BACKGROUND: The lack of specific medicines and labeling recommendations for the pediatric population is a long-standing problem. Using data from an observational study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that off-label status is a risk factor for ADRs. METHODS: A prospective intensive surveillance was conducted at a pediatric ward of a public teaching hospital. Adverse events to labeled and off-label use were assessed for incidence, severity and predictors. A multivariate Cox proportional hazards regression model used to assess off-label use is a risk factor for ADR occurring. RESULTS: Off-label and labeled use were responsible for 34 (67%) and 17 (33%) ADRs respectively. Medicines which lacked complete pediatric labeling had the greatest odds for ADRs (9.21% of medicines in this category were implicated, OR 2.84 (95% CI 1.37-7.09). Number of off-label medicines given to patient significantly increased the hazard of an ADR (hazard ratio (HR) 1.28, 95% CI 0.43-3.78, P = 0.002). Number of medicines given also significantly increased the hazard (HR 1.2, 95% CI 0.80-1.71, P < 0.001). CONCLUSIONS: Use of off-label medicines were more likely to be implicated in an ADR than labeled medicines. This off-label use would be acceptable if evidence of potential benefits outweighs ADRs risk.

Background:The optimal intravenous device for antibiotic administration for children with respiratory disease is uncertain. We assessed the feasibility of a randomized controlled trial comparing midline catheters with peripherally inserted central catheters.Methods: Prospective, two-arm, feasibility randomized controlled trial in an Australian tertiary, pediatric hospital. Random assignment of 110 children (<18 years) to receive (i) midline catheter and (ii) peripherally inserted central catheters. Primary outcome was feasibility (eligibility, recruitment, retention, protocol adherence, and acceptability), and the primary clinical outcome was general anesthesia requirement for intravenous catheter insertion. Secondary outcomes: insertion time, treatment delays, infusion efficiency, device failure, complications, and cost.Results: There was 80% recruitment, 100% retention, no missing data, and high patient/ staff acceptability. Mean patient experience assessed on a 0-10 numeric rating scale was 8.0 peripherally inserted central catheters and 9.0 (midline catheters), respectively. Participant eligibility was not achieved (49% of screened patients) and moderate protocoladherence across groups (89% peripherally inserted central catheters vs. 76% midline catheter). Insertion of midline catheter for pulmonary optimization reduced the requirement for general anesthesia compared to peripherally inserted central catheters (10% vs. 69%; odds ratio = 0.01, 95% confidence interval: 0.00-0.09). Midline catheters failed more frequently (18.1 vs. 5.5 peripherally inserted central catheters per 1000 catheter-days); however, this reduced over trial duration. Midline catheter insertion compared to peripherally inserted central catheters saved AUD$1451 per pulmonary optimization episode.Conclusions: An efficacy trial is feasible with expanded eligibility criteria and intensive staff training when introducing a new device. Midline catheter for peripherally compatible infusions is acceptable to patients and staff, might negate the need for general anesthesia and results in significant cost savings.

Background. In the absence of standard pediatric prescribing information, clinicians often use medicines in an off-label way. Many studies have been published across the globe reporting different rates of off-label use. There is currently no study based on Indian drug formulary. Methods. The prospective observational study included pediatric patients in ages between 0 and 12 years admitted in a tertiary care hospital. Off-label use was assessed using the National Formulary of India (NFI). Predictors of off-label use were determined by logistic regression. Results. Of the 1645 medications prescribed, 1152 (70%) were off-label based on 14 possible off-label categories. Off-label medicines were mainly due to dose difference and use in restricted age limits as indicated in NFI. Respiratory medicines (82%), anti-infectives (73%), and nervous system medicines (53%) had higher off-label use. Important predictors of off-label prescribing were pediatric patients in age of 0 to 2 years (OR 1.68, 95% CI; P < 0.001) and hospital stay of six to 10 days (OR 1.91, 95% CI; P < 0.001). Conclusion. Off-label prescribing is common among pediatric patients. There is need to generate more quality data on the safety and efficacy of off-label medicines to rationalize pediatric pharmacotherapy.

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.