Kristin A. Shadman

A review of palivizumab and emerging therapies for respiratory syncytial virus.

Introduction: Respiratory syncytial virus (RSV) is an important pathogen in children and adults; however, current treatment options are primarily supportive. Palivizumab, the only approved specific monoclonal antibody for RSV is used prophylactically to reduce morbidity in a select population of high-risk children. Areas covered: The development and current use of palivizumab; the potential role of palivizumab as preventive therapy in patients with cystic fibrosis, asthma and compromised immune systems; and explores the limited research in which palivizumab has been used for treatment of RSV. The modified recommendations for the use of palivizumab espoused by the American Academy of Pediatrics and research on the cost-effectiveness of this product are presented. In addition, the authors discuss the development of enhanced monoclonal antibodies including motavizumab, which was recently denied FDA approval for preventative therapy. The authors explore the historical and current efforts to develop a vaccine targeting RSV. The current status of antiviral drug development is also reviewed. The literature search included RSV-Ig, palivizumab, and emerging drugs and vaccines for the treatment of RSV as keywords and titles from 1997 to 2011. Expert opinion: Although there are potential drugs and vaccines in development to prevent or reduce the effects of RSV infection, palivizumab remains the only licensed product to reduce the severity of disease in high-risk pediatric patients.

Treatment Trends and Outcomes in US Hospital Stays of Children With Empyema

Background: Recently published practice guidelines continue to reflect uncertainty about the comparative effectiveness of various treatments for empyema in children. We describe treatment trends and outcomes in pediatric empyema using the most current nationally representative data. Methods: Using survey methods and Kids’ Inpatient Databases from 1997 to 2009, we evaluated hospital stays in children 0–18 years of age. We used 2009 data to compare transfer-out rates and lengths of stay across various types of treatment, after adjusting for patient and hospital factors. Results: From 1997 to 2009, empyema discharges steadily increased from 3.1 to 6.0 per 100,000 children (P < 0.001 for trend) and also were increasingly likely (P < 0.01) to be coded for: (1) at least 1 pleural drainage procedure (76.4–83.2%), (2) multiple drainage procedures (36.0–41.6%) and (3) home health care (8.7–15.0%). By 2009, video-assisted thoracoscopic surgery was more commonly coded than chest tube drainage and was associated with a lower transfer-out rate (0.6% vs. 10.1%, adjusted P < 0.001) but no reduction in mean length of stay [11.2 vs. 13.4 days, adjusted incidence rate ratio 0.95 (95% confidence interval: 0.88–1.04)] for children neither admitted nor discharged by transfer. Conclusions: US hospital stays for empyema in children not only continued to increase through 2009 but were also characterized by more intense procedural management. Outcomes results in this population-based study are consistent with practice guidelines and recommendations that recently endorsed chest tube drainage as an acceptable first treatment option for most children with empyema.

Improving safe sleep practices for hospitalized infants

BACKGROUND AND OBJECTIVES: Adherence to the American Academy of Pediatrics safe sleep practice (SSP) recommendations among hospitalized infants is unknown, but is assumed to be low. This quality improvement study aimed to increase adherence to SSPs for infants admitted to a children’s hospital general care unit between October 2013 and December 2014. METHODS: After development of a hospital policy and redesign of room setup processes, a multidisciplinary team developed intervention strategies based on root cause analysis and implemented changes using iterative Plan–Do–Study–Act cycles. Nurse knowledge was assessed before and after education. SSPs were measured continuously with room audits during sleeping episodes. Statistical process control and run charts identified improvements and sustainability in hospital SSPs. Caregiver home practices after discharge were assessed via structured questionnaires before and after intervention. RESULTS: Nursing knowledge of SSPs increased significantly for each item (P ≤ .001) except avoidance of bed sharing. Audits were completed for 316 sleep episodes. Simultaneous adherence to all SSP recommendations improved significantly from 0% to 26.9% after intervention. Significant improvements were noted in individual practices, including maintaining a flat, empty crib, with an appropriately bundled infant. The largest gains were noted in the proportion of empty cribs (from 3.4% to 60.3% after intervention, P < .001). Improvements in caregiver home practices after discharge were not statistically significant. CONCLUSIONS: Sustained improvements in hospital SSPs were achieved through this quality improvement initiative, with opportunity for continued improvement. Nurse knowledge increased during the intervention. It is uncertain whether these findings translate to changes in caregiver home practices after discharge.

Transitioning from General Pediatric to Adult-Oriented Inpatient Care: National Survey of US Children’s Hospitals

BACKGROUND: Hospital charges and lengths of stay may be greater when adults with chronic conditions are admitted to childrens hospitals. Despite multiple efforts to improve pediatric‐adult healthcare transitions, little guidance exists for transitioning inpatient care. OBJECTIVE: This study sought to characterize pediatricadult inpatient care transitions across general pediatric services at US childrens hospitals. DESIGN, SETTING, AND PARTICIPANTS: National survey of inpatient general pediatric service leaders at US childrens hospitals from January 2016 to July 2016. MEASUREMENTS: Questionnaires assessed institutional characteristics, presence of inpatient transition initiatives (having specific process and/or leader), and 22 inpatient transition activities. Scales of highly correlated activities were created using exploratory factor analysis. Logistic regression identified associations between institutional characteristics, transition activities, and presence of an inpatient transition initiative. RESULTS: Ninety‐six of 195 childrens hospitals responded (49.2% response rate). Transition initiatives were present at 38% of childrens hospitals, more often when there were dual‐trained internal medicine‐pediatrics providers or outpatient transition processes. Specific activities were infrequent and varied widely from 2.1% (systems to track youth in transition) to 40.5% (addressing potential insurance problems). Institutions with initiatives more often consistently performed the majority of activities, including using checklists and creating patient‐centered transition care plans. Of remaining activities, half involved transition planning, the essential step between readiness and transfer. CONCLUSIONS: Relatively few inpatient general pediatric services at US childrens hospitals have leaders or dedicated processes to shepherd transitions to adultoriented inpatient care. Across institutions, there is a wide variability in performance of activities to facilitate this transition. Feasible process and outcome measures are needed. Journal of Hospital Medicine 2018;13:13‐20.

Respiratory Scores as a Tool to Reduce Bronchodilator Use in Children Hospitalized With Acute Viral Bronchiolitis

BACKGROUND AND OBJECTIVES Adoption of clinical respiratory scoring as a quality improvement (QI) tool in bronchiolitis has been temporally associated with decreased bronchodilator usage. We sought to determine whether documented use of a clinical respiratory score at the patient level was associated with a decrease in either the physician prescription of any dose of bronchodilator or the number of doses, if prescribed, in a multisite QI collaborative. METHODS We performed a secondary analysis of data from a QI collaborative involving 22 hospitals. The project enrolled patients aged 1 month to 2 years with a primary diagnosis of acute viral bronchiolitis and excluded those with prematurity, other significant comorbid diseases, and those needing intensive care. We assessed for an association between documentation of any respiratory score use during an episode of care, as well as the method in which scores were used, and physician prescribing of any bronchodilator and number of doses. Covariates considered were phase of the collaborative, hospital length of stay, steroid use, and presence of household smokers. RESULTS A total of 1876 subjects were included. There was no association between documentation of a respiratory score and the likelihood of physician prescribing of any bronchodilator. Score use was associated with fewer doses of bronchodilators if one was prescribed (P = .05), but this association disappeared with multivariable analysis (P = .73). CONCLUSIONS We found no clear association between clinical respiratory score use and physician prescribing of bronchodilators in a multicenter QI collaborative.

Trends in Hospital Treatment of Empyema in Children in the United States

Objective To evaluate trends in procedures used to treat children hospitalized in the US with empyema during a period that included the release of guidelines endorsing chest tube placement as an acceptable first‐line alternative to video‐assisted thoracoscopic surgery. Study design We used National Inpatient Samples to describe empyema‐related discharges of children ages 0‐17 years during 2008‐2014. We evaluated trends using inverse variance weighted linear regression and characterized treatment failure using multivariable logistic regression to identify factors associated with having more than 1 procedure. Results Empyema‐related discharges declined from 3 in 100 000 children to 2 in 100 000 during 2008‐2014 (P = .04, linear trend). There was no significant change in the proportion of discharges having 1 procedure (66.1% to 64.1%) or in the proportion having 2 or more procedures (22.1% to 21.6%). The proportion coded for video‐assisted thoracoscopic surgery as the only procedure declined (41.4% to 36.2%; P = .03), and the proportions coded for 1 chest tube (14.6% to 20.9%; P = .04) and 2 chest tube procedures (0.9% to 3.5%; P < .01) both increased. The median length of stay for empyema‐related discharges remained unchanged (9.3 days to 9.8 days; P = .053). Having more than 1 procedure was associated with continuous mechanical ventilation (adjusted OR, 2.7; 95% CI, 1.8‐4.1) but not with age, sex, payer, chronic conditions, transfer admission, hospital size, or census region. Conclusions The use of video‐assisted thoracoscopic surgery to treat children in the US hospitalized with empyema seems to be decreasing without associated increases in length of stay or need for additional drainage procedures.

Implementing Parental Tobacco Dependence Treatment Within Bronchiolitis QI Collaboratives

Systematic tobacco dependence interventions directed at parents and/or caregivers were implemented as secondary aims in multicenter QI collaboratives targeted at improving care for children with bronchiolitis. BACKGROUND AND OBJECTIVES: We sought to implement systematic tobacco dependence interventions for parents and/or caregivers as secondary aims within 2 multisite quality improvement (QI) collaboratives for bronchiolitis. We hypothesized that iterative improvements in tobacco dependence intervention strategies would result in improvement in outcomes between collaboratives. METHODS: This study involved 2 separate yearlong, multisite QI collaboratives that were focused on care provided to inpatients with a primary diagnosis of bronchiolitis. In each collaborative, we provided tools and training in tobacco dependence treatment and expert coaching on interventions for parents as a secondary aim. Data were collected by chart review and results analyzed by using analysis of means and statistical process control analysis. Outcomes between collaboratives were compared by using relative risks. RESULTS: Between both collaboratives, 56 hospitals participated and 6258 inpatient charts were reviewed. In the first collaborative, 22% of identified parents who smoke received tobacco dependence interventions at baseline. This rate increased to 51% during the postintervention period, with special cause revealed by analysis of means. In the second collaborative, 31% of parents who smoke received baseline interventions. This rate increased to 53% by the conclusion of the collaborative, with special cause revealed by statistical process control analysis. The relative risk for providing any cessation intervention in 1 collaborative versus the other was 0.9 (confidence interval 0.8–1.1). CONCLUSIONS: Tobacco dependence treatment of parents and/or caregivers can be integrated into bronchiolitis QI by using relatively low-resource strategies. Using a more intensive QI intervention did not alter the rates of screening or intervention for caregivers who smoke.

Response to: palivizumab and emerging therapies for respiratory syncytial virus

Thank you for the opportunity to respond to the letter regarding our manuscript in Expert Opinion on Biological Therapy [1]. We greatly appreciate interest in the article. The article addresses the current clinical and research usage of palivizumab in patients with cystic fibrosis, immunocompromised states, and those at high risk of developing asthma. We do not imply that palivizumab has received FDA approval for such indications. Section 2.3 states that “licensure of motivizumab has not been granted” [1]. Regarding the IMpact trial, our text states that it “showed a 55% reduction in hospitalization” for BPD and includes the eligibility criteria of “premature less than 35 weeks and less than 6 months of age” which are both stated in the original article [2]. Our article concurs with the respondents who state that the premature children born 35 weeks GA or less and £ 6 months were eligible for the study [1]. We concur that the liquid formulation of palivizumab is injectable, as well as that study NCT00435227 has been completed. Finally, the expert opinion section states that palivizumab has been demonstrated to be safe and well tolerated [1]. We would not dispute that safety has been demonstrated in premature infants born less than 35 weeks gestational age who are less than 6 months prior to the start of RSV season as this was established in the IMpact trial [2]. The cost benefit analysis of treating infants between 32 weeks and 34 week 6 days with palivizumab has been less clearly demonstrated, which is presented in Section 2.2.1 [1].