IMPORTANCEOpioids are frequently prescribed to children and adolescents after surgery. Prescription opioid misuse is associated with high-risk behavior in youth. Evidence-based guidelines for opioid prescribing practices in children are lacking.OBJECTIVE To assemble a multidisciplinary team of health care experts and leaders in opioid stewardship, review current literature regarding opioid use and risks unique to pediatric populations, and develop a broad framework for evidence-based opioid prescribing guidelines for children who require surgery.EVIDENCE REVIEW Reviews of relevant literature were performed including all English-language articles published from January 1, 1988, to February 28, 2019, found via searches of the PubMed (MEDLINE), CINAHL, Embase, and Cochrane databases. Pediatric was defined as children younger than 18 years. Animal and experimental studies, case reports, review articles, and editorials were excluded. Selected articles were graded using tools from the Oxford Centre for Evidence-based Medicine 2011 levels of evidence. The Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument was applied throughout guideline creation. Consensus was determined using a modified Delphi technique.FINDINGS Overall, 14 574 articles were screened for inclusion, with 217 unique articles included for qualitative synthesis. Twenty guideline statements were generated from a 2-day in-person meeting and subsequently reviewed, edited, and endorsed externally by pediatric surgical specialists, the American Pediatric Surgery Association Board of Governors, the American Academy of Pediatrics Section on Surgery Executive Committee, and the American College of Surgeons Board of Regents. Review of the literature and guideline statements underscored 3 primary themes: (1) health care professionals caring for children who require surgery must recognize the risks of opioid misuse associated with prescription opioids, (2) nonopioid analgesic use should be optimized in the perioperative period, and (3) patient and family education regarding perioperative pain management and safe opioid use practices must occur both before and after surgery.CONCLUSIONS AND RELEVANCE These are the first opioid-prescribing guidelines to address the unique needs of children who require surgery. Health care professionals caring for children and adolescents in the perioperative period should optimize pain management and minimize risks associated with opioid use by engaging patients and families in opioid stewardship efforts.

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BACKGROUND AND OBJECTIVES: Despite previous studies demonstrating no difference in mortality or morbidity, the various surgical approaches for necrotizing enterocolitis (NEC) in infants have not been evaluated economically. Our goal was to compare total in-hospital cost and mortality by using propensity score-matched infants treated with peritoneal drainage alone, peritoneal drainage followed by laparotomy, or laparotomy alone for surgical NEC. RESULTS: Successful propensity score matching was performed with 699 infants (peritoneal drainage, n = 101; peritoneal drainage followed by laparotomy, n = 172; and laparotomy, n = 426). Average adjusted cost for peritoneal drainage followed by laparotomy was $ CONCLUSIONS: Propensity score-matched analysis of surgical NEC treatment found that peritoneal drainage followed by laparotomy was associated with decreased mortality compared with peritoneal drainage alone but at significantly increased costs. WHAT'S KNOWN ON THIS SUBJECT:Mortality rates and health care expenditures are high among infants requiring surgery for necrotizing enterocolitis. The impact of different surgical managements on mortality remains equivocal. Adjusted economic differences for various surgical treatments may exist but have not been elucidated. WHAT THIS STUDY ADDS:After performing a relatively large-scale, adjusted analysis of cost and mortality for surgical managements currently used for treating necrotizing enterocolitis, a costbenefit for a particular surgical approach was demonstrated while accounting for comorbidities and group assignment bias.

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Background Neonates with gastrointestinal disorders (GD) are at high risk for parenteral nutrition associated liver disease (PNALD). Soybean-based intravenous lipid emulsions (S-ILE) have been associated with PNALD. This study’s objective was to determine if a lower dose when compared to a higher dose of S-ILE prevents cholestasis without compromising growth. Material and Methods This multi-center randomized controlled pilot study enrolled subjects with GD who were ≤ 5 days of age to a low dose (approximately 1 g/kg/day) (LOW) or control dose of S-ILE (approximately 3 g/kg/day) (CON). The primary outcome was cholestasis (direct bilirubin (DB) > 2 mg/dL) after the first seven days of age. Secondary outcomes included growth, PN duration, and late onset sepsis. Results Baseline characteristics were similar between the LOW (n=20) and CON groups (n=16). When the LOW group was compared to the CON group, there was no difference in cholestasis (30% vs. 38%, p=0.7) or secondary outcomes. However, mean (±SE) DB rate of change over the first eight weeks (0.07±0.04 vs. 0.3±0.09 mg/dL/week, p=0.01) and entire study (0.008±0.03 vs. 0.2±0.07 mg/dL/week, p=0.02) was lower in the LOW group when compared to the CON group. Conclusion In neonates with GD who received a lower dose of S-ILE, DB increased at a slower rate in comparison to neonates who received a higher dose of S-ILE. Growth was comparable between the groups. This study demonstrates a need for a larger, randomized controlled trial comparing two different S-ILE doses for cholestasis prevention in neonates at risk for PNALD.

Background Premature infants depend on intravenous fat emulsions to supply essential fatty acids and calories. The dose of soybean-based intravenous fat emulsions (S-IFE) has been associated with parenteral nutrition associated liver disease. This study’s purpose was to determine if low dose S-IFE is a safe and effective preventive strategy for cholestasis in preterm neonates. Materials and Methods This is a multicenter randomized controlled trial in infants with a gestation age (GA) ≤ 29 weeks. Subjects < 48 hours of life were randomized to receive a low (1g/kg/day) or control dose (approximately 3g/kg/day) of S-IFE. The primary outcome was cholestasis, defined as a direct bilirubin ≥ 15% of the total bilirubin at 28 days of life (DOL) or full enteral feeds, whichever was later, after 14 days of parenteral nutrition. Secondary outcomes included growth, length of hospital stay, death, and major neonatal morbidities. Results 136 neonates (67 and 69 in the low and control group, respectively) were enrolled. Baseline characteristic were similar for the two groups. When the low group was compared to the control group, there was no difference in the primary outcome (69% vs. 63%, 95% CI (−0.1, 0.22), p=0.45). While the low group received less S-IFE and total calories over time compared to the control group (p<0.001 and p=0.03, respectively) weight, length and head circumference at 28 DOL, discharge, and over time were not different (p>0.2 for all). Conclusion Compared to the control dose, low dose S-IFE was not associated with a reduction in cholestasis or growth.

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IMPORTANCE There is concern that nonmedical prescription opioid use is associated with an increased risk of later heroin use initiation in adolescents, but to our knowledge, longitudinal data addressing this topic are lacking.OBJECTIVE To determine whether nonmedical prescription opioid use is associated with subsequent initiation of heroin use in adolescents. DESIGN, SETTING, AND PARTICIPANTSThis prospective longitudinal cohort study conducted in 10 high schools in Los Angeles, California, administered 8 semiannual surveys from 9th through 12th grade that assessed nonmedical prescription opioid use, heroin use, and other factors from October 2013 to July 2017. Students were baseline never users of heroin recruited through convenience sampling. Cox regression models tested nonmedical prescription opioid use statuses at survey waves 1 through 7 as a time-varying and time-lagged regressor and subsequent heroin use initiation across waves 2 to 8 as the outcome.EXPOSURES Self-reported nonmedical prescription opioid use (past 30-day [current] use vs past 6-month [prior] use without past 30-day use vs no past 6-month use) at each wave from 1 to 7.MAIN OUTCOMES AND MEASURES Self-reported heroin use initiation (yes/no) during waves 2 to 8. RESULTSOf 3298 participants, 1775 (53.9%) were adolescent girls, 1563 (48.3%) were Hispanic, 548 (17.0%) were Asian, 155 (4.8%) were African American, 529 (16.4%) were non-Hispanic white, and 220 (6.8%) were multiracial. Among baseline never users of heroin in ninth grade with valid data (3298 [97% of cohort enrollees]; mean [SD] age, 14.6 [0.4] years), the number of individuals with outcome data available at each follow-up ranged from 2987 (90.6%) to 3200 (97.0%). The mean per-wave prevalence of prior and current nonmedical prescription opioid use from waves 1 to 7 was 1.9% and 2.7%, respectively. Seventy students (2.1%) initiated heroin use during waves 2 to 8. Prior vs no (hazard ratio, 3.59; 95% CI, 2.14-6.01; P < .001) and current vs no (hazard ratio, 4.37; 95% CI, 2.80-6.81; P < .001) nonmedical prescription opioid use were positively associated with subsequent heroin use initiation. For no, prior, and current nonmedical prescription opioid use statuses at waves 1 to 7, the estimated cumulative probabilities of subsequent heroin use initiation by wave 8 (42-month follow-up) were 1.7%, 10.7%, and 13.1%, respectively. In covariate-adjusted models, associations were attenuated but remained statistically significant and current nonmedical prescription opioid use risk estimates were stronger than corresponding associations of nonopioid substance use with subsequent heroin use initiation.CONCLUSIONS AND RELEVANCE Nonmedical prescription opioid use was prospectively associated with subsequent heroin use initiation during 4 years of adolescence among Los Angeles youth. Further research is needed to understand whether this association is causal.