bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Rice Research: Current Status and Prospects
Authors: Rout Diptibala , Jena Debarchana , Singh Vineeta , Kumar Manish , Arsode Pandurang , Singh Prakash , Lal Katara Jawahar , Samantaray Sanghamitra , Verma Ramlakhan
Published: October 2020

Heterosis is a solitary means of exploiting hybrid vigor in crop plants. Given its yield advantage and economic importance, several hybrids in rice have been commercialized in more than 40 countries, which has created a huge seed industry worldwide. India has made commendable progress and commercialized 117 three-line indica hybrids for different ecology and duration (115–150 days), which accounted for 6.8% of total rice area in the country. Besides, several indigenous CMS lines developed in diversified genetic and cytoplasmic backgrounds are being utilized in hybrid rice breeding. NRRI, which has been pioneering to start with the technology, has developed three popular rice hybrids, viz., Ajay, Rajalaxmi, and CR Dhan 701 for irrigated-shallow lowland ecosystem. Biotechnological intervention has supplemented immensely in excavating desirable genomic regions and their deployment for further genetic enhancement and sustainability in rice hybrids. Besides, hybrid seed production creates additional job opportunity (100–105 more-man days) and comparatively more net income (70% more than production cost) than HYVs. Hence, this technology has great scope for further enhancement in per se rice productivity and livelihood of the nation.
Localization Mechanisms of Radiopharmaceuticals
Authors: Komal Sana , Nadeem Sana , Faheem Zahra , Raza Arouma , Sarwer Komal , Umer Hijab , Roohi Samina , Ali Raza Naqvi Syed
Published: October 2020

Scintigraphic techniques have opened a new era of developments in the localization of infectious and cancerous foci. Diseases area targeting mechanisms of radiopharmaceuticals encompasses visualization, characterization, and measurement of physiological and biological functioning at targeted sites in addition to measure the area and density of the disease. The accumulation of a radiopharmaceutical at specific organ is based upon numerous processes such as enzymatic interactions, receptor binding site, transport of chemical species and elimination of damaged cells from circulation by a normal metabolic process. PET and SPECT are developing scanning techniques that provides effective diagnostic tool to identify pathophysiology of diseased cells. In this chapter, we are exploring and explaining different mechanisms of radiopharmaceutical localization for imaging and therapeutic processes. The knowledge of these mechanisms will help to develop target based new radiopharmaceuticals using variety of medically used radioisotopes either for imaging or therapy of diseased cells.
Nonlinear Frictional Dynamics on Rolling Contact
Authors: Sakai Yasunori
Published: October 2020

The rolling machine element is indispensable for realizing high-precision and high-speed relative motion. In addition, its positioning accuracy is approaching the nanometer order, and its importance is expected to increase in the future. However, since the rolling elements and the raceways are mechanically in contact, various nonlinear phenomena occur. This complicated phenomenon must be clear by theoretically and experimentally. This chapter describes the nonlinear friction behavior occurred with rolling contact condition and its effect on the dynamics of bearings. First, the characteristics of the non-linear friction caused by rolling machine elements and the nonlinear friction modeling method using the Masing rule are described. From the numerical analysis using the friction model, it is clarified that the motion accuracy decreases due to sudden velocity variation caused by nonlinear friction. Also, the author show that the resonance phenomenon and force dependency of the dynamic characteristics of rolling machine element due to the nonlinear friction. Finally, the author indicates nonlinear friction influences on the dynamic characteristics in the directions other than the feed direction.
Machine Learning in Volcanology: A Review
Authors: Carniel Roberto , Raquel Guzmán Silvina
Published: October 2020

A volcano is a complex system, and the characterization of its state at any given time is not an easy task. Monitoring data can be used to estimate the probability of an unrest and/or an eruption episode. These can include seismic, magnetic, electromagnetic, deformation, infrasonic, thermal, geochemical data or, in an ideal situation, a combination of them. Merging data of different origins is a non-trivial task, and often even extracting few relevant and information-rich parameters from a homogeneous time series is already challenging. The key to the characterization of volcanic regimes is in fact a process of data reduction that should produce a relatively small vector of features. The next step is the interpretation of the resulting features, through the recognition of similar vectors and for example, their association to a given state of the volcano. This can lead in turn to highlight possible precursors of unrests and eruptions. This final step can benefit from the application of machine learning techniques, that are able to process big data in an efficient way. Other applications of machine learning in volcanology include the analysis and classification of geological, geochemical and petrological “static” data to infer for example, the possible source and mechanism of observed deposits, the analysis of satellite imagery to quickly classify vast regions difficult to investigate on the ground or, again, to detect changes that could indicate an unrest. Moreover, the use of machine learning is gaining importance in other areas of volcanology, not only for monitoring purposes but for differentiating particular geochemical patterns, stratigraphic issues, differentiating morphological patterns of volcanic edifices, or to assess spatial distribution of volcanoes. Machine learning is helpful in the discrimination of magmatic complexes, in distinguishing tectonic settings of volcanic rocks, in the evaluation of correlations of volcanic units, being particularly helpful in tephrochronology, etc. In this chapter we will review the relevant methods and results published in the last decades using machine learning in volcanology, both with respect to the choice of the optimal feature vectors and to their subsequent classification, taking into account both the unsupervised and the supervised approaches.
Current Status of Antimicrobial Resistance and Prospect for New Vaccines against Major Bacterial Bovine Mastitis Pathogens
Authors: Kerro Dego Oudessa
Published: October 2020

Economic losses due to bovine mastitis is estimated to be $2 billion in the United States alone. Antimicrobials are used extensively in dairy farms for prevention and treatment of mastitis and other diseases of dairy cattle. The use of antimicrobials for treatment and prevention of diseases of dairy cattle needs to be prudent to slow down the development, persistence, and spread of antimicrobial-resistant bacteria from dairy farms to humans, animals, and farm environments. Because of public health and food safety concerns regarding antimicrobial resistance and antimicrobial residues in meat and milk, alternative approaches for disease control are required. These include vaccines, improvements in housing, management practices that reduce the likelihood and effect of infectious diseases, management systems and feed formulation, studies to gain a better understanding of animal behavior, and the development of more probiotics and competitive exclusion products. Monitoring antimicrobial resistance patterns of bacterial isolates from cases of mastitis and dairy farm environments is important for treatment decisions and proper design of antimicrobial-resistance mitigation measures. It also helps to determine emergence, persistence, and potential risk of the spread of antimicrobial-resistant bacteria and resistome from these reservoirs in dairy farms to humans, animals, and farm environments.
Low-Dose Aminophylline for the Treatment of Neonatal Non-Oliguric Renal Failure—Case Series and Review of the Literature
Authors: Lynch Bethany A. , Gal Peter , Ransom J. Laurence , Carlos Rita Q. , Dimaguila Mary Ann V.T. , Smith McCrae S. , Wimmer John E. , Imm Mitchell D.
Published: October 2020

OBJECTIVE Aminophylline is a methylxanthine with multiple physiologic actions. At low doses, aminophylline can antagonize adenosine and improve renal function via increased glomerular filtration rate. Despite its clinical use, little data exists in neonates for this indication. Therefore, the objective of this report is to describe the impact of aminophylline on renal function indices in a series of neonates with acute renal failure.

MATERIALS AND METHODS This was a retrospective chart review of 13 neonates with acute renal failure who received aminophylline during a 15-month study period. Aminophylline was administered at 1 mg/kg intravenously or orally every twelve hours. Forty-six percent (n = 6) of the patients received a 5 mg/kg loading dose before initiation of maintenance therapy. Most patients had already received other treatments for renal failure, including diuretics and dopamine.

RESULTS Resolution of acute renal failure (with normalization of serum creatinine and blood urea nitrogen) was documented in 10 patients (77%). Four of the thirteen patients died from complications due to their prematurity. Failure of low-dose aminophylline was observed in 3 of the 4 patients who died.

CONCLUSIONS Low-dose aminophylline in neonates with acute renal failure is associated with an improvement in renal function indices.
Elevated Tobramycin Concentrations Following Endotracheal Administration in a Premature Infant
Authors: Howard-Thompson Amanda , Christensen Michael L.
Published: October 2020

The following case report describes a 1-month-old, 34-week-gestation premature neonate who had compromised renal function. The neonate received endotracheally administered tobramycin (300 mg every 12 hours) via a PARI PLUS reusable nebulizer to treat a documented Gram-negative tracheostomy infection. The patient also received systemic tobramycin (2.5 mg/kg intravenously every 18 hours). The tobramycin serum concentration obtained 45 hours after the last intravenous dose and 11.5 hours after the second nebulized dose was 17.6 mg/L. The tobramycin nebulizations were stopped.
Combination Thrombolytic and Anti-Platelet Therapies in an Infant with Incomplete Kawasaki Disease and Coronary Aneurysms
Authors: Johnson Peter N. , Kuhn Robert J.
Published: October 2020

A 3-month-old infant was transferred to our facility with persistent fever and concerns for septic shock. A 2-D echocardiogram revealed multiple coronary aneurysms and axillary and coronary artery thrombi, and a diagnosis of incomplete Kawasaki disease (KD) was established. Aggressive therapies including intravenous immunoglobulins, enoxaparin, abciximab, aspirin, and alteplase were used to decrease the size of the coronary aneurysms and inhibit further thrombus formation. After minimal change in the size of coronary aneurysms and in thrombus formation, clopidogrel was added. Approximately 2 weeks after initiation of these therapies, a decrease in the coronary aneurysm size was noted with no signs of thrombus. This case documents successful use of thrombolytic and combination anti-platelet agents (i.e., clopidogrel, abciximab, and aspirin) in an infant with KD and cardiovascular sequelae.
Medication Management in Primary and Secondary Schools: Assessing the Practices and Opinions of Pediatricians
Authors: Reutzel Thomas J. , Baich Brandy L.
Published: October 2020

OBJECTIVES 1)To assess the awareness of pediatricians regarding the potential problems caused by children taking their medications before or during school hours 2) To identify the types of interventions pediatricians use to manage these issues 3)To assess the views of pediatricians regarding how well the process of medication management is handled by the schools that their patients attend.

METHODS Thirty-five pediatricians completed a questionnaire inquiring about their prescribing habits for children under the age of 18, their views on the possible effects medications may have on children while at school, and what they do to minimize problems that may be associated with taking or being under the influence of medications while at school.

RESULTS The largest group of responding physicians (42.9%; n = 15) selected “Somewhat Common” when asked how common it is that they prescribe medications that must be used before or during school hours. The majority of responding pediatricians surveyed (62%; n = 21) believe that taking medications at school can create special problems. The majority of respondents (59.4%; n = 19) disagree with the statement that “Medications in Illinois schools are well managed by a trained agent. These pediatricians utilize a variety of strategies to minimize problems caused by medication use during or before school, and the most common of these is the prescribing of sustained release products.

CONCLUSIONS Pediatricians who responded to a survey are aware of potential problems associated with children being under the influence of, or taking medications during school hours. As a result, many have devised ways to ameliorate and/or prevent potential problems.
Evaluation of the Two-Bag System for Fluid Management in Pediatric Patients with Diabetic Ketoacidosis
Authors: So Tsz-Yin , Grunewalder Elizabeth
Published: October 2020

OBJECTIVES A one-bag and a two-bag system have both been used to manage intravenous fluid administration in pediatric patients with diabetic ketoacidosis (DKA). The one-bag system, however, has been noted to have limitations, such as slow response time. This study evaluates whether the two-bag system provides any clinical benefit in pediatric DKA patients as compared to the one-bag system.

METHODS This was a retrospective, non-blinded chart review. Inclusion criteria were patients ≤ 18 years old and whose admission had the code of DKA as the diagnosis. Baseline clinical and demographic data were collected. Descriptive statistics were used in the data analysis.

RESULTS A total of 31 patients were included, 9 (29%) in the one-bag group and 22 (71%) in the two-bag group. Baseline characteristics were similar between the two groups. Mean (SD) rate of complete blood glucose (CBG) correction was 31.04 mg/dL/hr (20.61) in the two-bag group and 21.04 mg/dL/hr (16.26) in the one-bag group (p = 0.297). The rate of bicarbonate correction, however, was faster with the two-bag system than the one-bag system (0.949 ± 0.553 mEq/L/hr and 0.606 ± 0.297 mEq/L/hr, respectively) (p = 0.047). The two-bag system also had a faster time to ketone (p = 0.04), but not pH (p = 0.172), correction.

CONCLUSIONS The two-bag system provided a faster rate of bicarbonate and ketone correction compared to the one-bag system. The two-bag system also provided a trend towards a faster rate of blood glucose and pH correction.
Effects of Light Exposure on Total Parenteral Nutrition and its Implications in the Neonatal Population
Authors: Hoff David S. , Michaelson Amanda S.
Published: October 2020

Total parenteral nutrition (TPN) is a necessary form of nutrition in neonates with functional or anatomical disruption of the digestive tract. However, laboratory and human investigation have shown that exposure of the TPN solution to light causes the formation of peroxides and other degradation products that are quantifiable in experimental TPN solutions, laboratory animals, and neonates. Premature neonates are at a higher risk for the development and progression of peroxide damage due to their relative lack of antioxidant and free radical scavenger reserves. Furthermore, cell damage seen in a number of neonatal disease states is exacerbated by the presence of peroxides that are generated via intrinsic pathologic processes and from exogenous sources such as TPN. Numerous studies show that the formation of TPN photodegradation products can be slowed or prevented by the application of various light protection mechanisms. While it is not yet known if minimizing TPN associated photodegradation byproducts has a significant direct effect on preventing or mitigating the overall clinical course of some neonatal disease states, it is becoming increasingly clear that light protecting TPN can avoid specific metabolic complications in neonatal patients. It is prudent to implement mechanisms that prevent photodegradation of TPN components from the manufacturer source to the point of patient administration.
Dexmedetomidine Use in Pediatric Intensive Care and Procedural Sedation
Authors: Buck Marcia L.
Published: October 2020

OBJECTIVE

Dexmedetomidine was approved by the Food and Drug Administration in 1999 for the sedation of adults receiving mechanical ventilation in an intensive care setting. It provides sedation with minimal effects on respiratory function and may be used prior to, during, and following extubation. Based on its efficacy in adults, dexmedetomidine is now being explored as an alternative or adjunct to benzodiazepines and opioids in the pediatric intensive care setting. This review describes the studies evaluating the safety and efficacy dexmedetomidine in infants and children and provides recommendations on dosing and monitoring.

METHODS

The MEDLINE (1950–November 2009) database was searched for pertinent abstracts, using the key term dexmedetomidine. Additional references were obtained from the bibliographies of the articles reviewed and the manufacturer. All available English-language case reports, clinical trials, retrospective studies, and review articles were evaluated.

RESULTS

Over two dozen case series and clinical studies have documented the utility of dexmedetomidine as a sedative in children requiring mechanical ventilation or procedural sedation. In several papers, dexmedetomidine use resulted in a reduction in the dose or discontinuation of other sedative agents. It may be of particular benefit in children with neurologic impairment or in those who do not tolerate benzodiazepines. The most frequent adverse effects reported with dexmedetomidine have been hypotension and bradycardia, in 10% to 20% of patients. These effects typically resolve with dose reduction.

CONCLUSIONS

Dexmedetomidine offers an additional choice for the sedation of children receiving mechanical ventilation in the intensive care setting or requiring procedural sedation. While dexmedetomidine is well tolerated when used at recommended doses, it has the potential to cause hypotension and bradycardia and requires close monitoring. In addition to clinical trials currently underway, larger controlled studies are needed to further define the role of dexmedetomidine in pediatric intensive care.
The History of PPAG: The First 30 Years
Authors: Poole Robert L.
Published: October 2020

This article describes the history of the Pediatric Pharmacy Advocacy Group (PPAG). From its humble beginning in 1979, to its formation as the Pediatric Directors of Pediatric Hospitals in 1985, through its time as the Pediatric Pharmacy Administrative Group and through its evolution into the PPAG. The organization was established and continues to be dedicated to improving medication therapy use in children. Its sole purpose is to promote safe and effective medication use in children through communication, education, and research. After three decades, PPAG has established itself as the preeminent pediatric pharmacy organization. Its annual conference has grown over the years to become the best educational and networking meeting for pediatric pharmacists worldwide.
Use of Statins for Dyslipidemia in the Pediatric Population
Authors: Eiland Lea S. , Luttrell Paige K.
Published: October 2020

Childhood dyslipidemia is on the rise and increasingly being recognized as an important risk factor for adult cardiovascular disease. Due to a heightened awareness surrounding this problem, the American Academy of Pediatrics published a clinical report concerning prevention, screening, diagnosis, and treatment of dyslipidemia in children. Of concern among practitioners is when to initiate pharmacologic therapy and which medications are safe and appropriate in children. The report addresses this concern by suggesting that pharmacologic management begin only in pediatric patients with substantially elevated LDL levels. Since statins are the drugs of choice among adult patients with elevated LDL levels, it would be appropriate to evaluate their outcome in pediatric patients. To evaluate the efficacy and safety of statins for the treatment of pediatric dyslipidemia, a comprehensive search was performed of the MEDLINE database and International Pharmaceutical Abstracts as well as references from additional review articles. The manufacturer was contacted for data regarding a newly approved statin. Fourteen trials were identified, eight of which were randomized, controlled trials involving greater than 50 patients with primary or familial hypercholesterolemia. Overall, the studies showed that statins are effective at lowering LDL levels (reduction from baseline: 17% to 50%) and are fairly well tolerated, with headache, gastrointestinal distress, and myalgia being the most common adverse effects. Statins were found to be an efficacious option for the management of familial hypercholesterolemia of childhood. However, concerns regarding long term safety and efficacy have not been established, and data in patients with secondary lipid disorders is lacking.
Root Cause Analysis and Subsequent Intervention to Improve First Dose Antibiotic Turnaround Time for Hospitalized Pediatric Patients
Authors: Dee Abigail A. , Kelly Brian , Hampp Christian
Published: October 2020

OBJECTIVE

Antibiotic timing is used as a quality standard for hospital accreditation and is an important quality measure. The study aim was to identify barriers in the process of first dose antibiotic administration on the pediatric floors at a tertiary healthcare center and carry out and test an intervention to improve turnaround time to less than one hour.

METHODS

We conducted a quasi-experimental pre-post study of hospitalized pediatric patients up to 18 years of age initiated on intravenous antibiotics. Every order for a first dose intravenous antibiotic was assessed on all pediatric floors (10/2008). Orders that did not meet the overall turnaround time goal of ≤ 1 hour were identified. A root cause analysis (RCA) was performed to identify reasons for delayed antibiotic administration. Barriers identified in the RCA were used to develop interventions (03/2009) to improve compliance, and the proportion of orders that met the goal was compared pre- (10/2008–02/2009) and post-intervention (04/2009–05/2009).

RESULTS

During the pre-intervention assessment period, 32 out of 46 total physician orders for a first dose intravenous antibiotic did not meet the one-hour overall turnaround goal. A main reason for delay was failure to label antibiotic orders as first dose. We designed an intervention that included antibiotic audits and individualized feedback to prescribers. The mean ± SD time from the written physician order to drug administration was 228 ± 58 minutes; timing improved to 55 ± 4 minutes after the intervention. The proportion of antibiotics administered within one hour improved from 42.2% to 63% (p=0.0015).

CONCLUSIONS

We identified system barriers associated with delayed antibiotic administration. Antibiotic timing was improved after continued surveillance and individualized feedback to providers.
Pilot Comparison of Three Cardiopulmonary Resuscitation Medication Dosing Strategies in Overweight Children
Authors: Pinchevsky Lyndsy E. , Pesaturo Kimberly A. , Smith Brian S. , Hartman Christian A.
Published: October 2020

OBJECTIVES

Dose calculations using three variations of patient weight estimates (actual body weight [ABW], ideal body weight [IBW], and the Broselow Pediatric Emergency Tape [BPET, a length-based weight estimation tool]) were compared to administered doses of cardiopulmonary resuscitation medications in overweight and obese children to assess for differences in dose.

METHODS

This retrospective cohort analysis included 54 consecutive pediatric patients who underwent emergency resuscitation at UMass Memorial Medical Center between January 2000 and October 2008. Patients were identified using ICD-9 codes related to cardiopulmonary resuscitation. Patients were included if they were overweight or obese, less than 12 years of age, less than 146 centimeters in length, and received emergency resuscitation medication(s). Doses of administered medications were recorded and compared to potential doses calculated based on ABW, IBW and the dose recommended by the BPET. Dose differences greater than 10% were considered clinically significant and dose differences greater than 20% were considered to be potential medication errors.

RESULTS

Out of 54 possible patients, four overweight patients were included; none were obese. Ten total medication doses were assessed (minimum two per patient). In all patients, at least one comparator dose varied by greater than 20% from the administered dose. Four out of 10 doses calculated according to ABW, eight out of 10 doses calculated with IBW, and eight out of 10 doses recommended by the BPET all differed by greater than 20% from the administered dose.

CONCLUSIONS

Dosing variations were observed when the dose received was compared to dosing using three variants of patient weight estimates. The largest dosing differences were observed upon comparison of the administered dose versus the dose recommended by the BPET.
Omega-3 Long Chain Polyunsaturated Fatty Acids for Treatment of Parenteral Nutrition–Associated Liver Disease: A Review of the Literature
Authors: Tillman Emma M. , Helms Richard A.
Published: October 2020

Parenteral nutrition–associated liver disease (PNALD) is a complex disease that is diagnosed by clinical presentation, biochemical markers of liver injury, concurrent use of parenteral nutrition (PN), and negative workup for other causes of liver disease. For the past 30 years, clinicians have had few effective treatments for PNALD and when disease progressed to liver cirrhosis it was historically associated with poor outcomes. Within the past 5 years there has been some encouraging evidence for the potential benefits of fish oils, rich in omega-3 long-chain polyunsaturated fatty acids (ω3PUFA), in reversing liver injury associated with PN. This article reviews the current literature relating to ω3PUFA and PNALD.
Pharmacists' Perceived Knowledge and Expertise in Selected Pediatric Topics
Authors: Munzenberger Paul J. , Thomas Ron L. , Edwin Stephanie B. , Tutag-Lehr Victoria
Published: October 2020

OBJECTIVES

The purpose of this study is to determine pharmacists' perceived knowledge and expertise required to make recommendations regarding selected pediatric topics.

METHODS

A questionnaire was distributed to 400 pharmacists practicing in community, hospital, and home care settings. This instrument explored their perceived knowledge, expertise, and comfort in providing recommendations related to 38 pediatric topics. The impact of responder demographics on differences in perceived knowledge and expertise for each topic were evaluated.

RESULTS

Ninety-five of 400 (24%) questionnaires were returned completed or partially completed. Forty-seven and 36 of responders practiced in the community or inpatient hospital setting, respectively. Seventy percent of responders reported that ≤ 40% of their patients were children. In general, responders believed they had the knowledge and expertise to make recommendations for the frequently occurring conditions or topics but not for the less familiar. Formal pediatric training was the most influential responder characteristic with a larger proportion having training that they believed enables them to have knowledge and expertise to make recommendations. Although less impressive, experience of more than 5 years and a community-based practice were also important factors.

CONCLUSION

Additional training is beneficial in increasing the perceived knowledge and comfort of pharmacists making recommendations regarding pediatric patients.
Carbamazepine-Induced Acute Generalized Exanthematous Pustulosis: A Case Report
Authors: Skalli Saadia , Barret Pierre , Villier Céline , Bussières Jean-François
Published: October 2020

A 15-year-old adolescent was admitted to the hospital for management of a generalized pruritic skin rash, which had appeared 10 days prior to admission. Carbamazepine (CBZ) and insulin were initiated 44 and 23 days prior to the onset of the skin rash (day 44), respectively. Clinical examination showed bluish lesions on the tongue and bilateral keratoconjunctivitis. His skin was very erythematous and pruritic without edema and covered with hundreds of nonfollicular pustules mainly on the trunk and skin folds. Laboratory assessment revealed leukocytosis, hypereosinophilia, and thrombocytopenia. A sample of superficial pus from a pustule on the trunk showed a significant number of leukocytes as well as a significant number of Staphylococcus aureus and Lancefield Group B β-hemolytic streptococci strains. An abdominal skin biopsy revealed acute to subacute folliculocentric spongiotic dermatitis with subcorneal pustules. All of these observations were consistent with a diagnosis of acute generalized exanthematous pustulosis (AGEP). Although we could not exclude with certainty the role of insulin initiated on day 21 and discontinued on day 55 with substitution to oral metformin and repaglinide, no cases of AGEP have ever been published with insulin, and skin lesions were not related to injection sites. This article describes a probable case of CBZ-induced acute generalized exanthematous pustulosis in a 15-year-old adolescent.
The Role of the Pediatric Pharmacist in Personalized Medicine and Clinical Pharmacogenomics for Children
Authors: Kennedy Mary Jayne , Phan Hanna , Benavides Sandra , Potts Amy , Sorensen Susan
Published: October 2020

With the initiatives by the National Institutes of Health and the Food and Drug Administration, pharmacogenomics has now moved from the laboratory to the patient bedside. Over 100 drug-products now contain pharmacogenomic information as part of their labeling. Many of these are commonly used in the pediatric population. Direct-to-consumer genetic test kits also require intervention and guidance from healthcare professionals. This increased trend towards personalized medicine mandates that healthcare professionals develop a working knowledge about pharmacogenomics and its application towards patient care. Because pharmacogenomic testing can provide patient-specific predictors for response to and safety of medications, pharmacists are positioned to play an active role in pharmacogenomic testing, clinical interpretation of results, and recommendations for individualization of drug therapy. Opportunities for pharmacists exist in both inpatient and outpatient settings, such as pharmacist-managed clinical pharmacogenomics consultation services and educating patients and families about pharmacogenomic testing. In addition to clinical roles, pharmacists may also be involved in genetically-influenced drug discovery and development. Given the potential for genetic and age-dependent factors to influence drug selection and dosing, pediatric pharmacists should be involved in the development of dosing recommendations and interprofessional practice guidelines regarding pharmacogenomic testing in pediatric patients. Opportunities to become knowledgeable and competent in pharmacogenomics span from coursework as part of the pharmacy curriculum to postgraduate education (e.g., residencies, fellowships, continuing education). However, there exists a need for additional postgraduate learning opportunities for practicing pharmacists. As a result, the Pediatric Pharmacy Advocacy Group (PPAG) acknowledges a need for increased education of both student and practicing pharmacists, with consideration of special patient populations, such as infants and children. PPAG endorses and advocates for the involvement of pediatric pharmacists in pharmacogenomic testing and in using those results to provide safe and effective medication use in pediatric patients of all ages. Additionally, PPAG strongly encourages pediatric pharmacists to take responsibility for educating patients and their families about the importance of pharmacogenomic testing and its role in the safe and effective use of medications.
Assessment of Web-Based Training Modules on Learning Facilitation for Advanced Pharmacy Practice Experiences in Pediatrics
Authors: Morris Jennifer L. , Knoderer Chad A.
Published: October 2020

OBJECTIVES

To assess the effectiveness of web-based training (WBT) modules to enhance and facilitate student pharmacists' learning and their ability to provide pharmaceutical care to children during a pediatric advanced pharmacy practice experience (APPE).

METHODS

Pediatric-specific WBT modules were developed for completion by APPE students during a 4-week rotation. Pediatric modules covered developmental pharmacology; antimicrobial use and monitoring; fluids, electrolytes, and dehydration; and drug information. Students were responsible for completing all modules within the first week of the APPE. Preassessments and postassessments consisted of 8 to 10 multiple-choice questions, with scores ranging from 0 to 100 points. Data were analyzed using descriptive statistics and paired t tests.

RESULTS

Statistically significant improvements in postassessment scores were achieved for 3 of the 4 modules. Significant improvements were not observed in the antimicrobial use and monitoring module. Most student pharmacists either somewhat or strongly agreed that the modules improved their understanding of pharmaceutical care for children.

CONCLUSIONS

WBT modules, taken during an APPE rotation, may expand and improve student pharmacists' understanding of pharmaceutical care in pediatric patients.
Rhabdomyolysis Following a Short Course of Clarythromycin
Authors: Schor Anna M. , Hellerstein Ann
Published: October 2020

A healthy 5-year-old girl developed myalgia and an elevated creatine kinase concentration after 4 days of normal doses of clarithromycin. Myalgias resolved and creatine kinase values returned to normal following discontinuation of clarithromycin. No other precipitating factors or interacting drugs were identified; hence, clarithromycin was suspected as the cause of the rhabdomyolysis.
Formulation of Buprenorphine for Sublingual Use in Neonates
Authors: Anagnostis Ellena A. , Sadaka Rania E. , Sailor Linda A. , Moody David E. , Dysart Kevin C. , Kraft Walter K.
Published: October 2020

OBJECTIVES

The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration.

METHODS

Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each batch and placed in oral dispensing syringes for 3 and 7 days. Buprenorphine concentration was assessed by liquid chromatography–electrospray ionization–tandem mass spectrometry.

RESULTS

Neither storage temperature (p=0.65) nor storage time (p=0.24) significantly affected buprenorphine concentrations. All of the mean concentrations, regardless of storage temperature, were above 95% of the labeled concentration, and the potency was maintained for samples stored either in the original amber glass source bottles or in oral syringes.

CONCLUSIONS

An ethanolic buprenorphine solution is stable at room temperature for 30 days.
Treatment of Transient Neonatal Diabetes Mellitus with Subcutaneous Insulin Glargine in an Extremely Low Birth Weight Neonate
Authors: Barone Joseph V. , Tillman Emma M. , Ferry Robert J
Published: October 2020

Neonatal diabetes mellitus (NDM) results from impaired insulin secretion. While rare, NDM presents complex challenges with regard to the management of glycemic control. NDM is classified as transient neonatal diabetes mellitus (TNDM) or permanent neonatal diabetes mellitus (PNDM). Determination of TNDM vs. PNDM is usually possible only after medical management has been initiated. Management of NDM begins with insulin; however, the correct dose, choice of formulation, and route of administration are complicated by the risk of neonatal hypoglycemia. For the first time, the successful management of TNDM in an extremely low birth weight (ELBW) neonate with the long-acting subcutaneous insulin analog, insulin glargine, is reported. In addition, potential pharmacokinetic barriers to treating ELBW neonates diagnosed with NDM with subcutaneous insulin products are discussed.
A Systematic Review of the Pharmacokinetics of Antiepileptic Drugs in Neonates With Refractory Seizures
Authors: Tulloch Joanie K , Carr Roxane R , Ensom Mary H.H
Published: October 2020

BACKGROUND

Neonatal seizures are associated with neurological sequelae and an increased risk of epilepsy later in life. Phenobarbital and phenytoin remain the antiepileptic drugs (AEDs) most commonly used to treat neonatal seizures, despite their suboptimal effectiveness and safety. As a result, other AEDs, such as levetiracetam and topiramate, are often used in neonates with refractory seizures, despite limited data and off-label use.

OBJECTIVES

To systematically review published pharmacokinetic data for second-line AEDs used in neonates with seizures and to provide dosing recommendations for these agents in the neonatal population.

METHODS

A literature search was conducted in PubMed (1949-May 2012), Medline (1950-May 2012), and Embase (1980-May 2012). Each study was ranked according to the quality of evidence it provided, based on the classification system developed by the US Preventive Services Task Force. Information extracted from each study included study design, number of subjects, gestational and postnatal age, AED dosage regimen, pharmacokinetic parameters, pharmacokinetic model, AED serum concentrations, and sampling times.

RESULTS

Nineteen relevant pharmacokinetic studies involving a total of 8 different drugs were identified. No prospective, randomized, controlled studies (level I evidence) or nonrandomized controlled studies (level II-I evidence) were identified; 2 studies were prospective, nonrandomized, uncontrolled (cohort) studies (level II-2 evidence), 11 studies obtained evidence from multiple time series (level II-3 evidence), and 6 studies were case reports or descriptive studies (level III evidence).

CONCLUSIONS

There are limited pharmacokinetic data for the use of carbamazepine, levetiracetam, lidocaine, paraldehyde, topiramate, valproic acid, and vigabatrin for neonates with seizures refractory to treatment with first-line antiepileptic agents. Further research is needed to elucidate target AED serum concentrations (if any) required to optimize effectiveness and minimize dose-related adverse effects in neonates.
Treatment of Obesity in Children and Adolescents
Authors: Matson Kelly L , Fallon Renee M
Published: October 2020

The prevalence of childhood and adolescent obesity continues to rise in the United States (US). Immediate health consequences are being observed, and long-term risks are mounting within the pediatric population, secondary to obesity. The hallmark of prevention and treatment of obesity in children and adolescents includes lifestyle modification (i.e., dietary modification, increased physical activity, and behavioral modifications). However, when intensive lifestyle modification is insufficient to reach weight loss goals, adjunctive pharmacotherapy is recommended. Among the group of weight-loss medications, orlistat is the only US Food and Drug Administration (FDA)-approved prescription drug for the treatment of overweight and obese adolescents. Other medications, including metformin, need larger studies to establish their role in treatment. No single approach to management of pediatric obesity is the answer, given the complexity of the disorder and the many reasons for failure. Evidence of weight loss medications in addition to lifestyle modification supports short-term efficacy for treatment of obese children and adolescents, although long-term results remain unclear.
Relationship of Caffeine Dosing With Serum Alkaline Phosphatase Levels in Extremely Low-Birth-Weight Infants
Authors: Miller Jamie L , Nandyal Raja R , Anderson Michael P , Escobedo Marilyn B
Published: October 2020

OBJECTIVE

To determine whether patients receiving higher doses of caffeine have increased alkaline phosphatase (ALP) levels, as a biomarker for osteopenia.

METHODS

This descriptive, retrospective study included 152 extremely low-birth-weight infants (ie, <1 kg) admitted from January 1, 2007, to September 30, 2009, who received caffeine for >2 weeks. Patients were divided into a low-dose (<7.5 mg/kg/day) and high-dose (≥7.5 mg/kg/day) group based on maximum caffeine dose received. The primary objective was to compare peak ALP levels between groups. Secondary objectives included a comparison of caffeine regimens and risk factors for osteopenia between groups and identification of factors significantly related to increase in ALP. Between-group analysis was performed using the chi-squared or Fisher exact test and Wilcoxon Mann-Whitney median test or t-tests where appropriate. A linear regression model was used, with peak ALP as the dependent variable.

RESULTS

A majority of the patients (n=122) were included in the high-dose caffeine group. No significant difference in maximum ALP level between groups (median, 599.5, versus 602.5 units/L, p=0.72). Gestational age and birth weight were inversely related to ALP, whereas parenteral nutrition duration was directly related. No significant relationship between caffeine dose and ALP was identified.

CONCLUSIONS

In this preliminary study, using ALP as a biochemical marker for bone turnover, there does not appear to be a dose-related effect between ALP and caffeine dose.
Evaluation of Serum Concentrations Achieved With an Empiric Once-Daily Tobramycin Dosage Regimen in Children and Adults With Cystic Fibrosis
Authors: VandenBussche Heather L , Homnick Douglas N
Published: October 2020

OBJECTIVES

To assess the ability of an empiric once-daily dosing (ODD) tobramycin regimen to achieve desired serum concentrations in patients with cystic fibrosis (CF); to determine an optimal dosage regimen, using pharmacodynamic parameters; and to evaluate clinical response, adverse effects, and patient/parent satisfaction with ODD.

METHODS

This was a prospective single-center trial in patients with CF who are 5 years of age and older requiring intravenous antibiotics. Tobramycin, 10 mg/kg every 24 hours, was infused over 60 minutes, and two serum concentrations were analyzed using 1-compartment pharmacokinetic modeling. Simulations were performed to identify dosage regimens that maximized desired pharmacodynamic parameters. Other data included demographics, symptoms, spirometry, adverse events, and satisfaction with ODD.

RESULTS

A total of 14 children and 11 adults completed the study. Empiric doses resulted in mean peak tobramycin concentrations of 28.7 ± 5.5 mg/L and undetectable trough concentrations. Only 42% of patients achieved desired peak serum concentrations (20-30 mg/L) with the empiric regimen. A regimen of 12 mg/kg every 24 hours would achieve modified pharmacodynamic goals with an acceptable peak range of 20 to 35 mg/L. Forced expiratory volume in 1 second improved in 15 of 20 (75%) patients with ODD. Two patients experienced reversible vestibular adverse effects attributed to tobramycin. All patients were satisfied or very satisfied with ODD because of convenience and ease of use.

CONCLUSIONS

An empiric tobramycin regimen of 10 mg/kg every 24 hours did not achieve desired serum concentrations for most patients, although all patients demonstrated clinical improvement. Desired tobramycin concentrations with modified pharmacodynamic goals could be achieved by using an empiric dosage of 12 mg/kg every 24 hours. Prospective evaluation of this regimen with individualized patient monitoring is needed to ensure safety and efficacy and to monitor the effects on microbial resistance patterns.
Initial Experience With Conivaptan Use in Critically Ill Infants With Cardiac Disease
Authors: Jones Ryan C , Rajasekaran Surender , PharmD Mark Rayburn , Tobias Joseph D , Kelsey Robert M , Wetzel Glenn T , Cabrera Antonio G
Published: October 2020

OBJECTIVE

Arginine vasopressin (AVP) is the primary regulator of free water retention through its interactions with the AVP type 2 receptor (V2). As opposed to the natriuresis and diuresis that occur with loop and thiazide diuretics, conivaptan is an AVP V1A/V2 receptor antagonist, which enhances free water excretion while minimizing sodium loss. We report our preliminary experience with conivaptan to promote diuresis in infants with functional or structural cardiac disease.

METHODS

A retrospective cohort study was conducted of infants who had received conivaptan from August 2007 to January 2008. A loading dose of conivaptan (0.3-0.6 mg/kg) was followed by a continuous infusion of 0.01-0.02 mg/kg/hr for 24 hours. Sodium, potassium, chloride, blood urea nitrogen (BUN), creatinine, bicarbonate, and urine output were measured prior to the start of conivaptan and at 24 hours after initiation of the infusion.

RESULTS

Conivaptan was administered intravenously on 6 occasions to 5 patients with hypervolemic hyponatremia. Patients ranged in age from 8 to179 days, and body weight ranged from 3 to 4.12 kg. Mean sodium concentration increased from 130.17 ± 1.94 mEq/L to 133.67 ± 3.88 mEq/L (p=0.048), and median urine output increased from 4.15 to 5.05 mL/kg/hr (p=0.286). No significant changes were noted in serum potassium, bicarbonate, creatinine, or BUN. No adverse effects were noted during conivaptan infusion.

CONCLUSION

Intravenous conivaptan is effective for increasing serum sodium levels and may be a potential adjuvant to enhance diuresis in children with cardiac disease. Given the potential benefits of conivaptan compared to diuretic therapy, with all their potential complications, prospective trials are warranted.
Injectable Ammonium Chloride Used Enterally for the Treatment of Persistent Metabolic Alkalosis in Three Pediatric Patients
Authors: Mathew Jennie T , Bio Laura L
Published: October 2020

Enteral administration of injectable ammonium chloride may offer an effective method for the treatment of persistent metabolic alkalosis, without the adverse effects associated with the intravenous route. This case series describes 3 pediatric patients who received ammonium chloride enterally for the treatment of persistent metabolic alkalosis. The patients were a 2-month-old female infant, a 6-week-old male infant, and a 3-year-old male toddler. Four to 18 doses of ammonium chloride were administered enterally (range, 3-144 mEq/dose). Two of the 3 patients achieved resolution of metabolic alkalosis with ammonium chloride, while 1 patient's condition was refractory to treatment. Resolution of metabolic alkalosis occurred at 4 and 8 days, which required a total weight-based dose of 10.7 mEq/kg and 18 mEq/kg, respectively. No adverse effects were recorded. The use of ammonium chloride injection administered enterally was a safe and effective option in 2 of the 3 pediatric patients with persistent metabolic alkalosis.