Trends in Pediatric Primary Immunodeficiency: Incidence, Utilization, Transplantation, and Mortality.

BACKGROUND: Primary immunodeficiency disorders (PIDDs) describe a myriad of diseases caused by inherited defects within the immune system. As the number of identified genetic defects associated with PIDDs increases, understanding the incidence and outcomes of PIDD patients becomes imperative. OBJECTIVE: To characterize the frequency of new diagnoses, patterns of health care utilization, rates of hematopoietic stem cell transplantation (HSCT), and mortality in pediatric patients with PIDDs. METHODS: A retrospective cohort analysis of the Pediatric Health Information System database from 2004 to 2018 for pediatric inpatients with an International Classification of Diseases, Ninth and 10th Revisions (ICD-9/ICD-10). code associated with PIDD. RESULTS: A total of 17,234 patients with a PIDD were hospitalized from 2004 to 2018. There were 2.8 new PIDD diagnoses and 6.3 PIDD hospitalizations per 1,000 discharges; these metrics were unchanged during the study period. The number of new diagnoses for B-cell and antibody defects significantly increased over time. The number of new PIDD diagnoses significantly increased in adolescents or adults and decreased in infants. T-cell disorders had the highest number of intensive care unit admissions. There were 747 PIDD patients who underwent HSCT; complications of HSCT significantly decreased over time. Mortality rates significantly decreased in all PIDD patients and in patients receiving HSCT. CONCLUSIONS: The total hospitalizations and incidence of PIDDs within the hospitalized pediatric population were unchanged. There were significant changes in the class of PIDD diagnosed, the age at diagnosis, and health care utilization metrics. Mortality significantly decreased over time within the PIDD cohort.

Thrombotic Microangiopathy: Multi-Institutional Review of Pediatric Patients Who Underwent HSCT.

Thrombotic microangiopathy (TMA) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT). The purpose of our study is to estimate the incidence, prevalence, and analyze the risk factors and outcome of TMA in children receiving HSCT. Patients under the age of 21 who underwent HSCT at one of the 42 Pediatric Health Information System (PHIS) hospitals from 2000-2012 were analyzed, including demographics, hospitalizations, TMA, and other HSCT-related complications. From 2000 to 2012, a total of 12,369 unique pediatric patients who received HSCT were identified. Among these, 93 (0.8%) children were identified to have the diagnosis of TMA. TMA was significantly associated with allogeneic HSCT, peripheral blood stem cell trasnplants (PBSCT), cytomegalovirus (CMV), human herpes virus 6 (HHV6), fungal infection, graft-versus-host disease (GVHD), and veno-occlusive disease (VOD) (p = 0.01). Multivariate logistic regression analysis of mortality showed only HHV6 was an independent risk factor associated with increased mortality in patients with TMA (hazard ratio: 2.86 [1.01, 8.39], p = 0.05). The prevalence of TMA in our study is 0.8% with a mortality in our pediatric TMA cohort of 30%, which is in contrast to the higher mortality reported in previously published, small-case series. HHV6 emerged as not only a risk factor for TMA but also as associated with increased mortality in these patients.

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.

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.

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.