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BackgroundDiagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear.MethodsThis multinational observational cohort study enrolled patients aged >120 days and

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. [ABSTRACT FROM AUTHOR]

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z -scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552–679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93–1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19–0.64; P  = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions. [ABSTRACT FROM AUTHOR]