Weaning Dexmedetomidine in Non-ICU Areas: An Implementation Effort.

OBJECTIVES: To develop and implement clinical practice guidelines for safely weaning dexmedetomidine infusions in non-ICU areas. DESIGN: Development, implementation, and analysis of effectiveness of clinical practice guidelines. SETTING: Quaternary care academic free-standing pediatric hospital. PATIENTS: Children, otherwise medically ready for transfer to non-ICU areas, who were undergoing a planned wean of a dexmedetomidine infusion. INTERVENTIONS: Subject matter experts developed evidence-based guidelines for weaning dexmedetomidine in patients whose critical phase of illness had resolved. MEASUREMENTS AND MAIN RESULTS: Searches identified no prospective studies of dexmedetomidine weaning. We identified two retrospective reviews of withdrawal symptoms and one on the use of clonidine. There were case studies on withdrawal symptoms. Guidelines were piloted on a cohort of 24 patients while in the ICU. The guidelines were then implemented in non-ICU areas for patients undergoing dexmedetomidine weaning after ICU transfer. Over a 2-year period (October 1, 2018, to September 30, 2020), 63 patients (1 mo to 18 yr old) successfully weaned dexmedetomidine in non-ICU areas. The median time to discontinuation of dexmedetomidine after transfer to non-ICU areas was 5.8 days (interquartile range, 4.75-15 d). Fifty-eight percent (n = 41) of all patients were considered high risk for dexmedetomidine withdrawal based on the dose, duration of exposure, and the risk of experiencing physiologic detriment with more than mild withdrawal. Twenty-nine patients (46%) exhibited no signs or symptoms of withdrawal while weaning per guidelines. For those with signs and symptoms of withdrawal, the most common were tachycardia (n = 26, 40%), agitation (n = 9, 14%), and hypertension (n = 9, 11%). CONCLUSIONS: Weaning dexmedetomidine in non-ICU areas is feasible and can be accomplished safely even among pediatric patients at high risk for withdrawal using standardized weaning guidelines. At our institution, implementation was associated with reduced ICU length of stay for patients recovering from critical illness.

Patients dispensed medications with actionable pharmacogenomic biomarkers: rates and characteristics.

PURPOSE: Pharmacogenomic biomarkers are increasingly listed on medication labels and authoritative guidelines but pharmacogenomic-guided prescribing is not yet common. Our objective was to assess the potential for incorporating knowledge of patients' genomic characteristics into prescribing practices. METHODS: We performed a retrospective analysis of claims data for 2,096,971 beneficiaries with pharmacy coverage from a national, commercial health insurance plan between January 2017 and December 2019. Children between 0 and 17 years comprised 21% of the cohort. Adults were age 18 to 64. Medications with actionable pharmacogenomic biomarkers (MAPBs) were identified using public information from the US Food and Drug Administration (FDA), Clinical Pharmacogenomics Implementation Consortium (CPIC), and PharmGKB. RESULTS: MAPBs were dispensed to 63% of the adults and 29% of the children in the cohort. Most frequently dispensed were ibuprofen, ondansetron, codeine, and oxycodone. Most common were medications with CYP2D6, G6PD, or CYPC19 pharmacogenomic biomarkers. Ten percent of the cohort were codispensed more than one MAPB for at least 30 days. CONCLUSION: The number of people who might benefit from pharmacogenomic-guided prescribing is substantial. Future work should address obstacles to integrating genomic data into prescriber workflows, complex factors contributing to the magnitude of benefit, and the clinical availability of reliable on-demand or pre-emptive pharmacogenomic testing.

Adverse drug event presentation and tracking (ADEPT): semiautomated, high throughput pharmacovigilance using real-world data.

OBJECTIVE: To advance use of real-world data (RWD) for pharmacovigilance, we sought to integrate a high-sensitivity natural language processing (NLP) pipeline for detecting potential adverse drug events (ADEs) with easily interpretable output for high-efficiency human review and adjudication of true ADEs. MATERIALS AND METHODS: The adverse drug event presentation and tracking (ADEPT) system employs an open source NLP pipeline to identify in clinical notes mentions of medications and signs and symptoms potentially indicative of ADEs. ADEPT presents the output to human reviewers by highlighting these drug-event pairs within the context of the clinical note. To measure incidence of seizures associated with sildenafil, we applied ADEPT to 149 029 notes for 982 patients with pediatric pulmonary hypertension. RESULTS: Of 416 patients identified as taking sildenafil, NLP found 72 [17%, 95% confidence interval (CI) 14-21] with seizures as a potential ADE. Upon human review and adjudication, only 4 (0.96%, 95% CI 0.37-2.4) patients with seizures were determined to have true ADEs. Reviewers using ADEPT required a median of 89 s (interquartile range 57-142 s) per patient to review potential ADEs. DISCUSSION: ADEPT combines high throughput NLP to increase sensitivity of ADE detection and human review, to increase specificity by differentiating true ADEs from signs and symptoms related to comorbidities, effects of other medications, or other confounders. CONCLUSION: ADEPT is a promising tool for creating gold standard, patient-level labels for advancing NLP-based pharmacovigilance. ADEPT is a potentially time savings platform for computer-assisted pharmacovigilance based on RWD.

Adverse drug event rates in pediatric pulmonary hypertension: a comparison of real-world data sources.

OBJECTIVE: Real-world data (RWD) are increasingly used for pharmacoepidemiology and regulatory innovation. Our objective was to compare adverse drug event (ADE) rates determined from two RWD sources, electronic health records and administrative claims data, among children treated with drugs for pulmonary hypertension. MATERIALS AND METHODS: Textual mentions of medications and signs/symptoms that may represent ADEs were identified in clinical notes using natural language processing. Diagnostic codes for the same signs/symptoms were identified in our electronic data warehouse for the patients with textual evidence of taking pulmonary hypertension-targeted drugs. We compared rates of ADEs identified in clinical notes to those identified from diagnostic code data. In addition, we compared putative ADE rates from clinical notes to those from a healthcare claims dataset from a large, national insurer. RESULTS: Analysis of clinical notes identified up to 7-fold higher ADE rates than those ascertained from diagnostic codes. However, certain ADEs (eg, hearing loss) were more often identified in diagnostic code data. Similar results were found when ADE rates ascertained from clinical notes and national claims data were compared. DISCUSSION: While administrative claims and clinical notes are both increasingly used for RWD-based pharmacovigilance, ADE rates substantially differ depending on data source. CONCLUSION: Pharmacovigilance based on RWD may lead to discrepant results depending on the data source analyzed. Further work is needed to confirm the validity of identified ADEs, to distinguish them from disease effects, and to understand tradeoffs in sensitivity and specificity between data sources.

Initial Pain Management in Pediatric Acute Pancreatitis: Opioid Versus Non-opioid.

Nearly all patients with acute pancreatitis (AP) experience some degree of abdominal pain that is severe enough to prompt medical evaluation and necessitate analgesia. Effective analgesia is a priority in caring for such patients. Despite its importance, strategies for pain management in AP have been poorly studied, particularly in the field of pediatrics. Presently, no published data examine the management of pain because of AP in children at the time of initial presentation. Management approaches are often extrapolated from adult practice and based on anecdotal experience in the absence of objective data. The aim of our study was to examine the initial provision of analgesia to children who presented to a pediatric emergency department with AP.

Creating a scalable clinical pharmacogenomics service with automated interpretation and medical record result integration - experience from a pediatric tertiary care facility.

OBJECTIVE: This paper outlines the implementation of a comprehensive clinical pharmacogenomics (PGx) service within a pediatric teaching hospital and the integration of clinical decision support in the electronic health record (EHR). MATERIALS AND METHODS: An approach to clinical decision support for medication ordering and dispensing driven by documented PGx variant status in an EHR is described. A web-based platform was created to automatically generate a clinical report from either raw assay results or specified diplotypes, able to parse and combine haplotypes into an interpretation for each individual and compared to the reference lab call for accuracy. RESULTS: Clinical decision support rules built within an EHR provided guidance to providers for 31 patients (100%) who had actionable PGx variants and were written for interacting medications. A breakdown of the PGx alerts by practitioner service, and alert response for the initial cohort of patients tested is described. In 90% (355/394) of the cases, thiopurine methyltranferase genotyping was ordered pre-emptively. DISCUSSION: This paper outlines one approach to implementing a clinical PGx service in a pediatric teaching hospital that cares for a heterogeneous patient population. There is a focus on incorporation of PGx clinical decision support rules and a program to standardize report text within the electronic health record with subsequent exploration of clinician behavior in response to the alerts. CONCLUSION: The incorporation of PGx data at the time of prescribing and dispensing, if done correctly, has the potential to impact the incidence of adverse drug events, a significant cause of morbidity and mortality.

Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department.

STUDY OBJECTIVE: Assessment of preprocedural fasting is considered essential in minimizing the risks of procedural sedation and analgesia. Established fasting guidelines are difficult to follow in the emergency department (ED). We characterize the fasting status of patients receiving procedural sedation and analgesia in a pediatric ED and assess the relationship between fasting status and adverse events. METHODS: A prospective case series was conducted in a children's hospital ED during an 11-month period. All consecutive patients requiring procedural sedation and analgesia were included. Preprocedural fasting state and adverse events were recorded. The percentage of patients undergoing procedural sedation and analgesia who did not meet fasting guidelines was determined. Adverse events were analyzed in relation to fasting status. RESULTS: One thousand fourteen patients underwent procedural sedation and analgesia, and data on fasting status were available for 905 (89%) patients. Of these 905 patients, 509 (56%; 95% confidence interval [CI] 53% to 60%) did not meet fasting guidelines. Seventy-seven adverse events occurred in 68 (6.7%; 95% CI 5.2% to 8.4%) of the 1,014 patients. All adverse events were minor and successfully treated. Adverse events occurred in 32 (8.1%; 95% CI 5.6% to 11.2%) of 396 patients who met and 35 (6.9%; 95% CI 4.8% to 9.4%) of 509 patients who did not meet fasting guidelines. There was no significant difference in median fasting duration between patients with and without adverse events and between patients with and without emesis. Emesis occurred in 15 (1.5%) patients. There were no episodes of aspiration (1-sided 97.5% CI 0% to 0.4%). CONCLUSION: Fifty-six percent of children undergoing ED procedural sedation and analgesia were not fasted in accordance with established guidelines. There was no association between preprocedural fasting state and adverse events.