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.

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.

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.