in the proportion of children with return visits with hospitalization (3.4% with antibiotics versus 3.4% without), initiation and/or change of antibiotics (4.8% vs 6.1%), or parent-reported quality-of-life measures. CONCLUSIONS: Among children with suspected CAP, the outcomes were not statistically different between those who did and did not receive an antibiotic prescription.

A Novel Approach to Assessing Infants With Neonatal Abstinence Syndrome.

OBJECTIVES: Neonatal abstinence syndrome (NAS) is a growing problem and poses a significant burden on the health care system. The traditional Finnegan Neonatal Abstinence Scoring System (FNASS) assessment approach may lead to unnecessary opioid treatment of infants with NAS. We developed a novel assessment approach and describe its effect on the management of infants with NAS. METHODS: We retrospectively compared treatment decisions of 50 consecutive opioid-exposed infants managed on the inpatient unit at the Yale New Haven Children's Hospital. All infants had FNASS scores recorded every 2 to 6 hours but were managed by using the Eat, Sleep, Console (ESC) assessment approach. Actual treatment decisions made by using the ESC approach were compared with predicted treatment decisions based on recorded FNASS scores. The primary outcome was postnatal treatment with morphine. RESULTS: By using the ESC approach, 6 infants (12%) were treated with morphine compared with 31 infants (62%) predicted to be treated with morphine by using the FNASS approach (P < .001). The ESC approach started or increased morphine on 8 days (2.7%) compared with 76 days (25.7%) predicted by using the FNASS approach (P < .001). There were no readmissions or adverse events reported. CONCLUSIONS: Infants managed by using the ESC approach were treated with morphine significantly less frequently than they would have been by using the FNASS approach. The ESC approach is an effective method for the management of infants with NAS that limits pharmacologic treatment and may lead to substantial reductions in length of stay.

Mechanisms of disease: mitochondria as new therapeutic targets in diabetic neuropathy.

Diabetic neuropathy (DN) is the most common complication of diabetes mellitus, and it imposes a considerable burden on a patient's quality of life and the health-care system. Despite the prevalence and severity of DN, there are no effective treatments. Pathogenetic evidence suggests that DN is marked by degeneration of dorsal root ganglion (DRG) neurons in peripheral nerves, and that DRG mitochondria are particularly affected. DRG mitochondria are especially vulnerable because they are the origin of reactive oxygen species production in the hyperglycemic neuron. Accumulating evidence indicates that neuronal mitochondria are subject to damage at the level of their DNA, and their outer and inner membranes, and also via deregulation of mitochondrial fission and fusion proteins that control mitochondrial shape and number. This Review will survey the mechanisms of mitochondrial degeneration in the pathogenesis of DN, highlighting potential mitochondrial sites for therapeutic intervention.