Prenatal Exposure to Valproic Acid Across Various Indications for Use.

Importance: Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy. Objectives: To determine pregnancy rates during valproic acid use and concomitant contraception use across indications. Design, Setting, and Participants: This retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days' supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023. Main Outcomes and Measures: Treatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined. Results: The cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]). Conclusions and Relevance: In this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.

Chronic Medication Use and Factors Associated With Polypharmacy Among Outpatient Pediatric Patients.

OBJECTIVE: This study aimed to determine the prevalence and predictors of chronic polypharmacy among pediatric patients in an outpatient setting. METHODS: We conducted a review of medications dispensed to patients from an outpatient pediatric facility during a 12-month period. Patients who received chronic medications (≥30 days' supply), which contained at least 1 active pharmaceutical ingredient were included in the study. Descriptive analysis was used to determine prevalence of polypharmacy while predictive factors for polypharmacy were evaluated using logistic regression. RESULTS: Our study included 3920 patients (median age, 9.9 years; IQR, 9.4) and 16,401 medications. The median number of chronic medications used among our study cohort was 2.0 (IQR, 1) with polypharmacy identified in 309 (7.9%) patients. Predictors for polypharmacy were age and the use of certain therapeutic class of medications. Patients 12 to <19 years old (OR, 6.95; 95% CI, 4.1-10.1) were more likely to require ≥5 concurrent medications compared with patients younger than 2 years of age. Use of calcium supplements (OR, 21.2; 95% CI, 11.3-39.6), Vitamin D analogues (OR, 14.3; 95% CI, 8.0-25.8), and systemic glucocorticoids (OR, 18.8; 95% CI, 10.7-33.2) were also highly associated with polypharmacy. CONCLUSIONS: Adolescents and children with chronic medical conditions who require prolonged systemic glucocorticoids, calcium, and Vitamin D supplements are at higher risk of incurring long-term polypharmacy. This subgroup of pediatric patients may be more vulnerable to the occurrence of negative outcomes resulting from the use of multiple chronic medications.

Use of complementary or alternative medicine and potential interactions with chronic medications among Chinese survivors of childhood cancer.

PURPOSE: This study explored the pattern of complementary or alternative medicine (CAM) use among Chinese survivors of childhood cancer and identified potential drug-CAM interactions and factors predicting CAM use. METHODS: This cross-sectional study recruited 393 survivors of childhood cancer (male, 57.8%; mean age, 17.7 [SD = 7.3] years; mean years post-treatment, 8.8 [SD = 5.0]) from a public hospital in Hong Kong. Participants reported CAM and over-the-counter medications that they used in the past year. Prescription drug data were extracted from pharmacy dispensing records. Potential interactions between concurrent CAM and chronic medications were identified from well-established CAM-drug/herb-drug interaction databases. A multivariate logistic regression was performed to analyze associations of socio-demographic and clinical factors with CAM use. RESULTS: Half (n = 205/393, 52.2%) of the participants reported the use of CAM. The most popular CAMs were traditional Chinese medicine (n = 127/205, 62.0%) and natural products (n = 114/205, 55.3%). Among the 69 survivors (33.7%) concurrently using CAM and chronic medications, one-third (n = 21/69, 30.4%) were at risk of drug-CAM interactions that are of moderate significance. Adult survivors were more likely to use CAM than pediatric survivors (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.31-4.41). Brain tumor survivors were more likely than other solid tumor survivors to use non-oral therapies (OR, 2.70; 95% CI, 1.01-7.72). CONCLUSIONS: The prevalence of CAM use among Chinese survivors of childhood cancer was high. A minority of survivors had a risk of clinically significant CAM-drug interactions. Future studies should focus on survivors' behavior and motivations for CAM use. IMPLICATIONS FOR CANCER SURVIVORS: As the concurrent use of CAM and chronic medications might result in interactions, healthcare providers should proactively identify such interactions and develop referral pathways to promote evidence-based integrative therapies for survivors.

Use of Chronic Prescription Medications and Prevalence of Polypharmacy in Survivors of Childhood Cancer.

BACKGROUND: As survivors of childhood cancer age, development of cancer treatment-related chronic health conditions often occur. This study aimed to describe the pattern of chronic prescription medication use and identify factors associated with polypharmacy among survivors of childhood cancer. METHODS: This was a retrospective study conducted at the pediatric oncology long-term follow-up clinic in Hong Kong. Eligible subjects included survivors who were (1) diagnosed with cancer before 18 years old, (2) were at least 3 years post-cancer diagnosis and had completed treatment for at least 30 days, and (3) receiving long-term follow-up care at the study site between 2015 and 2018. Dispensing records of eligible survivors were reviewed to identify medications taken daily for ≥30 days or used on an "as needed" basis for ≥6 months cumulatively within the past 12-month period. Polypharmacy was defined as the concurrent use of ≥5 chronic medications. Multivariable log-binomial modeling was conducted to identify treatment and clinical factors associated with medication use pattern and polypharmacy. RESULTS: This study included 625 survivors (mean current age = 17.9 years, standard deviation [SD] = 7.2 years) who were 9.2 [5.2] years post-treatment. Approximately one-third (n = 219, 35.0%) of survivors were prescribed at least one chronic medication. Frequently prescribed medication classes include systemic antihistamines (26.5%), sex hormones (19.2%), and thyroid replacement therapy (16.0%). Overall prevalence of polypharmacy was 5.3% (n = 33). A higher rate of polypharmacy was found in survivors of CNS tumors (13.6%) than in survivors of hematological malignancies (4.3%) and other solid tumors (5.3%) (P = .0051). Higher medication burden was also observed in survivors who had undergone cranial radiation (RR = 6.31; 95% CI = 2.75-14.49) or hematopoietic stem-cell transplantation (HSCT) (RR = 3.53; 95% CI = 1.59-7.83). CONCLUSION: Although polypharmacy was observed in a minority of included survivors of childhood cancer, chronic medication use was common. Special attention should be paid to survivors of CNS tumors and survivors who have undergone HSCT or cranial radiation. These individuals should be monitored closely for drug-drug interactions and adverse health outcomes that may result from multiple chronic medications, particularly during hospitalization in an acute care setting.

Influenza vaccine coverage and predictive factors associated with influenza vaccine uptake among pediatric patients.

BACKGROUND: Despite recommendations from health care authorities, reports of severe influenza occur yearly among unvaccinated infants and children. OBJECTIVES: This study investigated influenza vaccine coverage and predictive factors for vaccination status among pediatric patients during the 2016-2017 winter influenza season. METHODS: A cross-sectional survey was conducted among parents of our study population identified through a major pediatric outpatient clinic in Hong Kong. Parents with a child aged 6 months to 17 years were invited to complete a questionnaire that assessed the current influenza vaccine status of the child and the parents' understanding and beliefs regarding influenza and its vaccine. A backward logistic regression was conducted to determine predictive factors and adjusted odds ratios associated with influenza vaccine uptake. RESULTS: Our study included 348 parents and 405 pediatric patients. Of these, 142 pediatric patients (35.1%) received full vaccination. Predictive factors associated with the child's positive influenza vaccine status include a "very good" parental understanding of influenza and its vaccine (adjusted odds ratio, 6.7; 95% confidence interval, 2.1-21.5), a child with chronic medical condition and a "high" cue to action (adjusted odds ratio, 5.7; 95% confidence interval, 2.8-11.6), and a "high" perceived susceptibility toward influenza (adjusted odds ratio, 4.8; 95% confidence interval, 2.1-10.8). CONCLUSIONS: This study reflects the low influenza vaccine coverage among pediatric patients. Interventions focusing on parental knowledge and understanding of influenza and its vaccine may improve future vaccine uptake among the pediatric population.

Occurrence of Potential Adverse Drug Events from Prescribing Errors in a Pediatric Intensive and High Dependency Unit in Hong Kong: An Observational Study.

BACKGROUND: Critically ill pediatric patients are considered at high risk for medication errors. Although much research focuses on the actual errors, equally important are medication errors that, although intercepted, carried the potential for an adverse drug event. The aim of this study was to determine the occurrence of prescribing errors and potential adverse drug events (pADEs) in a local pediatric intensive and critical care unit (PICU) in Hong Kong. Our secondary objective was to determine the type of error, nature of medication involved and the time of error occurrence. METHODS: We conducted a prospective observational chart review among patients in a pediatric intensive and high dependency unit between January 16, 2015 and April 20, 2015. Medical charts for each patient were reviewed for the occurrence of a prescribing error or pADE. Each pADE was assessed for the type of error, the classification of agent involved, clinical severity of the error, and the time the error occurred. RESULTS: Forty-one patients with a mean age of 3.2 years were included in our study. Of these patients, 19 (46.3%) experienced at least one pADE. We identified 131 pADEs, 129 of which were prescribing errors conferring a rate of 6.8 errors per affected patient or 3.1 errors per patient admitted to the PICU. The most common error found in the study was incorrect dose calculation (48.1%), with intravenous fluids (41.7%), cardiovascular agents (15.0%), and anti-infectives (12.5%) the most common agents involved with an error. The majority of the pADEs in our study were either clinically serious (33.1%) or significant (44.9%) in nature. Nearly one in every four errors required monitoring and/or intervention to prevent harm, and almost all (96.9%) of the prescribing errors were intercepted before reaching the patient. CONCLUSION: This study highlights incorrect dose calculation as the most common prescribing error in a pediatric critical care setting. Intravenous fluids, cardiovascular agents, and anti-infectives were the classes of medication most commonly involved with a pADE. Due to the high-risk nature of medications used and the critical condition of these patients, more than three-quarters of pADEs were considered to be clinically serious or significant in causing patient harm.