Risk Factors for Readmission Following Febrile Neutropenia in Pediatric Oncology Patients.

Febrile neutropenia is the most common reason for admission from the emergency department for pediatric oncology patients. We identified pediatric inpatients age 1 to 21 years with an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code of malignancy and either fever with neutropenia or fever alone over a 6-year period (2007-2012) using the PHIS+ database. We evaluated factors associated with readmission within 7 days after index hospitalization. There were 4029 index hospitalizations among 2349 patients in 6 hospitals, 294 encounters (7.3%) were followed by readmission within 7 days. Factors associated with increased odds of readmission included being in the lowest quartile for median household income (odds ratio [OR]=1.64, P =0.009), diagnosis of acute lymphoblastic leukemia (OR=1.37, P =0.016), lack of anerobic coverage during index hospitalization (OR=1.48, P =0.026), and absolute neutrophil count <200 cells/µL at discharge from index hospitalizations (OR=1.55, P =0.008). Patients who required readmission had a longer median length of stay and greater hospitalization costs during the index hospitalization. There was a trend towards increasing hospitalization rates for febrile neutropenia over time. While absolute neutrophil count is incorporated into many risk stratification strategies for fever management, further work should focus on addressing socioeconomic factors which may impact readmission rates.

Premedication prior to PEG-asparaginase is cost-effective in pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions. PROCEDURES: This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. RESULTS: In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes to Erwinia compared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. CONCLUSION: Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

Rhode Island's Opioid Overdose Hospital Standards and Emergency Department Naloxone Distribution, Behavioral Counseling, and Referral to Treatment.

STUDY OBJECTIVE: We sought to determine the influence of the Levels of Care for Rhode Island Emergency Departments and Hospitals for Treating Overdose and Opioid Use Disorder (Levels of Care) on emergency department (ED) provision of take-home naloxone, behavioral counseling, and referral to treatment. METHODS: A retrospective analysis of Rhode Island ED visits for opioid overdose from 2017 to 2018 was performed using data from a statewide opioid overdose surveillance system. Changes in provision of take-home naloxone, behavioral counseling, and referral to treatment before and after Levels of Care implementation were assessed using interrupted time series analysis. We compared outcomes by hospital type using multivariable modified Poisson regression models with generalized estimating equation estimation to account for hospital-level variation. RESULTS: We analyzed 245 overdose visits prior to Levels of Care implementation (January to March 2017) and 1340 overdose visits after implementation (hospital certification to December 2018). After implementation, the proportion of patients offered naloxone increased on average by 13% (95% confidence interval [CI] 5.6% to 20.4%). Prior to implementation, the proportion of patients receiving behavioral counseling and treatment referral was declining. After implementation, this decline slowed and stabilized, and on average 18.6% more patients received behavioral counseling (95% CI 1.3% to 35.9%) and 23.1% more patients received referral to treatment (95% CI 2.7% to 43.5%). Multivariable analysis showed that after implementation, there was a significant increase in the likelihood of being offered naloxone at Level 1 (adjusted relative risk [aRR] 1.31 [95% CI 1.06 to 1.61]) and Level 3 (aRR 3.13 [95% CI 1.08 to 9.06]) hospitals and an increase in referrals for medication for opioid use disorder (from 2.5% to 17.8%) at Level 1 hospitals (RR 7.73 [95% CI 3.22 to 18.55]). Despite these increases, less than half of the patients treated for an opioid overdose received behavioral counseling or referral to treatment CONCLUSION: The establishment of ED policies for treatment and services after opioid overdose improved naloxone distribution, behavioral counseling, and referral to treatment at hospitals without previously established opioid overdose services. Future investigations are needed to better characterize implementation barriers and evaluate policy influence on patient outcomes.

Is Skill Type the Key to the PreK Fadeout Puzzle? Differential Associations Between Enrollment in PreK and Constrained and Unconstrained Skills Across Kindergarten.

This study examines whether associations between enrollment in public and non-public PreK and children's (N = 508; Mage  = 5.60 years in fall of kindergarten) math and language and literacy outcomes were more likely to be sustained through the spring of kindergarten for unconstrained versus constrained skills. Associations between public PreK and language, literacy, and math outcomes were more strongly sustained through the spring of kindergarten for unconstrained skills, relative to constrained skills. Only associations between non-public PreK and unconstrained language skills were sustained through the spring of kindergarten. Associations in the fall of kindergarten differed by family income and dual language learner (DLL) status but there was no subgroup variation by the spring of kindergarten. Implications for policy and practice are discussed.

Impact of PCV-13 vaccine on invasive pneumococcal disease in hospitalised children: A multi-institutional analysis.

AIM: We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately. The primary outcome was IPD incidence. Secondary outcomes included length of stay, intensive care unit (ICU) admission, mechanical ventilation and mortality. RESULTS: 9160 hospitalisations for IPD were included. The IPD rate per 100 000 discharges was 180 pre-PVC13 and 150 post-PCV13 [17% decrease (P = 0.085)]. The observed IPD rate in 2017 was 45.5% lower than the rate predicted by the pre-PCV13 trend (95% CI: 44%-46%). While a significant decrease in IPD (32%, P = 0.026) was observed among healthy children, there was no change in those with chronic conditions (9%, P = 0.24). In the post-PCV13 period, more IPD patients had chronic conditions, ICU admissions and longer ICU stays. CONCLUSION: Although there was no overall reduction in IPD after PCV13, we observed a significant decrease in IPD among healthy patients. Further research is needed to elucidate microbiology or other factors contributing to persistent IPD hospitalisations.

The mediating role of child-teacher dependency in the association between early mother-child attachment and behavior problems in middle childhood.

This study examines child-teacher dependency in preschool as a pathway through which mother-child attachment is associated with children's behavior problems across middle childhood. Data include direct assessments of attachment security and styles, teacher reports of child-teacher dependency, and maternal reports of behavior problems from the NICHD SECCYD (N = 769 children). Children with more secure attachments at 24 months were less likely to exhibit child-teacher dependency at 54 months. Children with ambivalent, controlling, or insecure/other attachments at 36 months had higher levels of child-teacher dependency at 54 months. Results from multi-level models showed that child-teacher dependency at 54 months was associated with higher levels of internalizing, but not externalizing, behavior problems across middle childhood. Child-teacher dependency partially mediated the association between insecure/other mother-child attachment and internalizing behaviors in middle childhood. Supporting preschool teachers to reduce child-teacher dependency may help ameliorate risk for internalizing behaviors posed by insecure/other attachment.

Acute kidney injury in paediatric patients with sickle cell disease is associated with increased morbidity and resource utilization.

Renal disease is a common complication experienced by patients with sickle cell disease (SCD), though the epidemiology of acute kidney injury (AKI) in paediatric patients and its impact on long-term renal outcomes is unclear. We utilized the Pediatric Health Information System (PHIS) to identify inpatient encounters of paediatric patients with SCD admitted for vaso-occlusive pain crisis (VOC). Overall, 1·4% of patients experienced at least one episode of AKI and 2·5% of admissions were complicated by AKI. Patients with at least one episode of AKI were more likely to be adolescents or young adults at the time of their initial admission, had increased rates of admission to the ICU, longer lengths of stay, increased costs of hospitalization, increased risk of readmission and increased rates of SCD-related comorbidities. Generalized estimating equation modelling demonstrated that increasing age, history of hypertension, history of haematuria and history of chronic kidney disease were associated with increased odds of developing AKI, though hydroxycarbamide use (OR 0·64, 95% CI 0·44-0·94) was protective. Episodes of AKI during hospitalization in children with SCD are associated with increased morbidity and utilization of hospital resources. Increasing the use of hydroxycarbamide may decrease the likelihood of this complication.

Cost-effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia.

BACKGROUND: Infections are the leading cause of therapy-related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost-effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost-effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML. PROCEDURE: A retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one-way sensitivity analyses evaluated model uncertainty. RESULTS: Prophylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness-to-pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost-effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive. CONCLUSION: Prophylaxis is cost-effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.

Hyperglycemia requiring insulin during acute lymphoblastic leukemia induction chemotherapy is associated with increased adverse outcomes and healthcare costs.

BACKGROUND: Hyperglycemia is a complication of induction chemotherapy in 10%-50% of pediatric patients with acute lymphoblastic leukemia (ALL). Though hyperglycemia in ALL patients is usually transient, it may be associated with adverse health outcomes. However, the risk factors for and consequences of hyperglycemia are poorly understood. We hypothesized that hyperglycemia significant enough to require insulin therapy during induction chemotherapy would be associated with increased morbidity and mortality in pediatric ALL patients during induction chemotherapy and in subsequent care. METHODS: We abstracted clinical and resource utilization data from the Pediatric Health Information System (PHIS) database utilizing ICD-9 codes and medication charges. We used logistic regression analysis to predict the development of hyperglycemia. The effects of hyperglycemia on binary and count adverse outcomes following induction chemotherapy were modeled using mixed-effect regression models. RESULTS: An increased risk of hyperglycemia requiring insulin was associated with older age, female sex, higher risk group and trisomy 21. Patients on insulin for hyperglycemia had increased mortality following induction chemotherapy. These patients were more likely to have subsequent infectious complications, need for bone marrow transplant, and risk of disease relapse. They also had greater length of inpatient stay, higher cost of care, and were more likely to require intensive care unit admission during induction chemotherapy. CONCLUSIONS: Hyperglycemia requiring insulin during induction chemotherapy in pediatric ALL is associated with an increased risk of short-term and long-term complications. Prospective studies are needed to analyze formal screening, preventive measures, and optimal management practices for hyperglycemia during ALL induction chemotherapy.

Multidisciplinary Team Reviews of Drug Overdose Deaths and the Use of Minigrants to Advance Recommendations: A Statewide Pilot in Rhode Island.

CONTEXT: Rhode Island has been significantly impacted by the opioid epidemic, ranking 11th in unintentional drug overdose rates in the United States in 2017. Illicit fentanyl was involved in the majority of these deaths. PROGRAM: To enhance surveillance of this epidemic, the RI Department of Health piloted in-depth, multidisciplinary, and multiagency team reviews of drug overdose deaths. The goals were to identify gaps in policies and programming and develop recommendations to prevent future deaths. Time-sensitive minigrants were offered to nonprofit organizations as a novel way to further the recommendations put forth from these reviews. IMPLEMENTATION: Legal agreements between select state agencies and institutions enabled broad team representation and the sharing of information during each meeting. Reviews, revolving around a common theme, were conducted for up to 10 deaths each quarter. Recommendations for prevention were generated by the team and summarized in a report to the Governor's Overdose Prevention and Intervention Task Force and the public within 1 month of each meeting. Announcements of minigrant opportunities and funding to advance the community-specific recommendations were paired with each meeting. EVALUATION: From November 2016 through May 2018, the pilot team convened 7 times, generated 78 recommendations, and distributed 31 minigrants. Early process evaluations of these grants have shown positive impact within local environments. Following the pilot phase, state legislation for these reviews was passed in June 2018. DISCUSSION: The RI Department of Health was able to successfully pilot a multidisciplinary review process for overdose deaths and has recently institutionalized this process through legislation. The successful implementation of many of the team's community-oriented recommendations, supported through a minigrant process, highlights the impact that small financial investments can have to address the opioid epidemic and may be a model for other jurisdictions seeking to advance recommendations from these types of reviews.

Emergency Department and Hospital Care for Opioid Use Disorder: Implementation of Statewide Standards in Rhode Island, 2017-2018.

In March 2017, Rhode Island released treatment standards for care of adult patients with opioid use disorder. These standards prescribe three levels of hospital and emergency department treatment and prevention of opioid use disorder and opioid overdose and mechanisms for referral to treatment and epidemiological surveillance. By June 2018, all Rhode Island licensed acute care facilities had implemented policies meeting the standards' requirements. This policy has standardized care for opioid use disorder, enhanced opioid overdose surveillance and response, and expanded linkage to peer recovery support, naloxone, and medication for opioid use disorder.

Marital Interactions, Family Intervention, and Disagreements: A Daily Diary Study in a Low-income Sample.

Little research has examined associations between low-income married couples' daily interactions and severity of disagreements. Similarly, few researchers have considered how family-strengthening interventions for low-income couples may affect the quality of daily interactions and associations between interactions and conflict experiences. This study aims to fill these gaps in the literature by leveraging daily diary data from a random assignment study of a family-strengthening intervention with low-income husbands and wives 30 months postenrollment. Married couples randomly assigned to the intervention participated in 10 weeks of relationship education services. Control group couples received no services. Thirty months postrandom assignment, participants reported on the severity of daily marital disagreements over a 15-day period, as well as their positive and negative emotions during inter-spousal interactions. Multi-level models demonstrated associations between reports of emotions in interactions and severity of disagreements. In addition, wives assigned to the family strengthening program reported fewer negative emotions during interactions at follow-up than wives in the control condition. Finally, negative associations between positive emotions in interactions and severity of disagreements were stronger for wives assigned to the intervention, while positive associations between negative emotions in interactions and severity of disagreements were weaker for wives assigned to the intervention. Implications for future research and intervention development are discussed.

Can Emergency Department, Hospital Discharge, and Death Data Be Used to Monitor Burden of Drug Overdose in Rhode Island?

CONTEXT: Drug overdoses are a growing public health problem in the United States. Rhode Island is also confronted with a serious epidemic of drug overdose deaths and ranks sixth worst in the United States for age-adjusted drug overdose death rate. OBJECTIVE: To monitor trends of drug overdose-related emergency department (ED) visits, hospitalizations, and deaths and classify the drug overdoses by demographics, discharge status, intent, and specific drug involved to plan for health care resource allocation, mental health services, drug abuse treatment, prevention, and policies. DESIGN: Cross-sectional study. SETTING: The 2005-2014 ED, hospital discharge, and death data were used for this study. MAIN OUTCOME MEASURE: Age-adjusted rates were calculated by using age-specific Rhode Island 2010 standard population. Healthcare Cost and Utilization Project cost-to-charge ratios were used to convert total hospital charges to costs. The descriptive analysis was performed. RESULTS: Hospitalizations generally represent the most severe cases; there are substantially fewer cases than are seen in the ED, and their characteristics are different from ED visits. More than half of the ED cases were an unintentional injury by drug overdose, but more than half of the hospital discharge data cases were a suicide/self-inflicted injury by drug overdose. There were typically much more females than males that result in a hospital admission. In Rhode Island, there were 249 drug overdose deaths in 2014. Drug overdose fatalities were more likely to be young, male, white, and those who reside in suburban regions. IMPLICATIONS: Nonfatal and fatal drug overdose data are important for understanding the scope, incidence, and breadth of this public health epidemic and can guide overdose intervention efforts. In Rhode Island, policy makers can use drug overdose data to target high-risk subpopulations to reduce overdose injuries and fatalities. The Rhode Island study can be shared with other states. CONCLUSIONS: Regardless of the type of drug, overdoses remain a public health crisis in Rhode Island. It is a dynamic epidemic and needs partnership among public health, behavioral health, public safety, clinic, pharmacy, and communities. The ability to track drug overdose in real time will be an essential tool to respond to the constantly evolving drug overdose epidemic in Rhode Island quickly and effectively.

Context Matters for Social-Emotional Learning: Examining Variation in Program Impact by Dimensions of School Climate.

This paper examines whether three dimensions of school climate-leadership, accountability, and safety/respect-moderated the impacts of the INSIGHTS program on students' social-emotional, behavioral, and academic outcomes. Twenty-two urban schools and N = 435 low-income racial/ethnic minority students were enrolled in the study and received intervention services across the course of 2 years, in both kindergarten and first grade. Intervention effects on math and reading achievement were larger for students enrolled in schools with lower overall levels of leadership, accountability, and safety/respect at baseline. Program impacts on disruptive behaviors were greater in schools with lower levels of accountability at baseline; impacts on sustained attention were greater in schools with lower levels of safety/respect at baseline. Implications for Social-Emotional Learning program implementation, replication, and scale-up are discussed.

Understanding intrinsically irreversible, non-Nernstian, two-electron redox processes: a combined experimental and computational study of the electrochemical activation of platinum(IV) antitumor prodrugs.

Six-coordinate Pt(IV)-complexes are prominent prodrug candidates for the treatment of various cancers where, upon two-electron reduction and loss of two axial ligands, they form more familiar, pharmacologically active four-coordinate Pt(II) drugs. A series of electrochemical experiments coupled with extensive density functional calculations has been employed to elucidate the mechanism for the two-electron reduction of Pt(IV)(NH3)2Cl2L2 to Pt(II)(NH3)2Cl2 (L = CH3COO(-), 1; L = CHCl2COO(-), 2; L = Cl(-), 3). A reliable estimate for the normal reduction potential E(o) is derived for the electrochemically irreversible Pt(IV) reduction and is compared directly to the quantum chemically calculated reduction potentials. The process of electron transfer and Pt-L bond cleavage is found to occur in a stepwise fashion, suggesting that a metastable six-coordinate Pt(III) intermediate is formed upon addition of a single electron, and the loss of both axial ligands is associated with the second electron transfer. The quantum chemically calculated reduction potentials are in excellent agreement with experimentally determined values that are notably more positive than peak potentials reported previously for 1-3.

Early mother-child attachment and behavior problems in middle childhood: the role of the subsequent caregiving environment.

The current study investigated associations between early mother-child attachment, as well as mother-child and teacher-child relationships, and internalizing and externalizing behaviors in middle childhood. Data from the NICHD Study of Early Child Care and Youth Development were used. Findings from a series of individual growth curve analyses revealed that attachment security was negatively related to internalizing and externalizing behaviors, while insecure/other and avoidant attachment were positively related to internalizing behaviors. In addition, longitudinal associations were found between mother-child and teacher-child relationships and internalizing and externalizing behaviors across middle childhood. Implications for attachment theory are discussed.

One Score to Rule Them All? Comparing the Predictive and Concurrent Validity of 30 Hearts and Flowers Scoring Approaches.

The Hearts and Flowers (H&F) task is a computerized executive functioning (EF) assessment that has been used to measure EF from early childhood to adulthood. It provides data on accuracy and reaction time (RT) across three different task blocks (hearts, flowers, and mixed). However, there is a lack of consensus in the field on how to score the task that makes it difficult to interpret findings across studies. The current study, which includes a demographically diverse population of kindergarteners from Boston Public Schools (N = 946), compares the predictive and concurrent validity of 30 ways of scoring H&F, each with a different combination of accuracy, RT, and task block(s). Our exploratory results provide evidence supporting the use of a two-vector average score based on Zelazo et al.'s approach of adding accuracy and RT scores together only after individuals pass a certain accuracy threshold. Findings have implications for scoring future tablet-based developmental assessments.