Immunogenicity and safety of Sinovac-CoronaVac booster vaccinations in 12-17- year-olds with clinically significant reactions from Pfizer-BNT162b2 vaccination.

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.

Febrile infants risk score at triage (FIRST) for the early identification of serious bacterial infections.

We aimed to derive the Febrile Infants Risk Score at Triage (FIRST) to quantify risk for serious bacterial infections (SBIs), defined as bacteremia, meningitis and urinary tract infections. We performed a prospective observational study on febrile infants < 3 months old at a tertiary hospital in Singapore between 2018 and 2021. We utilized machine learning and logistic regression to derive 2 models: FIRST, based on patient demographics, vital signs and history, and FIRST + , adding laboratory results to the same variables. SBIs were diagnosed in 224/1002 (22.4%) infants. Among 994 children with complete data, age (adjusted odds ratio [aOR] 1.01 95%CI 1.01-1.02, p < 0.001), high temperature (aOR 2.22 95%CI 1.69-2.91, p < 0.001), male sex (aOR 2.62 95%CI 1.86-3.70, p < 0.001) and fever of ≥ 2 days (aOR 1.79 95%CI 1.18-2.74, p = 0.007) were independently associated with SBIs. For FIRST + , abnormal urine leukocyte esterase (aOR 16.46 95%CI 10.00-27.11, p < 0.001) and procalcitonin (aOR 1.05 95%CI 1.01-1.09, p = 0.009) were further identified. A FIRST + threshold of ≥ 15% predicted risk had a sensitivity of 81.8% (95%CI 70.5-91.0%) and specificity of 65.6% (95%CI 57.8-72.7%). In the testing dataset, FIRST + had an area under receiver operating characteristic curve of 0.87 (95%CI 0.81-0.94). These scores can potentially guide triage and prioritization of febrile infants.

Adding heart rate n-variability (HRnV) to clinical assessment potentially improves prediction of serious bacterial infections in young febrile infants at the emergency department: a prospective observational study.

Background: We aim to investigate the utility of heart rate variability (HRV) and heart rate n-variability (HRnV) in addition to vital signs and blood biomarkers, among febrile young infants at risk of serious bacterial infections (SBIs). Methods: We performed a prospective observational study between December 2017 and November 2021 in a tertiary paediatric emergency department (ED). We included febrile infants <90 days old with a temperature ≥38 ℃. We obtained HRV and HRnV parameters via a single lead electrocardiogram. HRV measures beat-to-beat (R-R) oscillation and reflects autonomic nervous system (ANS) regulation. HRnV includes overlapping and non-overlapping R-R intervals and provides additional physiological information. We defined SBIs as meningitis, bacteraemia and urinary tract infections (UTIs). We performed area under curve (AUC) analysis to assess predictive performance. Results: We recruited 330 and analysed 312 infants. The median age was 35.5 days (interquartile range 13.0-61.0); 74/312 infants (23.7%) had SBIs with the most common being UTIs (66/72, 91.7%); 2 infants had co-infections. No patients died and 32/312 (10.3%) received fluid resuscitation. Adding HRV and HRnV to demographics and vital signs at ED triage successively improved the AUC from 0.765 [95% confidence interval (CI): 0.705-0.825] to 0.776 (95% CI: 0.718-0.835) and 0.807 (95% CI: 0.752-0.861) respectively. The final model including demographics, vital signs, HRV, HRnV and blood biomarkers had an AUC of 0.874 (95% CI: 0.828-0.921). Conclusions: Addition of HRV and HRnV to current assessment tools improved the prediction of SBIs among febrile infants at ED triage. We intend to validate our findings and translate them into tools for clinical care in the ED.

Validation and comparison of the PECARN rule, Step-by-Step approach and Lab-score for predicting serious and invasive bacterial infections in young febrile infants.

INTRODUCTION: Differentiating infants with serious bacterial infections (SBIs) or invasive bacterial infections (IBIs) from those without remains a challenge. We sought to compare the diagnostic performances of single biomarkers (absolute neutrophil count [ANC], C-reactive protein [CRP] and procalcitonin [PCT]) and 4 diagnostic approaches comprising Lab-score, Step-by-Step approach (original and modified) and Pediatric Emergency Care Applied Research Network (PECARN) rule. METHOD: This is a prospective cohort study involving infants 0-90 days of age who presented to an emergency department from July 2020 to August 2021. SBIs were defined as bacterial meningitis, bacteraemia and/or urinary tract infections. IBIs were defined as bacteraemia and/or bacterial meningitis. We evaluated the performances of Lab-score, Step-by-Step (original and modified) and PECARN rule in predicting SBIs and IBIs. RESULTS: We analysed a total of 258 infants, among whom 86 (33.3%) had SBIs and 9 (3.5%) had IBIs. In predicting SBIs, ANC ≥4.09 had the highest sensitivity and negative predictive value (NPV), while PCT ≥1.7 had the highest specificity and positive predictive value (PPV). CRP ≥20 achieved the highest area under receiver operating characteristic curve (AUC) of 0.741 (95% confidence interval [CI] 0.672-0.810). The Step-by-Step (original) approach had the highest sensitivity (97.7%). Lab-score had the highest AUC of 0.695 (95% CI 0.621-0.768), compared to PECARN rule at 0.625 (95% CI 0.556-0.694) and Step-by-Step (original) at 0.573 (95% CI 0.502-0.644). In predicting IBIs, PCT ≥1.7 had the highest sensitivity, specificity, PPV and NPV. The Step-by-Step (original and modified) approach had the highest sensitivity of 100%. Lab-score had the highest AUC of 0.854 (95% CI 0.731-0.977) compared to PECARN rule at 0.589 (95% CI 0.420-0.758) and Step-by-Step at 0.562 (95% CI 0.392-0.732). CONCLUSION: CRP strongly predicted SBIs, and PCT strongly predicted IBI. The Step-by-Step approach had the highest sensitivity and NPV, while Lab-score had the highest specificity and AUC in predicting SBIs and IBIs.

Delays in Time-To-Antibiotics for Young Febrile Infants With Serious Bacterial Infections: A Prospective Single-Center Study.

Introduction: Fear of missed serious bacterial infections (SBIs) results in many febrile young infants receiving antibiotics. We aimed to compare the time to antibiotics between infants with SBIs and those without. Materials and Methods: We recruited febrile infants ≤ 90 days old seen in the emergency department (ED) between December 2017 and April 2021. SBI was defined as (1) urinary tract infection, (2) bacteremia or (3) bacterial meningitis. We compared the total time (median with interquartile range, IQR) from ED arrival to infusion of antibiotics, divided into (i) time from triage to decision for antibiotics and (ii) time from decision for antibiotics to administration of antibiotics. Results: We analyzed 81 and 266 infants with and without SBIs. Median age of those with and without SBIs were 44 (IQR 19-72) and 29 (IQR 7-56) days, respectively (p = 0.002). All infants with SBIs and 168/266 (63.2%) infants without SBIs received antibiotics. Among 249 infants who received antibiotics, the median total time from ED arrival to infusion of antibiotics was 277.0 (IQR 236.0-385.0) mins for infants with SBIs and 304.5 (IQR 238.5-404.0) mins for those without (p = 0.561). The median time to decision for antibiotics was 156.0 (IQR 115.0-255.0) mins and 144.0 (IQR 105.5-211.0) mins, respectively (p = 0.175). Following decision for antibiotics, infants with SBIs received antibiotics much faster compared to those without [107.0 (IQR 83.0-168.0) vs. 141.0 (94.0-209.5) mins, p = 0.017]. Conclusion: There was no difference in total time taken to antibiotics between infants with SBIs and without SBIs. Both recognition and administration delays were observed. While all infants with SBIs were adequately treated, more than half of the infants without SBIs received unnecessary antibiotics. This highlights the challenge in managing young febrile infants at initial presentation, and demonstrates the need to examine various aspects of care to improve the overall timeliness to antibiotics.

Predictors of serious bacterial infections using serum biomarkers in an infant population aged 0 to 90 days: a prospective cohort study.

Objective: Young febrile infants represent a vulnerable population at risk for serious bacterial infections (SBI). We aimed to evaluate the diagnostic accuracy of components of the complete blood count in comparison with C-reactive protein (CRP) to predict SBI among febrile infants. Design and setting: Prospective cohort study conducted in a tertiary emergency department between December 2018 and November 2019. Patients: We included febrile infants ≤3 months old with complete blood count results. We analysed their white blood cell count (WBC), absolute neutrophil ratio (ANC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet count ratio, and compared these to the performance of CRP. Main outcome measures: SBIs were defined as urinary tract infection, bacteraemia, bacterial meningitis, sepsis, pneumonia, skin and soft tissue infection, bacterial enteritis, septic arthritis or osteomyelitis. Results: Of the 187 infants analysed, 54 (28.9%) were diagnosed with SBI. Median values of WBC, ANC, NLR and CRP were significantly higher in infants with SBI: WBC (13.8 vs 11.4×109/L, p=0.004), ANC (6.7 vs 4.1×109/L, p<0.001), NLR (1.3 vs 0.9, p=0.001) and CRP (21.0 vs 2.3 mg/L, p<0.001), compared with those without. CRP had the best discriminatory values for SBI, with area under the curve (AUC) of 0.815 (95% CI 0.747 to 0.883), compared with WBC, ANC and NLR. A predictive model consisting of WBC, ANC and NLR in combination with clinical parameters, had an AUC of 0.814 (95% CI 0.746 to 0.883). There was increased discriminative performance when this predictive model was combined with CRP, (AUC of 0.844, 95% CI 0.782 to 0.906). Conclusion: In young febrile infants, CRP was the best discriminatory biomarker for SBI. WBC, ANC and NLR when used in combination have potential diagnostic utility in this population.

Early prediction of serious infections in febrile infants incorporating heart rate variability in an emergency department: a pilot study.

BACKGROUND: Early differentiation of febrile young infants with from those without serious infections (SIs) remains a diagnostic challenge. We sought to (1) compare vital signs and heart rate variability (HRV) parameters between febrile infants with versus without SIs, (2) assess the performance of HRV and vital signs with reference to current triage tools and (3) compare HRV and vital signs to HRV, vital signs and blood biomarkers, when predicting for the presence of SIs. METHODS: Using a prospective observational design, we recruited patients <3 months old presenting to a tertiary paediatric ED in Singapore from December 2018 through November 2019. We obtained patient demographic characteristics, triage assessment (including the Severity Index Score (SIS)), HRV parameters (time, frequency and non-linear domains) and laboratory results. We performed multivariable logistic regression analyses to predict the presence of an SI, using area under the curve (AUC) with the corresponding 95% CI to assess predictive capability. RESULTS: Among 203 infants with a mean age of 38.4 days (SD 27.6), 67 infants (33.0%) had an SI. There were significant differences in the time, frequency and non-linear domains of HRV parameters between infants with versus without SIs. In predicting SIs, gender, temperature and the HRV non-linear parameter Poincaré plot SD2 (AUC 0.78, 95% CI 0.71 to 0.84) performed better than SIS alone (AUC 0.61, 95% CI 0.53 to 0.68). Model performance improved with the addition of absolute neutrophil count and C reactive protein (AUC 0.82, 95% CI 0.76 to 0.89). CONCLUSION: An exploratory prediction model incorporating HRV and biomarkers improved prediction of SIs. Further research is needed to assess if HRV can identify which young febrile infants have an SI at ED triage. TRIAL REGISTRATION NUMBER: NCT04103151.

Parental knowledge and beliefs on the use of child car restraints in Singapore: a qualitative study.

INTRODUCTION: Road traffic injuries and fatalities represent a significant public health problem. In Singapore, compliance with appropriate child car restraints (CCRs) is poor. We aimed to understand parental knowledge, beliefs and barriers regarding the use of CCRs. METHODS: In this qualitative study, we conducted five focus group discussions with parents who drive with their children in private cars. Participants were recruited using the KK Women's and Children's Hospital's social media page. Guiding questions were derived by consensus following literature review and adaptation to the Singapore context, exploring parental perceptions of CCR use. Focus group interviews were then transcribed and analysed. RESULTS: 33 participants were recruited, with an age range of 28‒46 (mean age 35.5) years. They had a total of 46 children with ages ranging from 2.5 months to 14 years (mean age 4.2 years). Three key themes were identified: parental knowledge regarding CCRs, barriers to CCR use, and suggestions to increase CCR compliance. Barriers to compliance included lack of knowledge, difficult child behaviour and cultural norms. A multipronged approach was proposed to increase CCR use, including educating the public, reinforcing positive behaviour, legal enforcement as a deterrent to non-compliance, increasing CCR installation services, providing CCRs for taxi users and offering financial incentives. CONCLUSION: Non-compliance to CCR use is multidimensional, including multiple potentially modifiable factors. This study could inform ongoing collaborative injury prevention efforts among healthcare professionals, industry partners and the traffic police, using public education and outreach to reduce the burden of road traffic injuries.