I certainly did not expect to be standing here in front of you accepting the 2023 Richard A. Helms Award of Excellence in Pediatric Pharmacy Practice, in the company of so many people who I have admired, looked up to, and envied for their dedication to their careers, to the advancement of the profession each in their own way. Thank you to Rich Helms and to the Board of Directors for voting to give me this award. In some ways, I have always viewed the Helms Award as a symbol of lifetime achievements, and I don’t feel like I have
This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated. Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children. There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m2, older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated. The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.OBJECTIVE
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Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI−], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. The median (IQR) age of our cohort was 14 years (12–16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI−, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI− and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.OBJECTIVE
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Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center. Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data—hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments. Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb ≥10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb ≥10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb ≥10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia. Mircera appears safe and effective in pediatric patients with CKD.OBJECTIVE
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Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis.OBJECTIVE
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Pruritus is a common symptom of liver disease, managed with various medications including opioid antagonists like naltrexone. Current literature surrounding the safety and efficacy of naltrexone for cholestatic pruritus is limited. Our objective was to describe naltrexone prescribing practices for cholestatic pruritus. We conducted a single-center, retrospective review of inpatients who received naltrexone for cholestatic pruritus. We gathered information on naltrexone dosing, frequency, dose adjustments, duration, elevations in liver function tests (LFTs), and use of additional antipruritic agents. Thirty-nine patients and 122 dosing regimens were included for analysis. Most patients were male (56.4%) with a median age of 6.32 years (range, 0.63–18.89). The median weight-based doses of naltrexone were 1.45 mg/kg/dose (IQR, 0.84–2.81) and 1.86 mg/kg/day (IQR, 0.97–3.37). The median flat doses were 25 mg/dose (IQR, 12.25–50) and 50 mg/day (IQR, 25–50). The median number of additional antipruritic agents used before and after naltrexone initiation was 3 (IQR, 2–4) and 4 (IQR, 3–5), respectively (p < 0.001). The most common elevated LFTs were total bilirubin and alanine aminotransferase (ALT), occurring in 15% of patients. Naltrexone dosing ranged between 1 and 2 mg/kg/dose once or twice daily, with larger weight-based doses prescribed in younger and lower-weight patients. Naltrexone was commonly added as a fourth-line agent and did not lead to discontinuation of other antipruritic therapies. Larger, prospective, controlled studies are needed to assess the safety and efficacy of naltrexone for cholestatic pruritus.OBJECTIVE
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There are currently no data comparing outcomes of traditional vs pediatric-focused PGY1 residency programs. The primary objective of the survey was to identify if a difference in resident preparedness for a PGY2 pediatric pharmacy residency exists between these PGY1 program types. This survey-based study included all PGY2 pediatric residency program directors (RPDs) in 2021 and PGY2 pediatric pharmacy residents who completed residency between 2016–2020. Information regarding training paths of residents, such as type of PGY1 completed, and preparedness at the start of a PGY2 pediatric residency was collected. Preparedness for both general and pediatric-specific elements were assessed. A total of 101 respondents were included: 36 RPDs and 65 previous residents. RPDs felt residents who completed a pediatric-focused PGY1 were more prepared in baseline knowledge of pediatric diseases; otherwise, residents were similar across residency types in their perceived preparation for a PGY2. Pediatric-focused PGY1 residents felt significantly more prepared in pediatric baseline knowledge (96% vs 75%, p = 0.002) and managing pediatric emergencies (96% vs 50%, p = 0.002) than those who completed a traditional PGY1 program. There was no difference for patient care or clinical research skills. Residents in both groups obtained pediatric pharmacist jobs and felt equally prepared for transitioning into their first post-residency job. Despite a difference between the PGY1 resident groups in perceived baseline pediatric knowledge and preparedness to manage pediatric emergencies, similar post-residency jobs were obtained. Respondents felt equally prepared to begin their pediatric careers regardless of the type of PGY1 residency completed.Objective
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The purpose of this study was to describe overall screening, prevention, and treatments for pediatric delirium at various neonatal intensive care units (NICUs), cardiac intensive care units (CICUs), and pediatric intensive care units (PICUs) from the Pediatric Pharmacy Association (PPA) membership. The primary objective was to identify the number of respondents that had a defined delirium-based protocol. The secondary objectives included identification of delirium assessment tools used, first- and second-line delirium treatment options, and monitoring practices for antipsychotics for delirium management. A cross-sectional questionnaire was distributed to PPA members from February 8, 2022, to March, 25, 2022. Comparisons between the NICUs, PICUs, and CICUs were conducted by using chi-square tests, with a priori p value of <0.05 The questionnaire was completed by 84 respondents at 62 institutions; respondents practiced in the PICU or mixed PICU (n = 48; 57.1%), CICU (n = 13; 15.5%), and NICU (n = 23; 27.4%). Sixty-one respondents (72.6%) noted their units routinely screen for delirium, and there was a significant difference between the respondents of different units that use a delirium scoring tool (p < 0.01). Only 33 respondents (39.3%) had a defined delirium protocol, and there was no difference between units (p = 0.31). The most common agents used for delirium treatment were quetiapine and risperidone. There was variability in the monitoring used between respondents, but the majority (n = 74; 88%) monitor electrocardiograms to assess the corrected QT interval, but practice variability existed. Most respondents did not have a defined delirium protocol. Variations were noted in the treatment options and monitoring for critically ill pediatric patients with delirium.OBJECTIVES
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As broader spectrum antibiotics have been associated with adverse effects, our study evaluated whether the frequency of culture-positive late-onset sepsis (LOS) and multidrug resistant (MDR) infections were increased with the use of ceftazidime as compared with cefotaxime in the neonatal intensive care unit (NICU). This was a multihospital, retrospective chart review of patients who received at least 24 hours of ceftazidime or cefotaxime in the NICU between December 1, 2012 and August 31, 2021. Patients were excluded from analysis if they expired during the admission, had an incomplete history, positive cultures for an MDR infection prior to receiving either antibiotic, or received the alternate antibiotic within the same treatment course. A total of 334 patients were included for analysis (ceftazidime, n = 147; cefotaxime, n = 187). The average birth weight was lower in the ceftazidime cohort compared with the cefotaxime cohort [1.46 kg (95% CI, 1.29–1.63 kg) versus 1.93 kg (95% CI, 1.75–2.11 kg), p = 0.0002] with a corresponding lower gestational age [28.9 weeks (95% CI, 28.0–29.9 weeks) versus 31.7 weeks (95% CI, 30.8–32.6 weeks), p = 0.0001]. Adjusting for baseline differences showed a protective effect for ceftazidime (OR = 0.32; 95% CI, 0.16–0.62; p = 0.0009). There was no statistically significant difference in the frequency of MDR infections between the cohorts (OR = 0.25; 95% CI, 0.053–1.14; p = 0.07), however this study was underpowered to detect the difference noted. Ceftazidime appears to be a safe and effective alternative treatment option compared with cefotaxime in the NICU with no increase in the risk of culture-positive LOS or MDR infections.OBJECTIVE
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Methotrexate is an immunosuppressant commonly used in dermatology. The prevalence of intolerance using the Methotrexate Intolerance Severity Score (MISS) in pediatric juvenile idiopathic arthritis (JIA) ranges from 25% to 75%, but studies in morphea patients are lacking. We sought to determine the prevalence and predictors of methotrexate intolerance in children with morphea compared with children with inflammatory skin diseases and JIA/uveitis. Eligible patients were ages 2 to 18 years and were taking methotrexate for at least 3 months to treat morphea, inflammatory skin disease, or uveitis/JIA. Methotrexate intolerance was calculated using the MISS. A 1-way analysis of variance compared absolute intolerance scores. Multivariate regression analysis was used to compare MISS across diseases and covariates. Of 48 participants (mean ± SD age, 11.3 ± 4.1 years, 70.8% female), 15 had morphea, 16 had JIA/uveitis, and 17 had inflammatory skin diseases. The overall prevalence of intolerance was 20.8%. Age, sex, duration, and dose did not correlate with overall MISS. The MISS mean ± SD total for oral dosing was 2.5 ± 3.4, compared with 6.78 ± 6.8 for subcutaneous dosing. Patients with JIA/uveitis had the highest prevalence of intolerance (37.5%, n = 6), followed by morphea patients (20%, n = 3) and inflammatory skin disease patients (5.9%, n = 1). The OR of intolerance according to route of administration was 11.2 (95% CI, 2.03–61.89). Methotrexate intolerance was highest among patients with JIA/uveitis. The only predictor for risk of intolerance was subcutaneous route of administration. Future work could examine disease activity correlations and interventions designed to minimize intolerance.OBJECTIVE
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Included on the World Health Organization Model Lists of Essential Medicines, atropine remains a cornerstone medication that is used for a myriad of clinical indications. Systemically, atropine carries indications for the treatment of asymptomatic and symptomatic bradycardia, reduction of salivation and bronchial secretions prior to surgery, and as an antidote for a variety of poisoning agents (i.e., carbamate or organophosphate insecticides, nerve agents, muscarine-containing mushrooms). Topically, atropine is administered via the ophthalmic route for the treatment of cycloplegia, mydriasis, and amblyopia or may be administered sublingually to treat chronic sialorrhea. As an anticholinergic, supratherapeutic concentrations of atropine result in a toxidrome typical of other anticholinergic medication overdoses. However, it is easy to overlook atropine as the causative agent when being administered topically, potentially resulting in an unnecessarily extensive and complicated workup. This case report describes the systemic absorption of atropine administered through the ophthalmic route at normal doses, resulting in stroke-like symptoms in an adolescent male. Upon identifying that the patient was being treated with atropine ophthalmic drops prior to hospital arrival, a dose of intravenous physostigmine was administered, resulting in complete reversal of all toxidrome symptoms.
Children with central sleep apnea may require sedation for procedures, including brain imaging as part of the evaluation of apnea. However, the safety of deep sedation without a protected airway is not known in this patient population. In this case series, we present 3 children with central sleep apnea who were sedated with propofol for brain imaging in a non-operating room setting. All 3 did well with no complications; those with a home oxygen requirement were on oxygen during the procedure but none experienced apnea, desaturation, or respiratory distress. While obstructive sleep apnea is a known contraindication to deep sedation with propofol, it may be safe in pediatric patients with central sleep apnea. Deep sedation may be a good option for these patients, thereby avoiding the need for general anesthesia and placement of an advanced airway.
Over the last 20 years, there has been a significant increase in neonatal opioid withdrawal syndrome (NOWS) and it is currently estimated to affect 7.3 infants per 1000 hospital births.1 A clinical diagnosis of NOWS is established when an infant experiences withdrawal symptoms after birth because of in utero opioid exposure. The Finnegan Neonatal Abstinence Scoring System (FNASS), originally created as a research tool, has been used for many years to assess these patients and to determine the need for medical intervention. It involves subjectively assessing 21 nonspecific clinical signs, with a score of ≥8 indicating the
This commentary provides a concise step-by-step guide on using ChatGPT, an advanced natural language processing (NLP) model, for research and publication purposes. The guide assesses crucial aspects, including data preprocessing, fine-tuning techniques, prompt engineering, and ethical considerations. By addressing challenges related to biases, interpretability, and plagiarism, this commentary offers insights and recommendations for the responsible and ethical use of ChatGPT. The guide empowers researchers to ethically integrate ChatGPT effectively into their workflows, enhancing productivity and improving the quality of their scientific publications. Through clear instructions and guidelines, researchers can tap into the transformative potential of ChatGPT, driving scientific progressIntroduction
To the Editor.—I read with interest the article by DeVine et al1 on 3 pediatric patients with suprarefractory status epileptics (SRSE): patient 1, age 29 days, with traumatic brain injury; patient 2, age 52 days, with ischemic stroke due to venous malformation; and patient 3, age 60 days, with hypoxic brain injury, who benefited from ketamine continuously administered during 5 days in addition to a number of other antiseizure drugs. It was concluded that continuous ketamine infusion should be considered in SRSE.1 The study is compelling but has limitations that should be discussed. The main