Central venous access device adverse events in pediatric patients with cancer: a systematic review and meta-analysis.

PURPOSE: To systematically review the proportion and incidence of CVAD-associated complications in pediatric patients with cancer. METHODS: PubMed, Embase, and the Cumulative Index of Nursing and Allied Health Literature were searched from 2012 to 2022. Cohort studies and the control arm of randomized controlled trials, which reported CVAD-associated complications in pediatric patients aged 0-18 years, were included. CVAD complications were defined as CVAD failure, central line-associated bloodstream infection (CLABSI), local infection, occlusion, CVAD-associated venous thromboembolism, dislodgement/migration, breakage/rupture, and dehiscence. The pooled proportion and incidence rate (IR) for each CVAD-associated complication were reported. RESULTS: Of 40 included studies, there was mixed quality of methods and reporting. Approximately 31.4% (95% confidence interval [CI] 22.5-41.1; 6920 devices) of devices experienced a CVAD-associated complication, and 14.8% (95% CI 10.2-20.1; 24 studies; 11,762 devices) of CVADs failed before treatment completion (incidence rate (IR) of 0.5 per 1000 catheter days (95% CI 0.3-0.8; 12 studies; 798,000 catheter days)). Overall, 21.2% (95% CI 14.3-28.9; 26 studies; 5054 devices) of CVADs developed a CLABSI, with an IR of 0.9 per 1000 catheter days (95% CI 0.6-1.3; 12 studies; 798,094 catheter days). Tunneled central venous catheters (TCVC) and peripherally inserted central catheters (PICCs) were associated with increased complications in comparison to totally implanted venous access devices (TIVADs). CONCLUSION: CVAD complication rates in this population remain high. TCVCs and PICCs are associated with increased complications relative to TIVADs. Insufficient evidence exists to guide device selection in this cohort, necessitating further research to determine the role of PICCs in pediatric cancer care. PROSPERO: CRD42022359467. Date of registration: 22 September 2022.

Association of antenatal and early childhood air pollution and greenspace exposures with respiratory pathogen upper airway acquisitions and respiratory health outcomes.

The association of air pollution and greenspace with respiratory pathogen acquisition and respiratory health was investigated in a community-based birth-cohort of 158 Australian children. Weekly nasal swabs and daily symptom-diaries were collected for 2-years, with annual reviews from ages 3-7-years. Annual exposure to fine-particulate-matter (PM2.5), nitrogen-dioxide (NO2), and normalised-difference-vegetation-index (NDVI) was estimated for pregnancy and the first 2-years-of-life. We examined rhinovirus, any respiratory virus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae detections in the first 3-months-of-life, age at initial pathogen detection, wheezing in the first 2-years, and asthma at ages 5-7-years. Our findings suggest that higher NDVI was associated with fewer viral and M. catarrhalis detections in the first 3-months, while increased PM2.5 and NO2 were linked to earlier symptomatic rhinovirus and H. influenzae detections, respectively. However, no associations were observed with wheezing or asthma. Early-life exposure to air pollution and greenspace may influence early-life respiratory pathogen acquisition and illness. .

Association of rhinovirus and potentially pathogenic bacterial detections in the first 3 months of life with subsequent wheezing in childhood.

OBJECTIVE: Airway interactions between viruses, especially rhinoviruses, and potentially pathogenic bacteria (PPB; Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in early infancy may increase the risk of subsequent wheezing and asthma. We evaluated the association between rhinovirus and PPB in the first 3 months of life and wheezing episodes before age 2 years and asthma at age 5-7 years. METHODS: An Australian community-based birth cohort of healthy children involved parents collecting nasal swabs weekly and completing symptom diaries daily until age 2 years. In a follow-up subset, asthma diagnosis was assessed annually until age 7 years. Swabs were analyzed by real-time polymerase chain reaction assays. Children were included if they returned symptom diaries beyond age 3 months (wheeze) or were reviewed at age 5-7 years (asthma). RESULTS: 1440 swabs were returned by 146 children in the first 3 months of life. Wheeze and asthma outcomes were recorded for 146 and 84 children, respectively. Each additional week of rhinovirus detection increased the incidence of wheezing before age 2 years by 1.16 times (95% confidence interval [CI]: 0.99-1.35). There were no significant associations between bacteria and wheeze. Each additional week with H. influenzae increased the odds of asthma at age 5-7 years by 135% (odds ratio: 2.35, 95% CI: 0.99-5.58). No significant interaction was observed between rhinovirus and PPB for wheezing or asthma. CONCLUSION: Early life rhinovirus infection was associated with wheezing before age 2 years and H. influenzae with asthma by age 5-7 years. Microbes may play an etiologic role in wheezing and asthma, warranting further study.

Interference between rhinovirus and other RNA respiratory viruses in the first 2-years of life: A longitudinal community-based birth cohort study.

BACKGROUND: Cross-sectional studies report negative associations between rhinovirus and other RNA respiratory viruses. However, longitudinal studies with frequent, serial sampling are needed to identify the directionality of this relationship and its nature. OBJECTIVE: To investigate the association between rhinovirus and other RNA respiratory viruses detected 1-week apart. METHODS: The Observational Research in Childhood Infectious Diseases cohort study was conducted in Brisbane, Australia (2010-2014). Parents collected nasal swabs weekly from birth until age 2-years. Swabs were analysed by real-time polymerase chain reaction. The association between new rhinovirus detections and five other RNA viruses (influenza, respiratory syncytial virus, parainfluenza viruses, seasonal human coronaviruses, and human metapneumovirus) in paired swabs 1-week apart were investigated. RESULTS: Overall, 157 children provided 8,101 swabs, from which 4,672 paired swabs 1-week apart were analysed. New rhinovirus detections were negatively associated with new pooled RNA respiratory virus detections 1-week later (adjusted odds ratio (aOR) 0.48; 95% confidence interval (CI): 0.13-0.83), as were pooled RNA virus detections with new rhinovirus detections the following week (aOR 0.34; 95%CI: 0.09-0.60). At the individual species level, rhinovirus had the strongest negative association with new seasonal human coronavirus detections in the subsequent week (aOR 0.34; 95%CI: 0.120.95) and respiratory syncytial virus had the strongest negative association with rhinovirus 1-week later (aOR 0.21; 95%CI: 0.050.88). CONCLUSION: A strong, negative bidirectional association was observed between rhinovirus and other RNA viruses in a longitudinal study of a community-based cohort of young Australian children. This suggests within-host interference between RNA respiratory viruses.

Pediatric central venous access devices: practice, performance, and costs.

BACKGROUND: Healthcare delivery is reliant on a functional central venous access device (CVAD), but the knowledge surrounding the burden of pediatric CVAD-associated harm is limited. METHODS: A prospective cohort study at a tertiary-referral pediatric hospital in Australia. Children <18 years undergoing insertion of a CVAD were screened from the operating theatre and intensive care unit records, then assessed bi-weekly for up to 3 months. Outcomes were CVAD failure and complications, and associated healthcare costs (cost of complications). RESULTS: 163 patients with 200 CVADs were recruited and followed for 6993 catheter days, with peripherally inserted central catheters most common (n = 119; 60%). CVAD failure occurred in 20% of devices (n = 30; 95% CI: 15-26), at an incidence rate (IR) of 5.72 per 1000 catheter days (95% CI: 4.09-7.78). CVAD complications were evident in 43% of all CVADs (n = 86; 95% CI: 36-50), at a rate of 12.29 per 1000 catheter days (95% CI: 9.84-15.16). CVAD failure costs were A$826 per episode, and A$165,372 per 1000 CVADs. Comparisons between current and recommended practice revealed inconsistent use of ultrasound guidance for insertion, sub-optimal tip-positioning, and appropriate device selection. CONCLUSIONS: CVAD complications and failures represent substantial burdens to children and healthcare. Future efforts need to focus on the inconsistent use of best practices. IMPACT: Current surveillance of central venous access device (CVAD) performance is likely under-estimating actual burden on pediatric patients and the healthcare system. CVAD failure due to complication was evident in 20% of CVADs. Costs associated with CVAD complications average at $2327 (AUD, 2020) per episode. Further investment in key diverse practice areas, including new CVAD types, CVAD pathology-based occlusion and dislodgment strategies, the appropriate use of device types, and tip-positioning technologies, will likely lead to extensive benefit.

Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life.

OBJECTIVE: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2 years of life, RSV-NA at 3 years, and respiratory health to age 5 years. METHODS: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord blood and at age 3 years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5 years and physician-diagnosed asthma at 5 years was collected by parent report. RESULTS: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio [aIRR] 0.63; 95% confidence interval [CI]: 0.40-1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95% CI: 0.25-1.02) of RSV acute lower respiratory infections (ALRI) at 12-24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95% CI: 0.99-1.69), wheeze-associated ALRI (aIRR 1.75; 95% CI: 1.08-2.82), and severe ALRI (aIRR 2.76; 95% CI: 1.63-4.70) at age 6-<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3 years, or wheeze or asthma at 5 years. CONCLUSIONS: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5 years of life. Additional strategies to control RSV-related illness in childhood are needed.

Epidemiology of respiratory syncytial virus in a community birth cohort of infants in the first 2 years of life.

Respiratory syncytial virus (RSV) is the most common virus identified in children hospitalised with acute respiratory infections. However, less is known about RSV in community settings. This report describes RSV epidemiology in the community, including acute illness episodes, healthcare burden, and risk factors in Australian children during the first 2-years of life. A community-based, birth cohort from Brisbane, Australia, followed children until their second birthday. Parents completed daily respiratory symptom and illness-burden diaries. Weekly parent-collected nasal swabs were analysed for RSV by real-time polymerase chain reaction assays. Serum RSV-neutralising antibodies were assayed at age 3 years. Overall, 158 children provided 11,216 swabs, of which 104 were RSV-positive (85 incident episodes). RSV incidence in the first 2 years of life was 0.46 (95% CI = 0.37-0.58) episodes per child-year. Incidence increased with age and formal childcare attendance and was highest in autumn. Of 82 episodes linked with symptom data, 60 (73.2%) were symptomatic, 28 (34.1%) received community-based medical care, and 2 (2.4%) led to hospitalisation. Viral load was higher in symptomatic than asymptomatic infections. In 72 children, RSV-specific antibody seroprevalence was 94.4% at age 3 years.Conclusion: RSV incidence increased after age 6-months with approximately three-quarters of infections symptomatic and most infections treated in the community. What is known •RSV is a major cause of hospitalisation for acute lower respiratory infections in infants and young children, especially in the first 6 months of life. •However, limited data exist on the overall burden in young children at the community level. What is new •RSV incidence in the community increases after age 6 months, and by 3 years, most children have been infected. •About one-quarter of RSV infections were asymptomatic in children aged < 2 years, and approximately 60% of children with RSV-related symptoms had a healthcare contact of any kind with most managed within the community.