A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

Antihypertensive utilization patterns among pregnant persons with pre-existing hypertension in the US: A population-based study.

BACKGROUND: Hypertension among persons with childbearing potential is on the rise. Maintaining proper blood pressure during pregnancy is vital to prevent maternal and neonatal complications. Yet, limited evidence on the risk-benefit of various antihypertensives presents challenges for informed decision-making during this critical period. This study aimed to examine the utilization patterns of different classes of antihypertensives among persons with pre-existing hypertension before, during, and after pregnancy. METHODS: We used MarketScan® Commercial Database 2011-2020 to analyze antihypertensive utilization among pregnant persons aged 12 to 55 identified via a validated algorithm. Pre-existing hypertension was defined as ≥1 inpatient or ≥2 outpatient encounters for hypertension within the 180 days preceding the LMP. Antihypertensive utilization was described during target periods: 0-3 months (0-3M) before pregnancy, 1st/2nd/3rd trimester (T1/2/3), 0-3M, and 4-6M after pregnancy. RESULTS: We identified 1,950,292 pregnancies, of which 20,576 (12,978 live and 7,598 non-live) had pre-existing hypertension. Both groups had similar antihypertensive use (80.1% and 81.0%, respectively) during the 6 months before pregnancy (baseline). For live-birth pregnancies, 13.9% of baseline users discontinued treatment during pregnancy, while 28.9% of non-users initiated antihypertensives during pregnancy, and 17.2% started postpartum. Before pregnancy, the predominant antihypertensives included thiazide diuretics (21.9%), combined α- and ß-blockers (18.4%), and dihydropyridines (16.2%). During pregnancy, thiazide diuretics, cardioselective ß-blockers, and ACE inhibitors declined (T3: 3.0%, 4.2%, and 0.8%). Dihydropyridine use was steady during pregnancy, but preference shifted from amlodipine to nifedipine in T3 (2.2.% vs.10.8%). Central α2-agonists increased during pregnancy (up to 15.2% in T3) compared to both pre- (9.8%) and post-pregnancy (5.7%). ARBs mirrored ACE inhibitors, with less than 1% utilization in later trimesters. Combination agents dropped from 10.8% pre-pregnancy to 0.8% in T3, then rebounded to 7.3% post-pregnancy. CONCLUSION: Research is warranted to evaluate the choice of antihypertensives and optimal timing to switch to safer alternatives, considering maternal and fetal outcomes.

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.

Prenatal Care Initiation and Exposure to Teratogenic Medications.

Importance: With new legal abortion restrictions, timing of prenatal care initiation is critical to allow for discussion of reproductive options among pregnancies exposed to teratogenic medications. Objective: To investigate the prevalence of prenatal exposure to teratogenic medications and prenatal care initiation across gestational weeks. Design, Setting, and Participants: This descriptive, population-based cross-sectional study used health encounter data from a national sample of individuals with employer-sponsored health insurance. A validated algorithm identified pregnancies among persons identifying as female that ended with a live or nonlive outcome between January 2017 and December 2019. Data were analyzed from December 2022 to December 2023. Exposures: Prenatal exposure to any of 137 teratogenic medications, measured via pharmacy and medical claims. Measurement of prenatal care initiation was adapted from the Children's Health Care Quality Measures. Main Outcomes and Measures: Prevalence of prenatal exposure to teratogens and prenatal care initiation by gestational week. Timing of prenatal teratogenic exposure was compared with timing of prenatal care initiation and legal abortion cutoffs. Results: Among 639 994 pregnancies, 472 472 (73.8%; 95% CI, 73.7%-73.9%) had a live delivery (mean [SD] age, 30.9 [5.4] years) and 167 522 (26.2%; 95% CI, 26.1%-26.3%) had a nonlive outcome (mean [SD] age, 31.6 [6.4] years). Of pregnancies with live deliveries, 5.8% (95% CI, 5.7%-5.8%) were exposed to teratogenic medications compared with 3.1% (95% CI, 3.0%-3.2%) with nonlive outcomes. Median time to prenatal care was 56 days (IQR, 44-70 days). By 6 weeks' gestation, 8186 pregnancies had been exposed to teratogenic medications (25.2% [95% CI, 24.7%-25.7%] of pregnancies exposed at any time during gestation; 1.3% [95% CI, 1.3%-1.3%] of all pregnancies); in 6877 (84.0%; 95% CI, 83.2%-84.8%), prenatal care was initiated after 6 weeks or not at all. By 15 weeks, teratogenic exposures had occurred for 48.9% (95% CI, 48.4%-49.5%) of all teratogen-exposed pregnancies (2.5% [2.4-2.5] of all pregnancies); prenatal care initiation occurred after 15 weeks for 1810 (16.8%; 95% CI, 16.1%-17.5%) with live deliveries and 2975 (58.3%; 95% CI, 56.9%-59.6%) with nonlive outcomes. Teratogenic medications most used within the first 15 gestational weeks among live deliveries included antiinfectives (eg, fluconazole), anticonvulsants (eg, valproate), antihypertensives (eg, lisinopril), and immunomodulators (eg, mycophenolate). For nonlive deliveries, most antihypertensives were replaced by vitamin A derivatives. Conclusions and Relevance: In this cross-sectional study, most exposures to teratogenic medications occurred in early pregnancy and before prenatal care initiation, precluding prenatal risk-benefit assessments. Prenatal care commonly occurred after strict legal abortion cutoffs, prohibiting consideration of pregnancy termination if concerns about teratogenic effects arose.

Common teratogenic medication exposures-a population-based study of pregnancies in the United States.

BACKGROUND: Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposure. OBJECTIVE: This study aimed to identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons. STUDY DESIGN: We used the Merative™ MarketScan® Commercial Database to identify pregnancies with live or nonlive (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years from 2011 to 2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after the pregnancy end date. Medications with known or potential teratogenic risk were selected from TERIS (Teratogen Information System) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure on the basis of ≥1 outpatient pharmacy claim or medical encounter for medication administration during target pregnancy periods considering medication risk profiles (eg, risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, and abortion and postpartum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges in separating pregnancy-related indications, nor were opioids (because of complex risk-benefit considerations) or antiobesity medications if their only teratogenic mechanism was weight loss. RESULTS: Among all pregnancies, the 10 medications with known teratogenic risk and the highest prenatal exposures were sulfamethoxazole/trimethoprim (1988 per 100,000 pregnancy-years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Prevalence of exposure to sulfamethoxazole/trimethoprim decreased from 2346 to 1453 per 100,000 pregnancy-years from 2011 to 2018, but prevalence of exposure to vedolizumab increased 6-fold since its approval in 2015. Prenatal exposures in the first trimester were higher among nonlive pregnancies than among live-birth pregnancies, with the largest difference observed for warfarin (nonlive 370 vs live birth 78), followed by valproate (258 vs 86) and topiramate (1728 vs 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6495), metoprolol (1325), and atenolol (448). The largest first-trimester exposure differences between nonlive and live-birth pregnancies were observed for lithium (242 vs 89), gabapentin (1639 vs 653), and duloxetine (1914 vs 860). Steady increases in hydralazine and gabapentin exposures were observed during the study years, whereas atenolol exposure decreased (561 to 280). CONCLUSION: Several medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed for select teratogenic medications suggest that regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.

Medication Burden Among Pediatric Cancer Survivors: Analysis of a Population-Wide Electronic Database in Hong Kong.

BACKGROUND: Few studies have evaluated the medication burden borne by survivors of pediatric cancer. This study aimed to describe the drug utilization pattern of chronic medications in a cohort of young pediatric cancer survivors. METHODS: This was a population-based study of patients diagnosed with cancer at age 18 years or younger between 2000 and 2013 in Hong Kong and who had survived at least 5 years postdiagnosis. The primary outcome is the use of any chronic medication (medications that were prescribed for ≥30 consecutive days within a 6-month period). Multivariable log-binomial models were used to identify factors associated with chronic medication use. Kaplan-Meier analysis was used to present the cumulative proportion of survivors initiated on a chronic medication across time from cancer diagnosis. RESULTS: Of the 2444 survivors (median age = 22 years, interquartile range = 16-27 years), 669 (27.4%) required at least 1 chronic medication at least 5 years postdiagnosis. Survivors who developed a chronic health condition (CHC) had a 5.48 (95% confidence interval [CI] = 4.49 to 6.71) times higher risk of taking a chronic medication than those without CHC. At 10 years postdiagnosis, the cumulative proportion of survivors being initiated a chronic medication was 33.4% (95% CI = 31.1% to 35.6%) for the overall cohort. Higher cumulative proportions were observed in survivors with endocrine (74.6%, 95% CI = 68.4% to 79.6%), renal (68.8%, 95% CI = 54.2% to 78.7%), neurological (58.6%, 95% CI = 46.1% to 68.1%), and cardiovascular (54.7%, 95% CI = 44.0% to 63.4%) disorders. CONCLUSION: Survivors with certain CHCs had a higher risk of starting a prescription medication in the early phase of survivorship. Future studies include examining the impact of medication burden on survivors' functional status.

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.

A scoping review of nausea, vomiting and retching measurement methods in children with cancer.

Evaluation of chemotherapy-induced nausea and vomiting (CINV) in the pediatric population is subject to diverse approaches. This scoping review summarizes the methods used in clinical studies that assessed nausea, vomiting or retching in children with cancer. We conducted a literature search of studies indexed in EMBASE and Ovid MEDLINE after 2000. Studies were included if they involved patients ≤18 years of age diagnosed with cancer, and had nausea, vomiting or retching as a primary study outcome. We excluded studies that reported only parent- or clinician-proxy measures without including the child's self-reported NVR, and those without specifying the NVR data collection process. The literature search identified twenty-four studies evaluating pediatric nausea, vomiting or retching. In the assessment of NVR, structured surveys were the most commonly used instrument for NVR assessment (75%) and the use of patient diaries (50%). Nine studies (38%) relied solely on self-reports from children as the outcome measure, while fifteen studies (62%) solicited input from parents/ caregivers and healthcare providers in addition to children's self-reports. Almost all the studies reported the frequency (n = 24) and/or severity (n = 23) of NVR symptoms and the use of antiemetic therapy (n = 19). Fewer studies evaluated distress caused by the symptoms (n = 2) and the effects of symptoms on activities of daily living (n = 4). Incorporating NVR measurement tools as part of standard of care for pediatric patients undergoing chemotherapy is strongly advocated. Based on the age group, we recommend the use of such tools comprising Likert scale, pictorial scales and structured scripts to assess various dimensions of a child's NVR experience.

Using Electronic Health Records for Personalized Dosing of Intravenous Vancomycin in Critically Ill Neonates: Model and Web-Based Interface Development Study.

BACKGROUND: Intravenous (IV) vancomycin is used in the treatment of severe infection in neonates. However, its efficacy is compromised by elevated risks of acute kidney injury. The risk is even higher among neonates admitted to the neonatal intensive care unit (NICU), in whom the pharmacokinetics of vancomycin vary widely. Therapeutic drug monitoring is an integral part of vancomycin treatment to balance efficacy against toxicity. It involves individual dose adjustments based on the observed serum vancomycin concentration (VCs). However, the existing trough-based approach shows poor evidence for clinical benefits. The updated clinical practice guideline recommends population pharmacokinetic (popPK) model-based approaches, targeting area under curve, preferably through the Bayesian approach. Since Bayesian methods cannot be performed manually and require specialized computer programs, there is a need to provide clinicians with a user-friendly interface to facilitate accurate personalized dosing recommendations for vancomycin in critically ill neonates. OBJECTIVE: We used medical data from electronic health records (EHRs) to develop a popPK model and subsequently build a web-based interface to perform model-based individual dose optimization of IV vancomycin for NICU patients in local medical institutions. METHODS: Medical data of subjects prescribed IV vancomycin in the NICUs of Prince of Wales Hospital and Queen Elizabeth Hospital in Hong Kong were extracted from EHRs, namely the Clinical Information System, In-Patient Medication Order Entry, and electronic Patient Record. Patient demographics, such as body weight and postmenstrual age (PMA), serum creatinine (SCr), vancomycin administration records, and VCs were collected. The popPK model employed a 2-compartment infusion model. Various covariate models were tested against body weight, PMA, and SCr, and were evaluated for the best goodness of fit. A previously published web-based dosing interface was adapted to develop the interface in this study. RESULTS: The final data set included EHR data extracted from 207 subjects, with a total of 689 VCs measurements. The final model chosen explained 82% of the variability in vancomycin clearance. All parameter estimates were within the bootstrapping CIs. Predictive plots, residual plots, and visual predictive checks demonstrated good model predictability. Model approximations showed that the model-based Bayesian approach consistently promoted a probability of target attainment (PTA) above 75% for all subjects, while only half of the subjects could achieve a PTA over 50% with the trough-based approach. The dosing interface was developed with the capability to optimize individual doses with the model-based empirical or Bayesian approach. CONCLUSIONS: Using EHRs, a satisfactory popPK model was verified and adopted to develop a web-based individual dose optimization interface. The interface is expected to improve treatment outcomes of IV vancomycin for severe infections among critically ill neonates. This study provides the foundation for a cohort study to demonstrate the utility of the new approach compared with previous dosing methods.

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.

Stress and Perception of Procedural Pain Management in Chinese Parents of Children With Cancer.

OBJECTIVES: Children with cancer are exposed to repeated painful and invasive procedures. This study examines Chinese parents' stress and perception toward their children's procedural pain control. METHODS: We recruited 265 parents of children (aged <18 years) diagnosed with hematological cancer (74.7%) and solid tumors (25.3%) from two major public hospitals. Parents used a scale (0-10) to rate perceived pain experienced by their child when undergoing lumbar puncture (LP), bone marrow aspirate, or/and biopsy. They reported their stress level and attitudes toward analgesics using the adapted Pain Flexibility Scale for Parents and Parental Medication Attitude Questionnaire. General linear modeling was used to identify factors associated with perception outcomes. RESULTS: Parents (72.8% mothers, age 36.5 [6.8] years) expressed that they were worried (31.7%) and had difficulty with concentration (57.7%) when the child was in pain. Among parents whose children had undergone LP (n = 207), 39.1% perceived that their child still experienced severe pain (pain score >7) even with existing pain control measures. Parents reported concerns over side effects of analgesics (69.4%) and addiction (35.1%). Half of the parents (47.2%) perceived that analgesics should only be reserved for severe pain. Parents who were older (estimate = 2.07, SE = 0.87; P = 0.0054) and had lower education attainment (estimate = -3.38, SE = 1.09; P = 0.0021) had a more negative attitude toward analgesics use. Higher parental distress was associated with avoidance of analgesics use (rs = 0.17, P = 0.0052). CONCLUSION: Our findings suggested that subgroups of Chinese parents demonstrated distress with their child's pain and harbored misconceptions over analgesics use. Future work includes devising targeted psychoeducation interventions for these parents.

Vancomycin Prescribing Practices and Therapeutic Drug Monitoring for Critically Ill Neonatal and Pediatric Patients: A Survey of Physicians and Pharmacists in Hong Kong.

Background: Deviations from the optimal vancomycin dosing may occur in the neonatal and pediatric population due to inconsistencies in the recommended dosing algorithms. This study aims to collect the expert opinions of clinicians who practice in the neonatal or pediatric intensive care units (NICU/PICUs) of 12 major medical centers in Hong Kong. Methods: This was a multicenter, cross-sectional study. Eligible physicians and pharmacists completed a structured questionnaire to identify the challenges they encountered when selecting the initial intermittent vancomycin dosing. They also answered questions concerning therapeutic monitoring services (TDM) for vancomycin, including the targeted trough levels for empirical vancomycin regimens administered for complicated and uncomplicated infections. Results: A total of 23 physicians and 43 pharmacists completed the survey. The top clinical parameters reported as most important for determining the initial vancomycin dosing were renal function (90.9%), post-menstrual/postnatal age (81.8%), body weight (66.7%), and suspected/documented pathogen (53.0%). Respondents reported challenges such as difficulties in determining the optimal initial dose for a targeted level (53.0%), inconsistencies between dosing references (43.9%) and a lack of clear hospital guidelines (27.3%). Half of the pharmacists (48.8%) reported that they had helped to interpret the TDM results and recommend vancomycin dose adjustments in >75% of cases. For methicillin-resistant Staphylococcus aureus infection, physicians, and pharmacists reported target trough levels of ~10-15 and 15-20 mg/L, respectively. For suspected moderate/uncomplicated Gram-positive infections physicians tended to prefer a lower trough range of 5-10 mg/L, while pharmacists preferred a range of 10-15 mg/L. Conclusions: Our results demonstrate that clinicians used varying vancomycin dosing guidelines in their practices. The multidisciplinary TDM service in Hong Kong can be improved further by establishing a standardized dosing guideline and implementing a well-structured, evidence-based service protocol. Future work includes conducting drug utilization studies to evaluate real-world antimicrobial usage patterns and the impact on tangible clinical outcomes, and developing pharmacokinetic-guided dose calculator for antimicrobials in critically ill neonates and pediatric patients.

Clinical ascertainment of health outcomes in Asian survivors of childhood cancer: a systematic review.

PURPOSE: Survivorship in children with cancer comes at a cost of developing chronic treatment-related complications. Yet, it is still an under-researched area in Asia, which shares the largest proportion of the global childhood cancer burden given its vast population. This systematic review summarizes existing literature on clinically ascertained health outcomes in Asian survivors of childhood cancer. METHODS: A search was conducted on Ovid Medline and EMBASE for studies that focused on survivors of childhood cancer from countries in East and Southeast Asia; adopted post-treatment clinical ascertainment of organ-specific toxicities or/and secondary malignancy. Studies were excluded if health outcomes were assessed during the acute treatment. RESULTS: Fifty-nine studies, enrolling a total of 13,442 subjects, were conducted on survivors of leukemia (34%), CNS tumor (14%), and cohorts of survivors with heterogeneous cancer diagnoses (52%). The studies used different medical evaluation methods to assess cardiovascular (15%), metabolic and infertility (32%), and neurological/neurocognitive (20%) outcomes in survivors. The collective findings suggest potential differences in the prevalence of certain late effects (e.g., secondary malignancy and obesity) among Asian and non-Asian populations, which may reflect differences in treatment regimens, practice, genetic variations, or/and socioeconomic disparity. CONCLUSIONS: We recommend developing collaborative initiatives to build a regional repository of systematically assessed health outcomes and biospecimens to investigate treatment, social-environmental and genetic predictors, and interventions for late effects in this population. IMPLICATIONS FOR CANCER SURVIVORS: The existing types of chronic health problems identified in this review suggest the need for active screening, better access to survivorship care, and promotion of protective health behavior in Asia.

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.