Diagnosis and Treatment of ADHD in the Pediatric Population.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016-2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients.

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease.

Objective: To review the efficacy and safety of crizanlizumab (Adakveo) in the prevention of vaso-occlusive pain crises in sickle cell disease. Data Sources: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to January 2021) was completed using the terms crizanlizumab, SEG101, SelG1, and sickle cell disease. Manufacturer prescribing information, article bibliographies, and data from clinicaltrials.gov were incorporated in the reviewed data. Study Selection/Data Extraction: All studies registered on clinicaltrials.gov were incorporated in the reviewed data. Data Synthesis: Crizanlizumab is the first monoclonal antibody approved for sickle cell disease to reduce the frequency of vaso-occlusive crises. One phase 2 clinical trial and a post hoc analysis of the trial have been published. Relevance to Patient Care and Clinical Practice: Crizanlizumab is a monthly intravenous infusion approved by the Food and Drug Administration for patients with sickle cell disease 16 years of age and older to reduce the frequency of vaso-occlusive crises. Conclusion: Crizanlizumab appears to be an efficacious therapy for patients with sickle cell disease to reduce the frequency of vaso-occlusive crises. Concerns include drug cost and administration. Long-term benefits and risks have not been determined.

Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy.

OBJECTIVE: To review the efficacy and safety of onasemnogene abeparvovec-xioi (Zolgensma) in the treatment of spinal muscular atrophy (SMA). DATA SOURCES: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to December 2019) was completed using the terms onasemnogene, AVXS-101, and spinal muscular atrophy. Manufacturer prescribing information, article bibliographies, and data from ClinicalTrials.gov were incorporated in the reviewed data. STUDY SELECTION/DATA EXTRACTION: All studies registered on ClinicalTrials.gov were incorporated in the reviewed data. DATA SYNTHESIS: Onasemnogene is the first agent for SMA utilizing gene therapy to directly provide survival motor neuron 1 (SMN1) gene to produce SMN protein. Four publications of 1 clinical trial, 1 comparison study of treatment effects, and 1 combination therapy case series have been published. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Onasemnogene is a one time dose approved by the Food and Drug Administration for SMA patients <2 years old who possess mutations in both copies of the SMN1 gene. CONCLUSION: Onasemnogene appears to be an efficacious therapy for younger pediatric patients with SMA type 1. Concerns include drug cost and potential liver toxicity. Long-term benefits and risks have not been determined.

A survey of pediatric degree option program graduates in a doctor of pharmacy curriculum: Confidence and initial employment position.

BACKGROUND AND PURPOSE: Graduates from the pediatric degree option program (PDOP) were tracked to identify confidence with pediatric pharmacotherapy and categorize initial employment following graduation. EDUCATIONAL ACTIVITY AND SETTING: The PDOP was established in 2011 and requires 16 credits of pediatric-focused didactic coursework and advanced pharmacy practice experiences. Thirty PDOP graduates completed a 30-item questionnaire to assess confidence in pediatric pharmacotherapy knowledge and skill statements and employment position following graduation. Responses were compared between those completing post-graduate pediatric pharmacy training and those who did not. FINDINGS: Nineteen (63.3%) graduates responded. All expressed "very high" or "high" confidence with dose calculations, first-line treatment selection for otitis media, and counseling caregivers on medications. However, <75% expressed "very high" or "high" confidence with identification of pharmacokinetic differences in neonates vs. children, utilization of growth charts, and counseling children. Ten (52.6%) respondents completed post-graduate training, and the remainder had an initial position in community or hospital pharmacy. There were no significant differences in pharmacotherapy skill and knowledge statements between those completing residency vs. those who did not. The most beneficial experiences reported were gaining clinical experience in pediatric pharmacy and medication safety. SUMMARY: Overall, PDOP graduates noted high confidence in pediatric pharmacotherapy skills and knowledge. Most felt that the PDOP influenced their initial career plans and made them more competitive for their initial position following graduation. The PDOP was well received and provided an opportunity for additional knowledge and skill development for students interested in pediatrics.

Impact of Electronic Health Record Systems on Prescribing Errors in Pediatric Clinics.

Medication errors are commonly reported in the pediatric population. While evidence supports the use of e-prescribing to prevent certain errors, prescribing with an electronic health record (EHR) system is not devoid of errors. Furthermore, the majority of EHRs are not equipped with functionalities addressing pediatric needs. This study analyzes three unique EHRs in three pediatric clinics. It describes the functionality of each system and identifies errors found in e-prescribed prescriptions. Finally, the study estimates the proportion of e-prescribing errors that could have been avoided if those EHRs had met requirements set by the American Academy of Pediatrics (AAP). The number of prescriptions reviewed for Clinics 1, 2, and 3, respectively, were: 477, 408, and 633 with total error rates of 13.2%, 8.8%, and 6.6%. The clinic EHRs included 21%, 26%, and 47% of the AAP pediatric requirements for safe and effective e-prescribing for children. If all AAP elements had been included in the EHRs, over 83% of errors in the examined e-prescriptions could have been prevented. This study demonstrates that EHR systems used by many pediatric clinic practices do not meet the standard set forth by the AAP. To ensure our most vulnerable population is better protected, it is imperative that medical technology tools adequately consider pediatric needs during development and that this is reflected in selected EHR systems.

Nusinersen: A Treatment for Spinal Muscular Atrophy.

OBJECTIVE: To review the efficacy and safety of nusinersen (Spinraza) in the treatment of spinal muscular atrophy (SMA). DATA SOURCES: An English-language literature search of PubMed and MEDLINE (1946 to June 2018) was performed using the terms nusinersen, ISIS-SMN (Rx), and spinal muscular atrophy. Manufacturer prescribing information, abstracts, article bibliographies, and clinicaltrials.gov data were incorporated for additional materials. STUDY SELECTION/DATA EXTRACTION: All clinical trials of nusinersen were identified and analyzed in the review. DATA SYNTHESIS: Nusinersen is the first drug therapy approved for the treatment of SMA. It is a novel modified antisense oligonucleotide designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron protein deficiency. Nusinersen has been studied for safety, pharmacokinetics, and efficacy in both open-label and randomized controlled trials. The studies show improvement in motor function across SMA of all types. The most common adverse effects were respiratory tract infections, headache, back pain, constipation, and post-lumbar puncture syndrome. Relevance to Patient Care and Clinical Practice: Based on phase III trial data, nusinersen produced positive changes in the clinical course of patients with SMA. The acquisition and administration of nusinersen present a number of challenges in clinical practice. Its intrathecal delivery and costly price tag must be recognized. CONCLUSION: Nusinersen is safe and effective in patients with SMA. It was well tolerated across all studied age groups.

Description of a pediatric degree option program in a doctorate of pharmacy curriculum and its impact on pediatric-focused advanced pharmacy practice experience rotations and faculty scholarly productivity.

PURPOSE: To describe the development of a Pediatric Degree Option program and its impact on pediatric-focused advanced pharmacy practice experiences (APPEs) and faculty scholarly productivity. EDUCATIONAL ACTIVITY: The Pediatric Degree Option program was established in 2011 and requires 16 h of didactic coursework and APPEs. The number of pediatric-focused APPEs and mean number of APPEs per pediatric faculty per year was compared pre- (2005-2010) and post-implementation (2011-2016). In addition, the median number of scholarship activities per student pre- and post-implementation was compared. The initial position obtained by graduates completing the degree option was collected. FINDINGS: Thirty students have completed the program. There were 146 pediatric-focused APPEs for the pre-implementation period and 259 post-implementation. However, there was an increase in pediatric faculty during the post-implementation, so there was no difference in the mean number of pediatric-focused APPEs per pediatric faculty in the pre- versus post-implementation period, 8.4 + 2.7 versus 6.9 +1.0, p = .224. A significant increase in the median number of pediatric-focused scholarly activities per student was observed pre-versus post-implementation, 3 (2-5) versus 5 (3-7), p = .005. Twenty-six (86.7%) students in the post-implementation period participated as a research assistant or coauthor in an original research or manuscript writing project. Students accepted a variety of positions after graduation including twelve (40%) accepting a PGY1 residency and eight (36.7%) as community pharmacists. SUMMARY: Although the number of pediatric-focused APPEs increased in the post-implementation, this did not result in an increase in the mean number of mean pediatric-focused APPEs per pediatric faculty member. However, it did allow a unique opportunity for 30 students with interest in pediatrics and allowed for content and skill development. The Pediatric Degree Option program allowed students to gain experience with pediatric-focused scholarly activities that also enhanced faculty productivity in scholarship and research.

Considerations for Providing Ambulatory Pharmacy Services for Pediatric Patients.

Pediatric clinical pharmacists are an integral part of the health care team. By practicing in an ambulatory care clinic, they can reduce the risk of medication errors, improve health outcomes, and enhance patient care. Unfortunately, because of limited data, misconceptions surrounding the role of pharmacists, and reimbursement challenges, there may be difficulty in establishing or expanding pediatric clinical pharmacy services to an ambulatory care setting. The purpose of this paper is to provide an overview of considerations for establishing or expanding pharmacy services in a pediatric ambulatory care clinic. The primer will discuss general and pediatric-specific pharmacy practice information, as well as potential barriers, and recommendations for identifying a practice site, creating a business plan, and integrating these services into a clinic setting.

Pharmacist-managed short-acting beta agonist refill service in a general pediatric clinic.

OBJECTIVES: To use a pharmacist-managed short-acting beta agonist (SABA) service (1) to determine the patient's rationale for SABA refill requests, (2) to assess adherence to current controller therapy and current level of disease control, and (3) to characterize the pharmacist's recommendations made in response to a patient's SABA refill request. SETTING: An academic-based general pediatric clinic. PRACTICE DESCRIPTION: SABA overuse is a marker of increased morbidity and mortality in children with asthma. This article describes a pharmacist-managed SABA refill telephone service. PRACTICE INNOVATION: The pediatric ambulatory care pharmacy team assessed and authorized (or denied) all SABA refill requests, provided education, and facilitated appropriate follow-up using a telephone service. INTERVENTIONS: Upon receiving a patient-requested SABA refill, the pharmacist identified the reason for the SABA request, assessed asthma control, and determined adherence to daily controllers or spacer use, if applicable. Education was also provided. Data obtained were used to determine SABA refill approval. EVALUATION: Primary reasons for SABA refill request were for (1) current symptom management and (2) no refills remaining in the absence of symptoms. Forty-two (50%) SABA refill requests were eligible for refill per the clinic algorithm, yet 70% actually received a refill after assessment by the pharmacist. Asthma control was assessed as 26% well controlled, 38% not well controlled, and 36% very poorly controlled. Forty-eight percent of patients prescribed daily controller medications were deemed adherent. Spacers were used in 43 of 76 (56%) patients using metered dose inhalers. Education was provided to 82% of caregivers. Pharmacists facilitated asthma follow-up visits in 41 of 84 (49%) patients contacted, and 61% of those appointments were kept. CONCLUSIONS: Pharmacist management of a SABA refill telephone service provides an additional means for delivery of asthma education, facilitates follow-up asthma care, helps to identify patients at risk for increased morbidity and mortality due to the overuse of SABAs, and provides another mechanism for medication refills.

Assessing guideline-concordant prescribing for community-acquired pneumonia.

Background Current reports of outpatient antimicrobial prescribing practices may overestimate guideline concordance since they address only drug selection. Appropriate stewardship should consider all prescribing criteria (i.e., dose, frequency, duration, and route of administration) to fully assess guideline concordance. Objective Using a community-acquired pneumonia (CAP) example, the aims of this pilot study were to estimate guideline concordance in adult patients 18 years or older when all prescribing criteria are considered, and provide recommendations to optimize treatment. Specific objectives were to determine which medications were most commonly prescribed for high-and low-risk patients, respectively, and determine if prescription parameters typically meet guideline recommendations. Methods This historical (retrospective) chart review at a large, non-emergent, outpatient academic practice included adult cases of CAP identified by ICD-9 codes, 481.x-486.x, 480.x and 487.x, diagnosed between July 1, 2014 and June 30, 2015. Patients were stratified into low- or high-risk categories based on presence of comorbidities and recent antibiotic use. Descriptive statistics were used to profile the sample and estimate aggregate guideline appropriateness, based on Infectious Disease Society of America/American Thoracic Society guidelines. Cases that were not prescribed an antibiotic at the index visit were excluded from assessment of concordance. Results Of the 101 total episodes identified, 49% were treated with an antibiotic. Of the 45 cases that met low-risk criteria, seven of the 24 treated cases (29%) received an appropriate antibiotic. When considering all prescription elements, all seven cases were congruent, for a composite concordance rate of 29%. Of the 56 cases that met high-risk criteria, 13 of the 25 treated cases (52%) received an appropriate antibiotic, although two cases were prescribed a suboptimal dose, and one case was prescribed a suboptimal duration, dropping composite concordance to 40%. Overall, prescribing was concordant in 17 of the 49 treated cases (35%). Conclusion Concordance with current guidelines in this local sample is suboptimal. In the low-risk group, when the correct medication was chosen, dose, duration, and frequency were appropriate. Consideration of dose and duration of treatment decreased the rate of concordant prescribing in the high-risk group.

Applicability of the Schwartz Equation and the Chronic Kidney Disease in Children Bedside Equation for Estimating Glomerular Filtration Rate in Overweight Children.

STUDY OBJECTIVE: To determine if significant correlations exist between glomerular filtration rate (GFR) prediction equation values, derived by using the original Schwartz equation and the Chronic Kidney Disease in Children (CKiD) bedside equation with a 24-hour urine creatinine clearance (Clcr ) value normalized to a body surface area of 1.73 m(2) in overweight and obese children. DESIGN: Prospective analysis (20 patients) and retrospective analysis (43 patients). SETTING: Pediatric inpatient ward and pediatric nephrology clinic at a comprehensive academic medical center. PATIENTS: Sixty-three pediatric patients (aged 5-17 years), of whom 27 were overweight (body mass index [BMI] at the 85th percentile or higher) and 36 were not overweight (BMI lower than the 85th percentile [controls]) between 2007 and 2012. METHODS AND MAIN RESULTS: Data from the overweight patients were compared with nonoverweight controls. GFR values were calculated by using the original Schwartz equation and the CKiD bedside equation. Each patient's 24-hour urine Clcr value normalized to a body surface area of 1.73 m(2) served as the index value. A Pearson correlation coefficient model was used to determine association between the 24-hour urine Clcr value (index value) with the Schwartz and CKiD GFR estimations. Significant correlation was found to exist between the Schwartz and CKiD bedside GFR estimations relative to the 24-hour urine Clcr in the control subjects (r = 0.85, p<0.0001, and r = 0.85, p<0.0001, respectively). Significant correlation was also found to exist between the Schwartz and CKiD bedside GFR values with the 24-hour urine Clcr value in overweight subjects (r = 0.86, p<0.0001, and r = 0.86, p<0.0001, respectively). The Schwartz equation estimated average GFR 21.75 ml/minute/1.73 m(2) higher than 24-hour urine Clcr (p<0.0001) in overweight children with a kidney disorder. The CKiD bedside GFR estimations were not significantly different compared with 24-hour urine Clcr values for the overweight group with kidney disorder (p=0.85). CONCLUSION: The Schwartz and CKiD bedside estimations of GFR correlated with 24-hour urine Clcr values in both overweight and nonoverweight children. Compared with the Schwartz equation, which tended to overestimate renal function, the CKiD bedside equation appeared to approximate 24-hour urine Clcr more closely in overweight children with kidney disorder.

Appropriateness of oral medication delivery devices available in community pharmacies.

OBJECTIVES: To identify the proportion of prescribed liquid medications that can be properly administered with devices available at local community pharmacies. METHODS: Prescriptions written over a 2-month time frame in a pediatric clinic were analyzed and compared with measuring devices available at community pharmacies within a 5-mile radius. Devices from the pharmacies were compared with the prescriptions to determine if they were acceptable and/or optimal to measure the dose as prescribed. Data collected for each prescription included items such as presence of markings on the device at the prescribed dose, if the units of measurement matched the device, if acceptable to measure the prescribed volume with the available device, optimal syringe volume, and if the pharmacy had an optimal device for the prescribed volume. RESULTS: Among the 11 different devices collected from the pharmacies, 5 different types were found. Over the 2 months of prescription data analyzed, 557 prescriptions were written, with 158 (28%) being liquids requiring a medication delivery device for administration. When comparing the 5 unique devices to 158 prescriptions independently, it was found that 9%, 30%, 53%, and 92%, respectively, for the 1-mL, 3-mL, 5-mL, and 10-mL devices were acceptable to measure the volume prescribed. The 5-mL syringe was optimal in only 21% of prescriptions analyzed, and the 10-mL syringe and spoon were found to be the most optimal device for the prescriptions analyzed. Of the 5 pharmacies reviewed, all prescriptions could be optimally measured with the use of devices that they had available 49% of the time (range 22% to 78%). CONCLUSION: Oral medication delivery devices are imperative for safe and effective oral liquid medication use. Understanding optimal and acceptable devices would allow pharmacists to tailor patient-specific education and would allow direction when stocking oral delivery devices in the community pharmacy.

Role of Clonidine in Neonatal Abstinence Syndrome: A Systematic Review.

OBJECTIVE: To provide a systematic review of the current role of clonidine in neonatal abstinence syndrome (NAS). DATA SOURCES: A MEDLINE literature search inclusive of the dates 1946 to November 2015 was performed using the search terms clonidine and abstinence syndromes, neonatal. Excerpta Medica was searched from 1980 to November 2015 using the search terms clonidine and newborn. Additionally, Web of Science was searched using the terms clonidine and neon* inclusive of 1945 to November 2015. STUDY SELECTION AND DATA EXTRACTION: We utilized the PRISMA guidelines to select English language, human primary literature, review articles, and supporting data assessing the efficacy of clonidine in the treatment of NAS. DATA SYNTHESIS: Three clinical trials and 5 observational studies demonstrated evidence of clonidine's effectiveness in NAS. Clonidine's therapeutic use as monotherapy and in combination with other agents was shown to reduce the time needed for pharmacotherapy treatment. Adverse reactions associated with clonidine in neonates, when reported, are mild. CONCLUSION: The American Academy of Pediatrics recommends opioids as first-line agents in the treatment of NAS when pharmacological treatment is indicated. Limited data suggest that clonidine, in combination with other agents or as monotherapy, may be as effective, with minimal adverse effects and reduced treatment time. Prospective clinical trials are necessary to clarify the ultimate role of clonidine in NAS and establish long-term safety.

Identifying opportunities to improve medication management in transitions of care.

PURPOSE: The types and causes of medication discrepancies during the transition from inpatient to ambulatory care were investigated. METHODS: A descriptive study was conducted at an academic outpatient group practice affiliated with a private nonacademic hospital to (1) describe discrepancies between inpatient discharge summaries and patient-reported medication lists, (2) identify patient and system factors related to breakdowns in medication documentation, and (3) determine reasons for medication discrepancies. During a four-month period, 17 patients at high risk for medication misadventures while transitioning from hospital care to outpatient follow-up were contacted by telephone soon after discharge and asked to provide information on all medications they were taking. Patient-reported medication lists were compared with the corresponding discharge summaries, and medication discrepancies were categorized by patient- and system-level factors using a validated instrument. RESULTS: Of the total of 96 discrepancies identified, more than two thirds (n = 67, 68%) involved the omission of a prescribed medication from either the patient-reported list or the discharge summary. Cardiovascular medications, including antihypertensives, antilipemics, diuretics, and antiarrhythmics, accounted for almost one quarter of all medication discrepancies. About 15% (n = 14) and 16% (n = 15) of identified discrepancies related to medication dose and frequency, respectively. CONCLUSION: Among 17 patients transitioning from inpatient to outpatient care, nearly 100 discrepancies between patient-reported medication lists and discharge summaries were identified. Most discrepancies were attributed to nonintentional nonadherence and resumption of home medications without instructions to do so. All 17 patients had at least 1 medication discrepancy categorized as involving a system-level factor.

Pharmacist-led educational and error notification interventions on prescribing errors in family medicine clinic.

OBJECTIVES: To determine the rate of prescribing errors in a family medicine clinic and the subsequent impact of pharmacist-led educational and error notification interventions on prescribing errors. DESIGN: Single site, pre-post study design. SETTING: An outpatient academic family medicine clinic serving pediatric and adult populations in Oklahoma from March 1, 2011, through April 30, 2012. PARTICIPANTS: 24 resident physicians who prescribed medications during routine outpatient visits. INTERVENTION: A prescribing educational program, audit and feedback methods, and weekly newsletter. MAIN OUTCOMES MEASURE: Percentage of prescription errors and physician error rate before and after intervention among pediatric and adult populations. RESULTS: During the two assessment periods, 24 resident physicians wrote 2,753 prescriptions for 394 pediatric and 899 adult patients. The overall percentage of prescription errors decreased from 18.6% during March 2011 to 14.5% during April 2012 (P = 0.004). Errors were more commonly seen with prescriptions written for pediatric patients (24.9%) than for adult patients (13.9%) (P = 0.001). Individual physician error rates ranged from 5% to 36% (mean ± SD 16.5% ± 8.1). Physicians committed significantly fewer prescribing errors during the postintervention assessment period (14.9%) than during the preintervention assessment period (20.9%) (P = 0.002). Controlling for time, pediatric prescription error rates among physicians who participated in the educational intervention were 36% lower than the error rates among physicians who did not participate (rate ratio 0.64 [95% CI 0.45, 0.91], P = 0.01). CONCLUSION: The pharmacist-led educational program was effective in reducing pediatric prescribing errors among resident physicians in a family medicine clinic.