Corrigendum: Wastewater-based surveillance identifies start to the pediatric respiratory syncytial virus season in two cities in Ontario, Canada.

[This corrects the article DOI: 10.3389/fpubh.2023.1261165.].

Wastewater-based surveillance identifies start to the pediatric respiratory syncytial virus season in two cities in Ontario, Canada.

Introduction: Detection of community respiratory syncytial virus (RSV) infections informs the timing of immunoprophylaxis programs and hospital preparedness for surging pediatric volumes. In many jurisdictions, this relies upon RSV clinical test positivity and hospitalization (RSVH) trends, which are lagging indicators. Wastewater-based surveillance (WBS) may be a novel strategy to accurately identify the start of the RSV season and guide immunoprophylaxis administration and hospital preparedness. Methods: We compared citywide wastewater samples and pediatric RSVH in Ottawa and Hamilton between August 1, 2022, and March 5, 2023. 24-h composite wastewater samples were collected daily and 5 days a week at the wastewater treatment facilities in Ottawa and Hamilton, Ontario, Canada, respectively. RSV WBS samples were analyzed in real-time for RSV by RT-qPCR. Results: RSV WBS measurements in both Ottawa and Hamilton showed a lead time of 12 days when comparing the WBS data set to pediatric RSVH data set (Spearman's ρ = 0.90). WBS identify early RSV community transmission and declared the start of the RSV season 36 and 12 days in advance of the provincial RSV season start (October 31) for the city of Ottawa and Hamilton, respectively. The differing RSV start dates in the two cities is likely associated with geographical and regional variation in the incidence of RSV between the cities. Discussion: Quantifying RSV in municipal wastewater forecasted a 12-day lead time of the pediatric RSVH surge and an earlier season start date compared to the provincial start date. These findings suggest an important role for RSV WBS to inform regional health system preparedness, reduce RSV burden, and understand variations in community-related illness as novel RSV vaccines and monoclonal antibodies become available.

Impact of level of neonatal care on phlebotomy and blood transfusion in extremely low birthweight infants: a prospective, multicenter, observational study.

Objectives: To explore the level of neonatal care on cumulative phlebotomy loss (cPL) and red cell transfusions in extremely low birthweight [ELBW; birthweight (BW) <1,000 g] infants, up to 40 weeks post-conceptual age (PCA). The secondary objective was to determine the associations between cPL and number of transfusions and between transfusions and hospital outcomes. Methods: A prospective, comparative, observational study was conducted in two level IV and two level III neonatal intensive care units (NICUs) in Thailand. Daily cPL volume and number of blood tests were recorded. Descriptive data are reported as frequency and percentage for categorical variables and median [25th percentile (P25), 75th percentile (P75)] for continuous data according to the data distribution. A p-value <0.05 was considered statistically significant. Results: 210 ELBW infants were included; 99 and 111 were admitted to level IV and level III NICUs, respectively. Birth weight of level IV infants was lower 780.0 [660.0, 875.0] vs. 865.0 [723.0, 930.0] g; p < 0.001]. Initial group hematocrits were similar (43.1% vs. 44.0%, p = 0.47). cPL for each infant was 28.1 [16.5, 46.4] ml. Level IV infants had more tests (n = 89 [54, 195] vs. 59 [37, 88], p < 0.001). Counterintuitively, there was a lower cPL trend in level IV infants, but this was insignificant (19.6 [12.3, 52.3] vs. 28.9 [19.3, 45.3] ml; p = 0.06). The number of transfusions in both NICUs was similar 4 [2, 6], with a strong correlation between cPL and number of transfusions (r = 0.79, p < 0.001). Transfusions were significantly associated with bronchopulmonary dysplasia [BPD; adjusted RR (95% CI): 2.6 (1.2, 5.3), p = 0.01]. Conclusions: Level IV NICUs conducted more blood tests in ELBW infants without a difference in cPL, and number of transfusions. Cumulative PL correlated with number of transfusions and was associated with BPD risk. Minimizing cPL by point-of-care tests and restrictive transfusion criteria, may reduce need for transfusion.

Comparison of the SenSmart™ and the INVOS™ neonatal cerebral near-infrared spectrometry devices.

Objectives: To determine the correlation and agreement between the SenSmart™ and the INVOS™ devices of neonatal cerebral regional oxygen saturation (CrSO2) measurements using neonatal sensors. The secondary objective was to develop a regression model that predicts CrSO2-INVOS values using CrSO2-SenSmart indices and determine whether the values between the devices are interchangeable. Methods: A prospective, cross-sectional study was conducted in infants during the first 4 weeks of life. Simultaneous, bilateral CrSO2 was measured using the SenSmart™X100 (CrSO2-SenSmart) or INVOS™ 5100C (CrSO2-INVOS) device in each frontoparietal area for 2 h. Five-minute CrSO2 values were extracted for analysis. Results: Thirty infants were recruited with 720 pairwise measurements and 26 (84%) were evaluated in the first week of life. Mean gestational age of the preterm and term infants was [30.9 ± 2.8 (n = 14) and 38.8 ± 1.1 (n = 16)] weeks, respectively. Overall CrSO2- was 77.08 ± 9.70% and 71.45 ± 12.74% for the SenSmart and INVOS, respectively (p < 0.001). The correlation coefficient (r) between the CrSO2-SenSmart and INVOS was 0.20 (p < 0.001). The mean difference between the CrSO2-SenSmart and INVOS was 5.63 ± 13.87% with -21.6% to 32.8% limits of agreement. The r and mean difference was 0.39 (p < 0.001) and 8.87 ± 12.58% in preterm infants, and 0.06 (p = 0.27) and 2.79 ± 14.34 in term infants. Conclusion: The CrSO2-SenSmart tended to read higher than the CrSO2-INVOS device. There was no correlation between the CrSO2-SenSmart and the CrSO2-INVOS in term infants and it was weak in preterms. Due to imprecise agreement, the CrSO2-SenSmart values are not interchangeable with those of the CrSO2-INVOS.

Understanding Policy Decisions and Their Implications Regarding Preventive Interventions for Respiratory Syncytial Virus (RSV) Infection in Canadian Infants: A Primer for Nurses.

Respiratory syncytial virus (RSV) is a leading cause of morbidity and hospitalization in young children, and prevention is the primary management strategy. At present, palivizumab, a monoclonal antibody providing immediate passive immunity, rather than a vaccine that induces active immunity, is the only preventive intervention used in routine practice internationally. In Canada, access varies across the country. Prophylaxis policies are mainly driven by cost-effectiveness analyses, and it is crucial that the full costs and benefits of any intervention are captured. Positive results from a new Canadian cost-effectiveness analysis of palivizumab will help address the current inequality in use while providing a framework for future models of RSV preventives. Nurses are the principal educators for parents about the risks of childhood RSV and optimal prevention via basic hygiene, behavioral and environmental measures, and seasonal prophylaxis. Nurses should be provided not only with regular, up-to-date, and accurate information on RSV and the clinical aspects of emerging interventions but be informed on the decision-making governing the use of preventive strategies.

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.

Effects of antenatal dexamethasone on postnatal serum cortisol levels in late preterm infants.

OBJECTIVES: To explore whether antenatal dexamethasone impacts postnatal serum cortisol levels in stable late preterm (LPT) infants. Secondary outcomes were to identify short-term hospital outcomes related to antenatal dexamethasone exposure. METHODS: A prospective cohort study of serial serum cortisol levels in LPT infants within 3 h of birth, and at 1, 3, and 14 postnatal days. Serum cortisol levels were compared between infants exposed to antenatal dexamethasone >3 h and <14 days prior to delivery (aDex) and those who either did not receive dexamethasone or were exposed < 3 h or >14 days prior to delivery (no-aDex). RESULTS: Thirty-two LPT infants (aDex) were compared with 29 infants (no-aDEX). Group demographic characteristics were similar. Serum cortisol levels were identical between the groups at all 4-time points. Cumulative antenatal dexamethasone exposure ranged from 0 to 12 doses. Post-hoc analysis of the 24-hour serum cortisol levels indicated a significant difference between 1 to 3 cumulative doses versus 4 or more doses (p = .01). Only 1 infant in the aDex group had a cortisol level <3rd percentile of the reference value. Rates of hypoglycemia (absolute difference [95% CI] - 1.0 [-16.0,15.0]; p = .90) and mechanical ventilation were similar in both groups (absolute difference [95%CI] - 0.3 [-9.3,8.7]; p = .94). No deaths occurred. CONCLUSION: Antenatal dexamethasone administered 14 days prior to delivery did not affect serum cortisol levels and short-term hospital outcomes in stable LPT infants. Exposure to low cumulative doses of dexamethasone resulted in transient low serum cortisol levels compared to 4 or more doses only at 24-hours.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.

BACKGROUND AND OBJECTIVE: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST). METHODS: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included. RESULTS: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231). CONCLUSIONS: Palivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

Perspective: the potential of wastewater-based surveillance as an economically feasible game changer in reducing the global burden of pediatric respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the leading viral cause of childhood bronchiolitis and pneumonia causing over 3 million hospitalizations and 100,000 deaths in children under 5 years of age annually. Wastewater-based surveillance (WBS) has proven an effective early warning system for high-consequence pathogens, including SARS-CoV-2, polio, mpox, and influenza, but has yet to be fully leveraged for RSV surveillance. A model predicated on the Canadian province of Ontario demonstrates that implementation of a WBS system can potentially result in significant cost savings and clinical benefits when guiding an RSV preventive program with a long-acting monoclonal antibody. A network of integrated WBS initiatives offers the opportunity to help minimize the devastating global burden of RSV in children by optimizing the timing of preventive measures and we strongly advocate that its benefits continue to be explored.

De Novo Heterozygous Mutation in FGFR2 Causing Type II Pfeiffer Syndrome.

Pfeiffer syndrome (PS) is an autosomal dominant disorder with three subtypes stemming from heterozygous mutations in the fibroblast growth factors FGFR1 and FGFR2. The subtypes overlap with heterogeneous clinical manifestations and variable prognosis dependent on neurological and respiratory compromise that impact short- and long-term outcomes and survival. We present a male, term infant with type II PS that was diagnostically suspected antenatally based on three-dimensional ultrasonographic findings that were confirmed postnatally by craniofacial tomography and magnetic resonance imaging. A new generation sequencing panel identified a unique de novo FGFR2, c.335 A > G p. Tyr112Cys variant, the first of its kind, and features that closely aligned with subtype II PS. Initial molecular results categorized the mutation as nonpathogenic, but it was later reclassified as pathogenic. Antenatal, multidisciplinary parental counseling about the tentative diagnosis and prognosis facilitated postnatal decisions that culminated in an informed choice for palliative care and early demise.

Assessment of Nurses' Knowledge and Confidence Regarding Tracheostomy Care in a Pediatric Long Term Care Hospital in Saudi Arabia.

Background: The incidence of tracheostomy insertion in pediatric patients has increased over the last few decades. Tracheostomized pediatric patients need daily, meticulous care by qualified nurses to minimize severe, avoidable complications. Adequately trained nurses facilitate patients' stability, accelerate weaning from the ventilator, and reduce potential tracheostomy dislodgement. Methods: A cross-sectional, retrospective cohort survey was conducted in September 2021, using an electronic version of a self-questionnaire, to assess nurses' knowledge and comfort level regarding tracheostomy care of pediatric patients at the International Extended Care Center in Jeddah, Saudi Arabia. Statistical analysis of the accrued data was performed using the SPSS 21.0 software package and a P-value <0.05 calculated by t-Test, was considered significant. Results: Among 43 nurses included in the study, 14 (32.6%) were very comfortable taking care of tracheostomized patients, 13 (30.2%) were comfortable, and 16 (37.2%) were uncomfortable. Regarding knowledge, three main aspects of tracheostomy care were correctly answered (%) by all the nurses: knowledge of routine tracheal care (55%), tracheal care skills (11.6%), and tracheal emergency care (2.3%). The study showed a significant positive correlation between nurses' comfort level with tracheal care and academic degree, duration of pediatric experience, completion of more than one life support course, and attendance at the annual local tracheostomy care competency learning program (TCCLP; all P <0.05). Conclusion: Deficits exist in nurses' knowledge of tracheostomy care. Improved knowledge garnered through repetitive participation in tracheostomy competency programs and life support courses correlate with greater comfort and more than 5 years of pediatric experience. Nurses' deficits in emergency care knowledge and skills should be addressed through a structured educational program and a simulation, hands-on based TCCLP course, irrespective of comfort level with tracheostomy care.

Use of thrombolytic agents to treat neonatal thrombosis in clinical practice.

Among children, neonates have the highest incidence of thrombosis. Thrombolytic agents are used for the management of life and/or organ-threatening thrombosis. Literature on the efficacy and safety of thrombolytic agents in neonates is limited. We reviewed the evidence on dosing, administration, monitoring and treatment duration of tissue plasminogen activator (tPA), streptokinase and urokinase (URK) in neonates (≤ 28days). A systematic literature search was conducted of current databases from inception until 31 March 2021. The initial search yielded 6881 articles and 18 were retained for review. tPA, streptokinase and URK was utilized in 12, seven and four studies on 115, 51 and 16 patients, respectively. The dose range for tPA, streptokinase and URK was 0.01 -0.6 mg/kg/h, 50-2000 and 1000-0 000 units/kg/h, respectively, and treatment duration ranged from 30 min to 30 days. This is the first study to objectively summarize the efficacy and safety of thrombolytic agents in neonates. Overall, thrombolysis was associated with 87.9% complete or partial thrombus resolution and 7.4% recurrence risk. The bleeding risk associated with thrombolytic agents was 23.1% on pooled analysis, which is higher than other anticoagulants. Larger prospective studies are required to determine effective dosing regimens of these therapeutic drugs and further clarify their efficacy and safety. Blood Coagul Fibrinolysis 33:000-000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Risk factors for neonatal thrombosis: A retrospective study conducted in a single Canadian intensive care unit.

Among children, neonates have the highest incidence of thrombosis. We conducted a retrospective review of neonatal thrombosis, in a single intensive care unit (ICU) over 4.5 years. Among 4860 ICU admissions to our center, identified through the Canadian Neonatal Network database, 186 were associated with arterial and venous thrombosis involving 195 thrombotic sites. The neonatal thrombosis incidence was 38 per 1000 neonatal ICU admissions. We assessed patient characteristics and compared the association between risk factors and thrombosis. In the multivariate analysis, central venous catheters, sepsis, and respiratory distress syndrome were significant predictors of neonatal thrombosis.

Epidemiology, diagnosis and management of neonatal thrombosis: a single-center cohort study.

The incidence of neonatal venous and arterial thrombosis ranges from 6.9 to 15/1000 neonatal ICU (NICU) admissions, and is likely an underestimate based on population demographics, frequency of surveillance and vascular catheterization. This retrospective study involving 234 infants reviewed the epidemiology, diagnosis, and management of neonatal thrombosis in a single, tertiary care institution over more than 10 years. The incidence of thrombosis was 25/1000 NICU admissions, with a preterm to term infant ratio of 1.5 : 1 and a slightly higher proportion of male sex (55.1%). The mean (range) gestational age and birth weight was 33.8 weeks (23-41.6) and 2360 g (512-5890). The median age (IQR) of thrombus diagnosis was 7 (3-17) days. Portal vein thrombosis was most prevalent (59.4%) compared with other sites of thrombosis. Almost three-quarter (171/234; 73.1%) of the thrombotic episodes were line-related, while infection and surgery were associated with 19.7% (46/234) and 10.7% (25/234), respectively. Twenty patients (8.3%) were screened for thrombophilia and 3 were positive; 2 for antithrombin deficiency, 1 for factor V Leiden gene mutation. Subjects were followed with imaging for 3 months with a treatment duration, mean (IQR) of 33.5 (10.8-42.5) days. Complete clot resolution was significantly higher in the anticoagulation group (48%; 17%; P = 0.03) compared with untreated patients. No group difference was noted for partial thrombus resolution (33.3%; 12.4%; P = 0.313). Anticoagulation halted thrombus progression (2.6 versus 12.4%; P = 0.025) and fewer treated patients failed to attend follow-up visits (6.5 versus 18.6%; P = 0.022). Well designed, multicenter prospective studies with larger sample sizes are required to confirm these findings.

Comparison of the Canadian vs. the international risk scoring tool for respiratory syncytial virus prophylaxis in moderate-to-late preterm infants.

Aim: The study objective was to compare the Pediatric Investigators Collaborative Network on Infections in Canada risk scoring tool (CRST) that determines need for respiratory syncytial virus (RSV) prophylaxis in infants 33-35 weeks gestational age during the RSV season, with the newly developed international risk scoring tool (IRST). Methods: Children 33-35 weeks gestational age born during the 2018-2021 RSV seasons were prospectively identified following birth and scored with the validated CRST and IRST, that comprises seven and three variables respectively, into low- moderate- and high-risk groups that predict RSV-related hospitalization. Correlations between total scores on the two tools, and cut-off scores for the low-, moderate- and high-risk categories were conducted using the Spearman rank correlation. Results: Over a period of 3 RSV seasons, 556 infants were scored. Total risk scores on the CRST and the IRST were moderately correlated (rs = 0.64, p < 0.001). A significant relationship between the risk category rank on the CRST and the risk category rank on the IRST (rs = 0.53; p < 0.001) was found. The proportion of infants categorized as moderate risk for RSV hospitalization by the CRST and IRST were 19.6% (n = 109) and 28.1% (n = 156), respectively. Conclusion: The IRST may provide a time-efficient scoring alternative to the CRST with three vs. seven variables, and it selects a larger number of infants who are at moderate risk for RSV hospitalization for prophylaxis. A cost-utility analysis is necessary to justify country-specific use of the IRST, while in Canada a cost comparison is necessary between the IRST vs. the currently approved CRST prior to adoption.

Indications and outcomes of neonatal intubation: A single-center, prospective study in a middle-income country.

BACKGROUND: This study assessed the success rate and associated complications of hospital-wide neonatal endotracheal intubations by pediatric residents and neonatal fellows using direct laryngoscopy. Secondary objectives were to identify characteristics and indications for the procedure in a tertiary-care center. METHODS: A cross-sectional observational study was conducted. We prospectively collected performance and infant outcome data after neonatal intubation between March 1, 2019 and February 29, 2020. RESULTS: 171 intubations were observed in 105 infants. The median infant gestational age was 31.0 weeks (interquartile range [IQR]: 27.5-36.0 weeks). Fifty infants (48%) were very low birth weight (VLBW, <1500 g; median 1640 g [IQR: 870-2420 g]). The most common indication for intubation was respiratory failure (65%). Pediatric residents and neonatal fellows had overall success rates of 66% and 98%, respectively. The success rate for the first intubation attempt was higher with more advanced pediatric residency training (P < 0.001). The median attempts for each intubation were 1 (IQR: 1-2) for both VLBW and non-VLBW infants (P = 0.48). The adverse outcome rates were 5% and 3% for VLBW and non-VLBW infants, respectively (P = 0.53). More than 2 intubation attempts was the only significant independent risk factor for adverse outcomes (adjusted odds ratio 6.7; 95% CI 1.3-33.6; P = 0.02). CONCLUSIONS: The success rate of pediatric residents for neonatal intubation was similar for VLBW and non-VLBW infants. The main indication was respiratory failure, and nearly half were infants with VLBW. To minimize adverse sequelae, written guidelines limiting the number of intubation attempts by junior trainees are warranted.