SENTINEL1: Two-Season Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

OBJECTIVE: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons. STUDY DESIGN: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized. RESULTS: Results were similar across the two seasons. Among infants with community-acquired RSVH (N = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge. CONCLUSION: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV.

Cost savings associated with timely treatment of botulism with botulism antitoxin heptavalent product.

BACKGROUND: Botulism is a rare, serious, and sometimes fatal paralytic illness caused by exposure to neurotoxins produced by Clostridium botulinum bacteria. Patients with documented or suspected exposure to botulinum toxin serotypes A-G can be treated with BAT® [Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)] product, which was approved in 2013 in the United States (US). Patients with botulism have demonstrated greater clinical benefit with early BAT product treatment (≤2 days from symptom onset) versus late treatment (>2 days). OBJECTIVE: Economic outcomes associated with improved clinical outcome benefits of BAT product treatment have not yet been reported. This ad hoc analysis aimed to estimate and compare costs associated with hospitalization, intensive care unit stay, and mechanical ventilation for patients with botulism administered BAT product treatment early or late. METHODS: Clinical outcomes data for early and late BAT product treatment were obtained from a patient registry conducted between October 2014 and July 2017. Total per patient mean daily costs were estimated based on information from published literature. Total population costs per group were calculated by multiplying estimated mean cost per patient by the average annual number of non-infant botulism cases in the US. RESULTS: Mean per patient costs were 2.5 times lower for patients treated with BAT product early versus late. On average in the US, early BAT product treatment could save greater than $3.9 million per year versus late treatment. CONCLUSION: Substantial economic savings can be achieved with early BAT product treatment. The findings support the recommendation for public health authorities to ensure antitoxin treatment is readily available in sufficient quantities to manage botulism cases, including sporadic outbreaks and potential mass exposure biological attacks.

Impact of Respiratory Syncytial Virus-Confirmed Hospitalizations on Caregivers of US Preterm Infants.

This study assessed the impact of respiratory syncytial virus-confirmed hospitalizations (RSVH) on caregivers of high-risk preterm infants. Caregivers for infants born at 29 to 35 weeks' gestational age and hospitalized for confirmed RSV disease responded to measures of self-rated and perceived infant stress (1-7; 7 = very stressful), perceived infant health (0-100; 100 = best imaginable health), and productivity impairment. Data were collected at hospital discharge through 1 month post-discharge. Caregiver responses indicated high stress levels, poor health, and productivity loss were reported at discharge; however, steady improvements were seen through 1 month post-discharge: caregiver-rated stress (from 6 to 2), infant stress (5 to 1), caregiver-perceived infant health (64 to 84), and productivity loss (mothers: 91% to 31%; fathers: 81% to 18%). Qualitative results indicated emotional impact, family routine disruption, financial concerns, and medical concerns persisted at 1 month post-discharge. This study found the caregiver burden of RSVH persists at least 1 month beyond discharge.

SENTINEL1: An Observational Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

Objective SENTINEL1 characterized U.S. preterm infants 29 to 35 weeks' gestational age (wGA) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (RSV) disease and not receiving RSV immunoprophylaxis during the 2014 to 2015 RSV season. Study Design This is a noninterventional, observational, cohort study. Results A total of 702 infants were hospitalized with community-acquired RSV disease, of whom an estimated 42% were admitted to the intensive care unit (ICU) and 20% required invasive mechanical ventilation (IMV). Earlier gestational age and younger chronologic age were associated with an increased frequency of RSV-confirmed hospitalization (RSVH), ICU admission, and IMV. Among infants 29 to 32 wGA and < 3 months of age, 68% required ICU admission and 44% required IMV. One death occurred of an infant 29 wGA. Among the 212 infants enrolled for in-depth analysis of health care resource utilization, mean and median RSVH charges were $55,551 and $27,461, respectively, which varied by intensity of care required. Outpatient visits were common, with 63% and 62% of infants requiring visits before and within 1 month following the RSVH, respectively. Conclusion Preterm infants 29 to 35 wGA are at high risk for severe RSV disease, which imposes a substantial health burden, particularly in the first months of life.

The Logistics and Coordination of Respiratory Syncytial Virus Immunoprophylaxis Use Among US Pediatric Specialists.

This study was conducted to survey US pediatric specialists about administration of respiratory syncytial virus (RSV) immunoprophylaxis, communication patterns among physicians and parents, and barriers to access. Separate surveys were sent to neonatologists, pediatricians, pediatric pulmonologists, and pediatric cardiologists. Most physicians (≥93.5%) routinely recommended immunoprophylaxis to high-risk children. Most respondents (≥71.8%) reported that >50.0% of eligible infants and young children received each monthly dose throughout the RSV season, with the first dose most commonly administered before discharge from the birth hospitalization. To ensure receipt of subsequent doses, specialists frequently scheduled a follow-up visit at the end of the current appointment. All specialists reported insurance denials as the biggest obstacle to the administration of immunoprophylaxis to high-risk children. These findings may be used to improve adherence to immunoprophylaxis by enhancing education and physician-parent communications about severe RSV disease prevention, and by reducing known barriers to use of this preventive therapy.

Perceived Risk of Severe Respiratory Syncytial Virus Disease and Immunoprophylaxis Use Among US Pediatric Specialists.

This study was conducted to assess the perception of US pediatric specialists of respiratory syncytial virus (RSV) disease risk and determine their clinical practices regarding immunoprophylaxis for high-risk children. Separate surveys were sent to neonatologists, pediatricians, pediatric pulmonologists, and pediatric cardiologists. Data were collected using structured questions requiring quantitative responses. Most neonatologists and pediatricians (>82.7%) reported a high clinical need for RSV immunoprophylaxis in preterm infants <32 weeks' gestational age. Pediatric pulmonologists and pediatric cardiologists suggested that health conditions indicative of chronic lung disease of prematurity and hemodynamically significant congenital heart disease, respectively, confer eligibility for RSV immunoprophylaxis. Agreement with the changes in the 2014 American Academy of Pediatrics guidance for RSV immunoprophylaxis was mixed among respondents from the 4 specialties. Survey findings may provide a basis to improve education about risk for severe RSV disease and evaluate changes in physician use of RSV immunoprophylaxis based on the 2014 guidance.

Receipt of palivizumab before birth hospitalization discharge among preterm infants in the United States.

OBJECTIVE: This study aims to determine predischarge palivizumab receipt prevalence among infants ≤ 36 weeks' gestational age. STUDY DESIGN: This retrospective cohort study used hospital discharge records from the Premier Perspective database (Premier Inc., Charlotte, NC) of infants ≤ 36 weeks' gestational age who were discharged home after birth hospitalization during the November-March respiratory syncytial virus (RSV) seasons from 2006 to 2011. Descriptive statistics were performed and logistic regression was employed to identify differences in categorical variables. RESULTS: Among infants ≤ 36 weeks' gestational age discharged home during the RSV seasons, 21.4 to 27.0% had a record of palivizumab receipt before discharge. Among infants ≤ 30 weeks' gestational age, palivizumab receipt was 82.3 to 88.8%. Receipt varied considerably at the hospital level, from 0 to 100%. CONCLUSION: This study improves our understanding of characteristics associated with predischarge palivizumab administration. The identified gaps in recommended care can help inform future implementation of palivizumab and other interventions to help improve the health of high-risk preterm infants in the United States.

A population-weighted, condition-adjusted estimate of palivizumab efficacy in preventing RSV-related hospitalizations among US high-risk children.

Preterm infants ≤ 35 weeks' gestational age (GA), and children ≤ 24 months of age with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital heart disease (hsCHD) are at high risk for developing severe respiratory syncytial virus (RSV) disease. In 3 previous randomized, placebo-controlled trials, palivizumab efficacy varied significantly based on these underlying conditions, and trial enrollment was not proportional to condition prevalence. This analysis provides the first estimate of the population-weighted efficacy of palivizumab in high-risk children, adjusting for condition prevalence. Palivizumab efficacy by high-risk condition was obtained from the clinical trials. The annual number of US children with each condition was obtained from the 2010 Centers for Disease Control and Prevention (CDC) natality statistics and the medical literature. Data from specialty pharmacies in the US palivizumab distribution network were used to estimate the population for each condition receiving at least 1 dose in the outpatient setting in 2012-2013. The weighted efficacy estimate was derived by summing the products of the condition-specific relative risk reductions and the relative frequency of each condition among those receiving palivizumab. The US population-weighted efficacy estimate for those receiving palivizumab was 68%. Due to the low prevalence of BPD and hsCHD and the higher efficacy observed in preterm infants without BPD or CHD, the population-weighted estimate of palivizumab efficacy is higher than the overall 45-55% efficacy observed in initial clinical trials. Consistent with 2012 American Academy of Pediatrics RSV prophylaxis recommendations, a low proportion of preterm infants 32-35 weeks' gestational age receive palivizumab.

Serum palivizumab level is associated with decreased severity of respiratory syncytial virus disease in high-risk infants.

Monthly doses of palivizumab, an RSV-specific monoclonal antibody, reduce RSV-related hospitalizations (RSVH) in high-risk children; however, no specific palivizumab level has been correlated with disease severity in humans. A post hoc analysis of a previous randomized, placebo-controlled trial evaluated the relationship between serum palivizumab level at the time of RSVH and disease severity. Pediatric intensive care unit (PICU) admission was the primary severity marker. Relationships were evaluated between disease severity and gestational age, age at enrollment, age at RSVH, presence of bronchopulmonary dysplasia, sex, race, multiple birth, household smoking, daycare attendance, sibling(s), family history of atopy, duration between most recent palivizumab dose and RSVH, and palivizumab level at RSVH. Forty-two (87.5%) of 48 palivizumab recipients with RSVH had palivizumab levels drawn; 11 were admitted to the PICU. Mean palivizumab levels were lower in PICU-admitted subjects (47.2 µg/mL) vs. non-PICU subjects (98.7 µg/mL; P < 0.0001); there were no statistically significant differences in other variables examined. The probability of PICU admission declined with higher palivizumab levels; there were no PICU admissions with levels ≥ 92 µg/mL. In multivariate analyses, palivizumab level was the only independent predictor of PICU admission (P = 0.009). Palivizumab level also correlated with duration of RSVH and PICU stay, supplemental oxygen use and duration, and mechanical ventilation use and duration (P < 0.05). Higher palivizumab level was associated with decreased disease severity in high-risk infants with RSVH. Findings suggest that palivizumab level has clinical relevance, and adherence to timely monthly dosing may confer additional protection among high-risk children receiving palivizumab.

Respiratory syncytial virus surveillance in the United States, 2007-2012: results from a national surveillance system.

BACKGROUND: Annual respiratory syncytial virus (RSV) outbreaks throughout the US exhibit variable patterns in onset, peak month of activity and duration of season. RSVAlert, a US surveillance system, collects and characterizes RSV test data at national, regional, state and local levels. METHODS: RSV test data from 296 to 666 laboratories from 50 states, the District of Columbia and Puerto Rico (as of 2010) were collected during the 2007-2008 to 2011-2012 RSV seasons. Data were collected in early August/September to the following August/September each season. Participating laboratories provided the total number and types of RSV tests performed each week and test results. RSV season onset and offset were defined as the first and last, respectively, of 2 consecutive weeks during which the mean percentage of specimens testing positive for RSV was ≥10%. RESULTS: Nationally, the RSV season onset occurred in October/November of each year with offset occurring in March/April of the following year. The RSV season averaged 20 weeks and typically occurred earliest in the South and latest in the West. The onset, offset and duration varied considerably within the U.S. Department of Health and Human Services regions. RSV activity in Puerto Rico was elevated throughout the 2-year period studied. Median onset in core-based statistical areas ranged from 2 weeks earlier to 5 weeks later than those in their corresponding states. CONCLUSIONS: Substantial variability existed in the timing of RSV activity at all geographic strata analyzed. RSV actively circulated (ie, ≥10%) in many areas outside the traditionally defined RSV epidemic period of November to March.

Laboratory testing trends for respiratory syncytial virus, 2007-2011.

BACKGROUND: Antigen detection tests have been the most common diagnostic assay used to detect and diagnose respiratory syncytial virus (RSV). The utility and increased sensitivity of polymerase chain reaction (PCR) tests have been reported; however, their use in US hospital laboratories is not well characterized. OBJECTIVE: To describe changes in RSV test types used by US hospital-affiliated laboratories, focusing on PCR testing prevalence. STUDY DESIGN: Data were collected from 480 to 666 laboratories each RSV season (2007-2008 through 2010-2011) across 50 states, the District of Columbia, and Puerto Rico. A descriptive analysis was conducted using this convenience sample of RSV tests conducted from November to April each season. Total numbers and types of RSV tests performed were reported weekly and weekly proportions by test type were calculated. Kendall τ rank correlation was used to quantify associations between time and proportions of each test type. RESULTS: PCR tests accounted for 2%, 3%, 16%, and 21% of weekly tests (total range, 381,068-481,654 over 4 seasons) conducted each season from 2007 to 2011, respectively. The proportion of laboratories reporting ≥1 PCR tests was 4%, 5%, 10%, and 16%, respectively. Decreases in antigen testing and viral culture were similarly observed. CONCLUSIONS: Although antigen detection was the predominant test type reported in the sample of US hospital laboratories for RSV testing, PCR use increased to >20% of tests reported. These results demonstrate the increasing contribution of PCR to RSV surveillance. RSV surveillance systems relying solely on antigen detection results will not capture an increasing proportion of RSV test results.