Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031914-122957

The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

/pdf/pediatric-complex-chronic-conditions-classification-system-43p4kqgtmd.pdf

Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation

Context Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome primarily caused by maternal opiate use. No national estimates are available for the incidence of maternal opiate use at the time of delivery or NAS. Objectives To determine the national incidence of NAS and antepartum maternal opiate use and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. Design, Setting, and Patients A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1000 hospital births. Missing hospital charges ( Main Outcome Measures Incidence of NAS and maternal opiate use, and related hospital charges. Results The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784 191 to 1.1 million discharges for children (KID) and 816 554 to 879 910 discharges for all ages of delivering mothers (NIS). Between 2000 and 2009, the incidence of NAS among newborns increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year (P for trend  Conclusion Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.

/pdf/neonatal-abstinence-syndrome-and-associated-health-care-2crm396mzd.pdf

Neonatal Abstinence Syndrome and Associated Health Care Expenditures

Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012

Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012.

A RECENT NATIONAL STUDY indicated that illicit drug use is 16.2% among pregnant teens and 7.4% among pregnant women aged 18 to 25 years. Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome in newborns following birth. The syndrome most commonly occurs in the context of antepartum opiate use, although other drugs have also been implicated. In addition to NAS, illicit drug use (specifically opioid dependence) during pregnancy is associated with a signi f icant ly increased risk of adverse neonatal outcomes such as low birthweight ( 2500 g) and mortality. Neonatal abstinence syndrome is characterized by a wide array of signs and symptoms including increased irritability, hypertonia, tremors, feeding intolerance, emesis, watery stools, seizures, and respiratory distress. Symptoms of withdrawal associated with NAS have been described in 60% to 80% of newborns exposed to heroin or methadone in utero.

Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000 to 2009

OBJECTIVE: The objective was to describe the characteristics of pediatric discharges associated with long-term mechanical ventilation (LTMV) compared with those with complex chronic conditions (CCCs), and evaluate trends over time in health care utilization for the discharges associated with LTMV. METHODS: The Kids9 Inpatient Database, compiled by the Agency for Healthcare Research and Quality, was used. Routine newborn care was excluded. Discharges associated with LTMV were identified by using the International Classification of Diseases, Ninth Revision, code v46.1x and compared with discharges associated with CCCs in 2006 using simple regression and χ2 analyses. Trends in LTMV-associated discharges from 2000 to 2006 were assessed using variance-weighted least squares regression. RESULTS: In 2006, there were an estimated 7812 discharges associated with LTMV. Compared with discharges for children with CCCs, LTMV discharges had significantly higher mortality, longer lengths of stay, higher mean charges, more emergency department admissions, and more discharges to long-term care. From 2000 to 2006, there was a 55% increase in the number of LTMV discharges and a concurrent 70% increase in aggregate hospital charges. The majority of LTMV discharges occurred in children 4 years old and younger, and ∼50% of the aggregate charges were for children younger than 1 year. CONCLUSIONS: Discharges for children associated with LTMV require substantively greater inpatient resource use than other children with CCCs. As the number of discharges and associated aggregate charges increase over time, additional research must examine patterns of care for specific clinical subgroups of LTMV, especially children aged 4 years and younger.

/pdf/inpatient-health-care-utilization-for-children-dependent-on-4p4bkwnh23.pdf

Inpatient Health Care Utilization for Children Dependent on Long-term Mechanical Ventilation

In 1998, a live, attenuated tetravalent rotavirus vaccine (RotaShield; Wyeth) was recommended for routine use in infants but was then withdrawn in 1999 after concerns arose suggesting an excess risk of intussusception among infants in the weeks following receipt of vaccine.1,2 As a result, larger prelicensure trials with more than 60 000 infants were performed for a pentavalent rotavirus vaccine (RotaTeq; Merck) and a monovalent rotavirus vaccine (Rotarix; GlaxoSmithKline), neither of which was associated with an increased risk of intussusception.3,4 Trial data led to licensure of both vaccines (RotaTeq, 2006; Rotarix, 2008) and the reintroduction of routine rotavirus vaccination for infants in the United States, with 2007 as the first full year of vaccination efforts.

To date, postlicensure surveillance studies in the United States have not detected an increased risk of intussusception among rotavirus vaccine recipients.5,6 In contrast, postlicensure active surveillance studies in 69 hospitals in Mexico and Brazil found a small increased risk of intussusception (1 in 51 000 to 1 in 68 000) for infants receiving the first or second dose of monovalent rotavirus vaccine.7 In addition, a recent study in Australia found an increased risk of intussusception in the weeks following the first dose of rotavirus vaccine but no overall increase in the risk of intussusception for vaccinated children aged 1 to 9 months.8

These concerns about intussusception re-emerge at the same time that rapid national adoption of rotavirus vaccination in the United States9 has been associated with significant reductions in diarrhea-associated outpatient and emergency department (ED) visits10–12 and hospitalizations11–15 during rotavirus seasons. The small but clinically significant increased risk of intussusception now reported from international studies, combined with the widespread adoption of rotavirus vaccine in the United States, raises concern for the possibility of increasing intussusception rates with continuing widespread use of rotavirus vaccine. Given the rare incidence of intussusception, it is plausible that surveillance networks may not have the reach or statistical power to identify significant changes in patterns of this condition.

Therefore, we sought to address the following question using national data: Has there been a change in hospitalizations for intussusception in infants after the reintroduction of rotavirus vaccine in the United States? To answer this question, we analyzed publicly available data from 3 different sources to examine intussusception rates over time and to estimate excess cases of intussusception that would be predicted based on available rotavirus vaccination coverage rates and the increased risk found in the recent international studies.

https://jamanetwork.com/journals/jamapediatrics/articlepdf/1148402/poa110053_350_355.pdf

Hospitalizations for intussusception before and after the reintroduction of rotavirus vaccine in the United States.

OBJECTIVE: Timely, high quality communication with families is essential to family-centered decision-making. Quality communication is represented by widespread documentation of prognostic, goals-of-care conversations (PGOCC) in the pediatric intensive care unit (PICU) and should occur without variation by patient characteristics. METHODS: Cohort included 645 PICU admissions in the top decile of risk of mortality on admission over six years. Electronic medical records were used to determine PGOCC, diagnosis on admission and complex chronic condition (CCC) status. Multivariate logistic regression and time-to-event analyses were used. RESULTS: Overall, 31% had a documented PGOCC. 51% had CCC status. 11% had an oncologic, 13% had a cardiovascular diagnosis on admission. 94% of patients who died in the PICU had PGOCC documented, but among the 200 patients with documented PGOCC, 78% did not die in the PICU. Oncologic diagnosis on admission was associated with a higher likelihood of PGOCC compared to non-CCC patients (ARR=1.86; SE=0.26) whereas no other diagnosis category reached the level of statistical significance. Median time from admission to PGOCC was 2 days. Age, gender and CCC status were not associated with whether a PGOCC was documented or with time from admission to PGOCC documentation. 45% of PGOCC in the cohort and 50% of conversations in patients with CCC were documented by PICU physicians. CONCLUSIONS: This study reveals the opportunity for improvement in documentation of PGOCC for critically ill children. It raises the questions of why there is variation of PGOCC across disease categories and whether PGOCC should be considered a quality measure for family-centered care.

https://pediatrics.aappublications.org/content/pediatrics/131/Supplement_1/S90.full.pdf

The Factors Associated With High-Quality Communication for Critically Ill Children

Tirzepatide, a once weekly GIP/GLP-1 receptor agonist in development for T2D, demonstrated superior glycemic control in the Phase 3 SURPASS clinical trial program. This post-hoc analysis assessed glycemic control with tirzepatide in participants stratified by baseline (BL) HbA1c (≤8.5%, >8.5%) . Mean change from BL in HbA1c was assessed in tirzepatide-treated participants (5, or 15 mg) from SURPASS-1 (monotherapy) , SURPASS-2 (add-on to MET) , SURPASS-3 (add on to MET ± SGLT2i) , SURPASS-4 (add-on to MET, SGLT2i, or sulfonylurea) and SURPASS-5 (add-on to insulin glargine ± MET) at trial endpoints (40 or 52 weeks) . Safety was also presented. Treatment comparisons were estimated using data while participants were on treatment and without rescue medications (efficacy estimand) . Across each SURPASS trial, ranges in mean BL HbA1c were 7.94-8.52%, mean BMI were 31.9-34.2 kg/m2 and mean diabetes duration were 4.7-13.3 years. At trial endpoints, HbA1c reductions from BL ranged from 1.55-2.14% in the BL HbA1c ≤8.5% subgroup and 2.70-3.46% in the BL HbA1c >8.5% subgroup (Table) . Gastrointestinal side effects were similar to those reported in the incretin class and hypoglycemic events (blood glucose <54 mg/dL or severe) were low. In conclusion, significant and clinically meaningful HbA1c reductions were observed with tirzepatide, irrespective of BL HbA1c.
 
 
 
 G.Aleppo: Consultant; Insulet Corporation, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Fractyl Health, Inc., Insulet Corporation, Novo Nordisk, Speaker's Bureau; Dexcom, Inc. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. J.A.Levine: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.Gomez-valderas: Employee; Lilly, Stock/Shareholder; Lilly. B.D.Benneyworth: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.
 
 
 
 Eli Lilly and Company


Brian D. Benneyworth

Papers

Neonatal Abstinence Syndrome and Associated Health Care Expenditures

Inpatient Health Care Utilization for Children Dependent on Long-term Mechanical Ventilation

Hospitalizations for intussusception before and after the reintroduction of rotavirus vaccine in the United States.

The Factors Associated With High-Quality Communication for Critically Ill Children

717-P: Glycemic Control with Tirzepatide in People with Type 2 Diabetes by Baseline HbA1c =8.5% or >8.5%