Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature

There have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies

Vancomycin-Associated Acute Kidney Injury in Critically Ill Adolescent and Young Adult Patients

Background: Risk factors for the development of vancomycin-associated acute kidney injury (AKI) have been evaluated in both pediatric and adult populations; however, no previous studies exist evaluating this in the critically ill adolescent and young adult patients. Objective: Identify the incidence of AKI and examine risk factors for the development of AKI in critically ill adolescents and young adults on vancomycin. Methods: This retrospective review evaluated the incidence of AKI in patients 15 to 25 years of age who received vancomycin, while admitted to an intensive care unit. Acute kidney injury in this population was defined as an increase in serum creatinine by 0.5 mg/dL or 50% from baseline. Patients who developed AKI were evaluated for specific risk factors compared to those who did not develop AKI. Results: A total of 50 patients (20 developed AKI) were included in the study. There was no difference in vancomycin daily dose or duration of vancomycin therapy. Maximum vancomycin trough (31.15 mg/dL vs 12.5 mg/dL, P = .006), percentage of patients with concurrent nephrotoxic medication (95% vs 60%, P = .012) and concurrent vasopressor (55% vs 23%, P = .029) were higher in those who developed AKI. Percentage of patients who underwent a procedure while on vancomycin (35% vs 6.7%, P = .021) was also higher within the AKI group. Conclusions: Vancomycin-associated AKI occurred in 40% of critically ill adolescent and young adult patients. These patients may be more likely to develop vancomycin-associated AKI if they had undergone a procedure, as well as in the presence of high vancomycin trough levels, concurrent nephrotoxic agents, and concurrent vasopressor therapy

Evaluating and Mitigating Risk of Acute Kidney Injury with the Combination of Vancomycin and Piperacillin-Tazobactam in Children

The antibiotic combination of vancomycin (VAN) and piperacillin-tazobactam (PTZ) has been associated with an increased risk of acute kidney injury (AKI) in both adult and pediatric patients. In this review, we highlight some of the limitations of existing pediatric studies evaluating the combination of VAN/PTZ, focusing on AKI risk in specific pediatric patient populations. We also review the variability in defining AKI in children and provide guidance to clinicians for use of prospective surveillance and stewardship in mitigating the risk of AKI in pediatric patients treated with combination of VAN/PTZ. Based on review of available pediatric studies, if the combination of VAN/PTZ is selected as an empirical antibiotic combination, it should be used in those at low risk for AKI and should be used with extreme caution in patients with additional nephrotoxic risks. Systems should be in place to monitor the use of VAN/PTZ and associated renal function in those receiving this antibiotic combination

A scalable life cycle inventory of an electrical automotive traction machine—part I: design and composition

Purpose: A scalable life cycle inventory (LCI) model of a permanent magnet electrical machine, containing both design and production data, has been established. The purpose is to contribute with new and easy-to-use data for LCA of electric vehicles by providing a scalable mass estimation and manufacturing inventory for a typical electrical automotive traction machine. The aim of this article (part I of two publications) is to present the machine design, the model structure, and an evaluation of the models’ mass estimations. Methods: Data for design and production of electrical machines has been compiled from books, scientific papers, benchmarking literature, expert interviews, various specifications, factory records, and a factory site visit. For the design part, one small and one large reference machine were constructed in a software tool, which linked the machines’ maximum ability to deliver torque to the mass of its electromagnetically active parts. Additional data for remaining parts was then gathered separately to make the design complete. The two datasets were combined into one model, which calculates the mass of all motor subparts from an input of maximum power and torque. The range of the model is 20–200 kW and 48–477 Nm. The validity of the model was evaluated through comparison with seven permanent magnet electrical traction machines from established brands. Results and discussion: The LCI model was successfully implemented to calculate the mass content of 20 different materials in the motor. The models’ mass estimations deviate up to 21% from the examples of real motors, which still falls within expectations for a good result, considering a noticeable variability in design, even for the same machine type and similar requirements. The model results form a rough and reasonable median in comparison to the pattern created by all data points. Also, the reference motors were assessed for performance, showing that the electromagnetic efficiency reaches 96–97%. Conclusions: The LCI model relies on thorough design data collection and fundamental electromagnetic theory. The selected design has a high efficiency, and the motor is suitable for electric propulsion of vehicles. Furthermore, the LCI model generates representative mass estimations when compared with recently published data for electrical traction machines. Hence, for permanent magnet-type machines, the LCI model may be used as a generic component estimation for LCA of electric vehicles, when specific data is lacking

A scalable life cycle inventory of an electrical automotive traction machine—part I: design and composition

Purpose: A scalable life cycle inventory (LCI) model of a permanent magnet electrical machine, containing both design and production data, has been established. The purpose is to contribute with new and easy-to-use data for LCA of electric vehicles by providing a scalable mass estimation and manufacturing inventory for a typical electrical automotive traction machine. The aim of this article (part I of two publications) is to present the machine design, the model structure, and an evaluation of the models’ mass estimations. Methods: Data for design and production of electrical machines has been compiled from books, scientific papers, benchmarking literature, expert interviews, various specifications, factory records, and a factory site visit. For the design part, one small and one large reference machine were constructed in a software tool, which linked the machines’ maximum ability to deliver torque to the mass of its electromagnetically active parts. Additional data for remaining parts was then gathered separately to make the design complete. The two datasets were combined into one model, which calculates the mass of all motor subparts from an input of maximum power and torque. The range of the model is 20–200 kW and 48–477 Nm. The validity of the model was evaluated through comparison with seven permanent magnet electrical traction machines from established brands. Results and discussion: The LCI model was successfully implemented to calculate the mass content of 20 different materials in the motor. The models’ mass estimations deviate up to 21% from the examples of real motors, which still falls within expectations for a good result, considering a noticeable variability in design, even for the same machine type and similar requirements. The model results form a rough and reasonable median in comparison to the pattern created by all data points. Also, the reference motors were assessed for performance, showing that the electromagnetic efficiency reaches 96–97%. Conclusions: The LCI model relies on thorough design data collection and fundamental electromagnetic theory. The selected design has a high efficiency, and the motor is suitable for electric propulsion of vehicles. Furthermore, the LCI model generates representative mass estimations when compared with recently published data for electrical traction machines. Hence, for permanent magnet-type machines, the LCI model may be used as a generic component estimation for LCA of electric vehicles, when specific data is lacking

Nephrotoxicity in a Patient With Inadequate Pain Control: Potential Role of Pharmacogenetic Testing for Cytochrome P450 2D6 and Apolipoprotein L1

A case is presented which demonstrates the perils of opioid inefficacy and how pharmacogenomic testing may have prevented nonsteroidal anti-inflammatory drug (NSAID)-induced nephrotoxicity and progression to chronic kidney disease (CKD). A 62 year-old female with back pain was treated with tramadol and hydrocodone; however, neither proved effective. Consequently, to control her pain, she resorted to cocaine, marijuana, and high dose nonsteroidal anti-inflammatory drugs (NSAIDs). She eventually developed CKD. To identify CKD contributors, she underwent genotyping for Apolipoprotein L1 (APOL1), a known risk factor of CKD, as well as relevant pharmacogenomic genes. Her APOL1 genotype was *G1(GM)/*G1(GM), placing her at increased risk of CKD progression. Her CYP2D6 genotype was *5/*17, consistent with intermediate metabolism, making opioid drugs reliant on CYP2D6 activation, such as tramadol and hydrocodone, relatively ineffective in this patient. Thus, this patient was at genetic risk for CKD and reduced opioid efficacy. We conclude that this genetic combination likely contributed to opioid inefficacy and the eventual progression to CKD

Diagnostic criteria for identifying individuals at high risk of progression from mild or moderate to severe alcohol use disorder

IMPORTANCE: Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnoses of substance use disorders rely on criterion count-based approaches, disregarding severity grading indexed by individual criteria. OBJECTIVE: To examine correlates of alcohol use disorder (AUD) across count-based severity groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether specific criteria within mild-to-moderate AUD differentiate across relevant correlates and manifest in greater hazards of severe AUD development. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved 2 cohorts from the family-based Collaborative Study on the Genetics of Alcoholism (COGA) with 7 sites across the United States: cross-sectional (assessed 1991-2005) and longitudinal (assessed 2004-2019). Statistical analyses were conducted from December 2022 to June 2023. MAIN OUTCOMES AND MEASURES: Sociodemographic, alcohol-related, psychiatric comorbidity, brain electroencephalography (EEG), and AUD polygenic score measures as correlates of DSM-5 AUD levels (ie, mild, moderate, severe) and criterion severity-defined mild-to-moderate AUD diagnostic groups (ie, low-risk vs high-risk mild-to-moderate). RESULTS: A total of 13 110 individuals from the cross-sectional COGA cohort (mean [SD] age, 37.8 [14.2] years) and 2818 individuals from the longitudinal COGA cohort (mean baseline [SD] age, 16.1 [3.2] years) were included. Associations with alcohol-related, psychiatric, EEG, and AUD polygenic score measures reinforced the role of increasing criterion counts as indexing severity. Yet within mild-to-moderate AUD (2-5 criteria), the presence of specific high-risk criteria (eg, withdrawal) identified a group reporting heavier drinking and greater psychiatric comorbidity even after accounting for criterion count differences. In longitudinal analyses, prior mild-to-moderate AUD characterized by endorsement of at least 1 high-risk criterion was associated with more accelerated progression to severe AUD (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared with prior mild-to-moderate AUD without endorsement of high-risk criteria (aHR, 5.64; 95% CI, 3.28-9.70), independent of criterion count. CONCLUSIONS AND RELEVANCE: In this cohort study of a combined 15 928 individuals, findings suggested that simple count-based AUD diagnostic approaches to estimating severe AUD vulnerability, which ignore heterogeneity among criteria, may be improved by emphasizing specific high-risk criteria. Such emphasis may allow better focus on individuals at the greatest risk and improve understanding of the development of AUD

Enhancing Pediatric Adverse Drug Reaction Documentation in the Electronic Medical Record

Adverse drug reactions (ADRs) often go unreported or are inaccurately documented in the electronic medical recorded (EMR), even when they are severe and life-threatening. Incomplete reporting can lead to future prescribing challenges and ADR reoccurrence. The aim of this study was to evaluate the documentation of ADRs within the EMR and determine specific factors associated with appropriate and timely ADR documentation. Retrospective data were collected from a pediatric hospital system ADR reports from October 2010 to November 2018. Data included implicated medication, type, and severity of reaction, treatment location, the presence or absence of ADR documentation in the EMR alert profile within 24 hours of the ADR hospital or clinic encounter discharge, ADR identification method, and the presence or absence of pharmacovigilance oversight at the facility where the ADR was treated. A linear regression model was applied to identify factors contributing to optimal ADR documentation. A total of 3065 ADRs requiring medical care were identified. Of these, 961 ADRs (31%) did not have appropriate documentation added to the EMR alert profile prior to discharge. ADRs were documented in the EMR 87% of the time with the presence of pharmacovigilance oversight and only 61% without prospective pharmacovigilance (P < .01). Severity of ADR was not a predictor of ADR documentation in the EMR, yet the implicated medication and location of treatment did impact reporting. An active pharmacovigilance service significantly improved pediatric ADR documentation. Further work is needed to assure timely, accurate ADR documentation