Development and use of an innovative Gap Finding Tool to create a Pharmaceutical Care Model within a paediatric oncology setting.

INTRODUCTION: A paediatric cancer ward is a setting where pharmacists participate in direct patient care, acting as coordinators between the patient, caregivers and healthcare professionals. The aim of the study was to develop a Gap Finding Tool to support the setting up of a pharmaceutical care model at a Paediatric-Adolescent Cancer Ward. METHODS: The Standards of Practice for Clinical Pharmacy Services by the Society of Hospital Pharmacists of Australia Committee of Specialty Practice in Clinical Pharmacy (2013), the American College of Clinical Pharmacy (2014) and the European Association of Hospital Pharmacists (2014) were used to compile the Gap Finding Tool. The developed Tool was tested for content validity by a panel of experts and subsequently implemented over 2 months. RESULTS: The Gap Finding Tool comprised of nine sections with an average of eight statements each about pharmacy services that should be provided at ward level. For each statement, the rater indicates whether these contributions are provided. When the Tool was implemented at the Paediatric-Adolescent Cancer Ward, four major gaps were identified, namely, absence of a clinical pharmacist, lack of medicines information, vetting of chemotherapy prescriptions by pharmacist with limited access to patient data and lack of pharmacist-input on medicines availability. Processes requiring optimisation included discharge medication advice and documentation processes. CONCLUSION: The developed Gap Finding Tool is an innovative tool which is versatile and can be used in ward or ambulatory clinical settings to identify gaps in pharmaceutical processes and services and compare national or regional practices to international standards.

Recommendations for Diagnosis and Prevention of Cytomegalovirus-Associated Necrotizing Enterocolitis in Breast-Fed Preterm Infants.

We present the case of a breast-fed preterm infant with postnatally acquired cytomegalovirus (CMV) and severe necrotizing enterocolitis (NEC) associated with CMV. The infant had persistent severe thrombocytopenia with clinical deterioration despite multiple platelet transfusions and maximal medical treatment. Surgical intervention was not feasible owing to the instability of the infant's condition. Upon identification of CMV in urine, intravenous ganciclovir was initiated with significant clinical improvement. We also present a literature review of cases of CMV-related NEC or other gastrointestinal complications in preterm and term infants.

The use of bumetanide for oliguric acute renal failure in preterm infants.

OBJECTIVE: To determine the effects of bumetanide in preterm infants with oliguric acute renal failure (OARF). STUDY DESIGN: Retrospective data review and multivariate analysis of urine output and serum creatinine, blood urea nitrogen, Na, K, Cl, and Ca levels before, during, and after bumetanide therapy in preterm infants with OARF whose conditions did not respond to furosemide therapy. RESULTS: A total of 35 infants received bumetanide for OARF after an initial trial of furosemide. Their birth weight, gestational age at birth, and postconceptional age at OARF were 811 ± 326 g, 26 ± 2.75 wks, and 29.2 ± 2.7 wks, respectively. Twenty-nine of the 35 infants (83%) responded to bumetanide. Seventeen of the 35 infants subsequently died in the hospital due to multiorgan dysfunction. For the survivors (n = 18) and 11 of 17 of nonsurvivors, urine output increased from 0.6 ± 0.6 mL/kg/hr to 3.0 ± 2.1 mL/kg/hr during bumetanide therapy (p < .0005). Serum creatinine levels increased from 2.13 ± 0.83 mg/dL to 2.3 ± 0.92 mg/dL (p = .04) during bumetanide treatment, whereas blood urea nitrogen levels decreased after bumetanide therapy from 38 ± 19 mg/dL to 31.67 ± 21.6 mg/dL (p = .049). No significant changes were noted in serum sodium, chloride, or calcium concentration. CONCLUSIONS: Bumetanide therapy significantly increased urine output within 24-48 hrs, but its use was associated with a transient increase in serum creatinine level. Bumetanide can be used in preterm infants to reverse oliguria when therapy with furosemide fails. Prospective, randomized, controlled trials with long-term follow-up in preterm infants are necessary to establish the usefulness of bumetanide for OARF.

Factors influencing antibiotic duration in culture-negative neonatal early-onset sepsis.

STUDY OBJECTIVE: Little guidance exists on the treatment duration of culture-negative early-onset sepsis (CN-EOS) in neonates, which may lead to prolonged antimicrobial therapy and adverse outcomes. Our objective was to identify risk factors associated with prolonged antibiotic therapy in CN-EOS in neonates. DESIGN: This was a retrospective, matched cohort study of neonates treated with empiric antibiotic therapy for EOS. Infants were sampled with matching of gestational age (GA) into short (≤3 days) and prolonged (>3 days) antibiotic course. Primary outcomes were to identify predictive factors that may be associated with prolonged therapy and compare rates of late-onset sepsis (LOS) and mortality. Secondary outcomes included necrotizing enterocolitis, feeding intolerance, and early development assessment. Predictors associated with prolonged antibiotic therapy were identified using multivariable-adjusted logistic regression. MEASUREMENTS AND MAIN RESULTS: Three hundred infants were included with 150 infants in each group. Mean GA and birthweights were 34.2 ± 4.7 weeks and 2293 ± 991 g, respectively. Male gender, 5-min Apgar <7, immature-to-total neutrophil ratio ≥0.2, C-reactive protein (CRP) ≥10 mg/L, need for vasopressors, and mechanical ventilation were identified as significant predictors for prolonged antibiotics in all infants. Independent of GA, elevated CRP (OR 40.84, 95% CI 15.28-109.15, p < 0.001), need for vasopressors (OR 13.48, 95% CI 3.86-47.15, p < 0.001), and mechanical ventilation (OR 12.98, 95% CI 4.91-34.35, p < 0.001) remained significant predictors of prolonged antibiotic use. Infants in the prolonged courses experienced significant delays in achieving independent oral feeding compared with infants receiving short-course antibiotics (median 17.5 vs. 8 days, p = 0.002, respectively). There were no significant differences in LOS, mortality, or other neonatal comorbidities. CONCLUSIONS: Elevated CRP levels, need for vasopressors, and mechanical ventilation were associated with prolonged antibiotic use in neonates presumptively treated for CN-EOS. Further research is warranted in identifying selective biomarkers for EOS and evaluating whether early antibiotic discontinuation for CN-EOS, despite abnormal laboratory tests/illness severity, is safe and justified.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Challenges of Vancomycin Dosing and Therapeutic Monitoring in Neonates.

Late-onset sepsis in neonates can lead to significant morbidity and mortality, especially in preterm infants. Vancomycin is commonly prescribed for the treatment of Gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and ampicillin-resistant Enterococcus species in adult and pediatric patients. Currently, there is no consensus on optimal dosing and monitoring of vancomycin in neonates. Different vancomycin dosing regimens exist for neonates, but with many of these regimens, obtaining therapeutic trough concentrations can be difficult. In 2011, the Infectious Diseases Society of America recommended vancomycin trough concentrations of 15 to 20 mg/L or an AUC/MIC ratio of ≥400 for severe invasive diseases (e.g., MRSA) in adult and pediatric patients. Owing to recent reports of increased risk of nephrotoxicity associated with vancomycin trough concentrations of 15 to 20 mg/L and AUC/MIC of ≥400, a revised consensus guideline, recently published in 2020, no longer recommends monitoring vancomycin trough concentrations in adult patients. The guideline recommends an AUC/MIC of 400 to 600, which has been found to achieve clinical efficacy while reducing nephrotoxicity. However, these recommendations were derived solely from adult literature, as there are limited clinical outcomes data in pediatric and neonatal patients. Furthermore, owing to the variation of vancomycin pharmacokinetic parameters among the neonatal population, these recommendations for achieving vancomycin AUC/MIC of 400 to 600 in neonates require further investigation. This review will discuss the challenges of achieving optimal vancomycin dosing and monitoring in neonatal patients.

Evaluation of the Risk Factors for Acute Kidney Injury in Neonates Exposed to Antenatal Indomethacin.

OBJECTIVE: Evidence is limited about important maternal and neonatal risk factors that affect neonatal renal function. The incidence of acute kidney injury (AKI) and identification of associated risk factors in neonates exposed to antenatal indomethacin was studied. METHODS: A retrospective cohort of neonates exposed to antenatal indomethacin within 1 week of delivery was analyzed for development of AKI up to 15 days of life. Adjusted hazard ratios (HRs) and 95% CIs for AKI risk were calculated in time-dependent Cox proportional hazards models. RESULTS: Among 143 neonates with mean gestational age of 28.3 ± 2.4 weeks, AKI occurred in 62 (43.3%), lasting a median duration of 144 hours (IQR, 72-216 hours). Neonates with AKI had greater exposure to postnatal NSAIDs (48.4% vs 9.9%, p < 0.001) and inotropes (37.1% vs 3.7%, p < 0.001) compared with neonates without AKI. In multivariable-adjusted models, increased AKI risk was observed with antenatal indomethacin doses received within 24 to 48 hours (HR, 1.6; 95% CI, 1.28-1.94; p = 0.036) and <24 hours (HR, 2.33; 95% CI, 1.17-4.64; p = 0.016) prior to delivery. Further, postnatal NSAIDs (HR, 2.8; 95% CI, 1.03-7.61; p = 0.044), patent ductus arteriosus (HR, 4.04; 95% CI, 1.27-12.89; p = 0.018), and bloodstream infection (HR, 3.01; 95% CI, 1.37-6.60; p = 0.006) were associated significantly with increased risk of AKI following antenatal indomethacin. Neonates with AKI experienced more bloodstream infection, severe intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, and longer hospitalization. CONCLUSIONS: Extended risk of AKI with antenatal indomethacin deserves clinical attention among this population at an already increased AKI risk.

Student Perspectives on a Collaborative International Doctorate of Pharmacy Program.

Objectives: To evaluate the educational experience and teaching methods of the collaborative Doctorate of Pharmacy (PharmD) program between the University of Malta (UM) and the University of Illinois at Chicago (UIC). Methods: A 41-question survey was developed to identify student demographics, satisfaction with the PharmD program and the utility of the current curricular components. Students who enrolled in the program in May 2017 were invited to participate. The survey contained open-ended, 5-point Likert, and multiple-choice type questions. The primary outcomes were the overall satisfaction and student motivations for pursuing the program. Secondary outcomes included the level of difficulty of courses, evaluation of assessment methods, and confidence in an interdisciplinary team. Results: Thirty-six students completed the survey (a response rate of 83.7%). The mean age was 30.1 ± 7.9 years. The majority of the students pursued the PharmD program to improve their knowledge, skills, and opportunity for obtaining a clinical position. The mean overall satisfaction of the program was 3.81 ± 1.1 (5 = very satisfied). Among the core courses, Pharmacotherapeutics had the highest overall satisfaction (4.45 ± 0.91) and level of difficulty (3.84 ± 0.51). Students felt that the tutorials/recitation case discussion sessions were the most effective teaching method (48.4%) and ranked faculties conducting case-based lectures highest for overall performance. Most students felt somewhat confident (54.8%) for participating in a multidisciplinary team. Conclusions: The UM/UIC PharmD Program is a unique program, utilizing a hybrid model of teaching, including distance education, to expose students to a broad and challenging curriculum in clinical pharmacy practice. Students are satisfied with this collaborative, international postgraduate PharmD program.

Juvenile Idiopathic Arthritis: A Focus on Pharmacologic Management.

Juvenile idiopathic arthritis is a chronic condition that affects many pediatric patients. It is a prevalent disease and has become the most common rheumatologic disease of childhood. The condition encompasses multiple different forms of chronic arthritides classified based on the location and number of joints affected as well as the presence or lack of a number of different inflammatory markers. The exact etiology is unknown but is thought to be multifactorial with genetic, humoral, and environmental factors playing a key role. Many pharmacologic agents are available for use in the treatment of juvenile idiopathic arthritis, with management involving the use of symptom-reducing agents and disease-modifying antirheumatic drugs. Treatment is not without adverse events, with many of the agents require monitoring regimens and patient education. Without treatment, the progression and chronicity of the disease can result in significant morbidity, with the potential for devastating consequences on the child's quality of life.

Comparison of the timing of initial prophylactic palivizumab dosing on hospitalization of neonates for respiratory syncytial virus.

PURPOSE: The effects of two prophylactic palivizumab schedules on hospitalization of neonates for respiratory syncytial virus (RSV) were compared. METHODS: This retrospective study was conducted in the neonatal intensive care unit (NICU) of a tertiary care, academic medical center. Patients were divided into two groups. Group 1 (hospitalized between October 2005 and April 2007) received inpatient doses of palivizumab monthly throughout the RSV season, regardless of their anticipated discharge date, followed by outpatient doses. Group 2 (hospitalized between October 2007 and April 2009) received only one dose of palivizumab before hospital discharge with subsequent outpatient doses. The primary outcome measure was the number of hospitalizations for RSV bronchiolitis. Secondary endpoints included the total number of palivizumab doses each patient received, number of inpatient doses per patient, number of hospitalizations requiring intensive care unit admission, patient need for mechanical ventilation, outcome of the RSV-related hospitalization, and cost of inpatient palivizumab doses per patient. RESULTS: A total of 207 neonates were included in the study (112 in group 1, 95 in group 2). The mean gestational age was 29.7 weeks in group 1 and 30.3 weeks in group 2. Seven patients were hospitalized for RSV infection (5 in group 1 versus 2 in group 2, p = 0.4564). No RSV-related deaths occurred. Significantly more inpatient doses were administered to group 1 versus group 2 (1.7 versus 1, p < 0.001). Limiting inpatient palivizumab to 1 dose before discharge resulted in an institutional cost savings of more than $60,000 annually. CONCLUSION: Hospitalization rates for RSV did not significantly differ between NICU patients who received inpatient prophylactic palivizumab monthly and those who received only one dose before discharge.

Patent ductus arteriosus in premature neonates.

Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a haemodynamically significant patent ductus arteriosus (PDA) can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation and increase the risk of bronchopulmonary dysplasia, intraventricular haemorrhage, renal dysfunction, cerebral palsy and mortality. We review the pathophysiology, clinical features and assessment of haemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of medical therapy for PDA, and can be used both for prophylaxis as well as for rescue therapy to achieve PDA closure. Surgical ligation is also effective and is used in infants who do not respond to medical management. Although both medical and surgical treatment have proven efficacy in closing the ductus, both modalities are associated with significant adverse effects. Because the ductus does undergo spontaneous closure in some premature infants, improved and early identification of infants most likely to develop a symptomatic PDA could help in directing treatment to the at-risk infants and allow others to receive expectant management.