The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

Clinical characteristics and outcomes of children with single or co-detected rhinovirus-associated acute respiratory infection in Middle Tennessee.

BACKGROUND: Rhinovirus (RV) is one of the most common etiologic agents of acute respiratory infection (ARI), which is a leading cause of morbidity and mortality in young children. The clinical significance of RV co-detection with other respiratory viruses, including respiratory syncytial virus (RSV), remains unclear. We aimed to compare the clinical characteristics and outcomes of children with ARI-associated RV-only detection and those with RV co-detection-with an emphasis on RV/RSV co-detection. METHODS: We conducted a prospective viral surveillance study (11/2015-7/2016) in Nashville, Tennessee. Children < 18 years old who presented to the emergency department (ED) or were hospitalized with fever and/or respiratory symptoms of < 14 days duration were eligible if they resided in one of nine counties in Middle Tennessee. Demographics and clinical characteristics were collected by parental interviews and medical chart abstractions. Nasal and/or throat specimens were collected and tested for RV, RSV, metapneumovirus, adenovirus, parainfluenza 1-4, and influenza A-C using reverse transcription quantitative polymerase chain reaction assays. We compared the clinical characteristics and outcomes of children with RV-only detection and those with RV co-detection using Pearson's χ2 test for categorical variables and the two-sample t-test with unequal variances for continuous variables. RESULTS: Of 1250 children, 904 (72.3%) were virus-positive. RV was the most common virus (n = 406; 44.9%), followed by RSV (n = 207; 19.3%). Of 406 children with RV, 289 (71.2%) had RV-only detection, and 117 (28.8%) had RV co-detection. The most common virus co-detected with RV was RSV (n = 43; 36.8%). Children with RV co-detection were less likely than those with RV-only detection to be diagnosed with asthma or reactive airway disease both in the ED and in-hospital. We did not identify differences in hospitalization, intensive care unit admission, supplemental oxygen use, or length of stay between children with RV-only detection and those with RV co-detection. CONCLUSION: We found no evidence that RV co-detection was associated with poorer outcomes. However, the clinical significance of RV co-detection is heterogeneous and varies by virus pair and age group. Future studies of RV co-detection should incorporate analyses of RV/non-RV pairs and include age as a key covariate of RV contribution to clinical manifestations and infection outcomes.

Post-operative opioid analgesic prescribing patterns in gynecologic oncology patients following the implementation of a statewide -prescription monitoring and reporting system.

OBJECTIVE: To analyze the effect of the Connecticut Prescription Monitoring and Reporting System (CPMRS) on the number of opioid tablets prescribed to gynecologic oncology patients post-operatively. DESIGN/PARTICIPANTS: This was a retrospective chart review of patients who received surgery for suspicious masses, premalignant, or malignant conditions of uterus, tubes, ovaries, or cervix. Charts were divided into two groups before and after the implementation of an updated prescription monitoring system in July 2016. Quantitative data were collected on the number of opioids prescribed from hospital discharge summaries. Qualitative data included prescription and/or -recommendation of nonopioid analgesics and type of procedure (open versus minimally invasive). Demographic information included age, ethnicity, and insurance coverage. OUTCOMES: We identified a statistically significant, 50 percent decrease in opioid tablets in the After July 2016 group (n = 226) compared with the Before July 2016 group (n = 136) (p < 0.001). As anticipated, fewer opioid tablets were prescribed following minimally invasive procedures compared to open cases (p = 0.007). On examining nonopioid analgesic data, we found more patients received a prescription for nonopioid analgesics in the After July 2016 group compared with the Before July 2016 group (p < 0.001). CONCLUSION: This study confirms a decrease in opioid tablets prescribed to post-operative gynecologic oncology patients since July 2016. This difference cannot be attributed to the implementation of the CPMRS alone, but chronologically relates to updated requirements. Additionally, our results re-emphasize that minimally invasive surgery has a reduced number of prescribed opioids. A multi-institutional study is required with more patients to detail the factors involved in further decreasing opioid prescribing.

Behavioral and neuroanatomical outcomes in a rat model of preterm hypoxic-ischemic brain Injury: Effects of caffeine and hypothermia.

The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981). This preparation models brain injury seen in premature infants (gestational age (GA) 32-35 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language/learning disabilities. To assess therapies that might offer translational potential for improved outcomes, we used a P6 HI rat model to measure the behavioral and neuroanatomical effects of two prospective preterm neuroprotective treatments - hypothermia and caffeine. Hypothermia (aka "cooling") is an approved and moderately efficacious intervention therapy for fullterm infants with perinatal hypoxic-ischemic (HI) injury, but is not currently approved for preterm use. Caffeine is a respiratory stimulant used during removal of infants from ventilation but has shown surprising long-term benefits, leading to consideration as a therapy for HI of prematurity. Current findings support caffeine as a preterm neuroprotectant; treatment significantly improved some behavioral outcomes in a P6 HI rat model and partially rescued neuropathology. Hypothermia treatment (involving core temperature reduction by 4 °C for 5 h), conversely, was found to be largely ineffective and even deleterious for some measures in both HI and sham rats. These results have important implications for therapeutic intervention in at-risk preterm populations, and promote caution in the application of hypothermia protocols to at-risk premature infants without further research.