Identification and Evaluation of Controlled Trials in Pediatric Cardiology: Crowdsourced Scoping Review and Creation of Accessible Searchable Database.

Cardiac disease in children is associated with significant morbidity and mortality as well as increased health resource utilisation. There is a perception that there is a paucity of high-quality studies, particularly randomized controlled trials (RCTs), in the field of pediatric cardiology. We sought to identify, examine, and map the range of RCTs conducted in children with cardiac conditions, including the development of a searchable open-access database. A literature search was conducted encompassing MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to 2018. All English-language RCTs enrolling children (age 0-21 years) with cardiac conditions were included. Data extraction and risk of bias assessments were performed in duplicate via crowdsourcing for each eligible study and entered into an online database. A total of 933 RCTs met eligibility criteria. Median trial recruitment was 49 patients (interquartile range 30-86) with 18.9% of studies (n = 176) including > 100 patients. A wide variety of populations and interventions were encompassed with congenital heart disease (79.8% of RCTs) and medications (63.3% of RCTs) often studied. Just over one-half of the trials (53.4%) clearly identified a primary outcome, and fewer than half (46.6%) fully documented a robust randomization process. Trials were summarised in a searchable online database (https://pediatrics.knack.com/cardiology-rct-database#cardiology-rcts/). Contrary to a commonly held perception, there are nearly 1,000 published RCTs in pediatric cardiology. The open-access database created as part of this project provides a resource that facilitates an efficient comprehensive review of the literature for clinicians and researchers caring for children with cardiac issues.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.