A Pipeline for Real-Time Synchronization of Relevant Data in Pediatric Emergencies.

Pediatric emergencies are rare events that require precise medical intervention. The dosing of medication is particularly tricky. The challenges require technical aids for automatic dosage calculation without restricting the emergency physicians' ability to act. This short paper describes the development process of an automatic data processing pipeline that synchronizes multiple sensor data to perform the necessary calculations. In a final evaluation process, two transmission protocols (HTTP and MQTT)), are compared to determine which is more suitable for this application. The results of the evaluation clearly showed that MQTT is the preferred choice for the data processing pipeline due to its significantly lower latency.

Counting on Change: Conquering Challenges in Teaching Pharmaceutical Calculations.

All pharmacists are expected to accurately perform pharmaceutical calculations to ensure patient safety. In recent years, there have been trends in declining performance on the North American Pharmacist Licensure Examination related to calculations. Understanding the cause of this decline and determining methods to correct underlying issues could benefit pharmacy administration, faculty, students, and patients. The aims of this commentary are to present the factors impacting the students' pharmaceutical calculations abilities, discuss the consequences of declining math skills, and provide a call to action for scholarship of teaching and learning pertaining to calculations, as well as increased administrative support to rectify this challenge.

Assessing numeracy and medication calculations within undergraduate nursing education: A qualitative study.

AIM: To explore how undergraduate nursing students are assessed on nursing numeracy and medication calculations from the perspective of Australian nurse education leaders. DESIGN: A qualitative study. METHODS: Semi-structured interviews were conducted with 17 nurse education leaders between November 2022 and January 2023. Braun and Clarke's six phases of thematic analysis were used to analyse the data. RESULTS: Five key themes were identified: (i) high expectations to keep the public safe, (ii) diverse assessment formats, (iii) different ways of managing assessment integrity, (iv) assessment conditions incongruent to the clinical setting and (v) supporting struggling students. CONCLUSION: Nurse education leaders set high standards requiring students to achieve 100% in numeracy and medication calculation assessments, thus maintaining the reputation of nursing and patient safety. However, students struggled to meet this expectation. Diverse assessment formats were implemented, with some examination conditions contrary to clinical practice. Currently, there is no benchmark or independent point of registration examination in Australia, hence the problem is each university had a different standard to judge students' competence. Gaining insight into how these assessments are conducted provides an opportunity to work towards an evidence-based model or benchmark for the assessment of numeracy. IMPLICATIONS FOR THE PROFESSION: Dosage errors in clinical practice threaten patient safety and the reputation of the nursing profession. The accuracy rate of calculations by undergraduate and registered nurses is deficient worldwide. This research highlights a major educational issue, that being the wide variation in how numeracy assessments are conducted with no clear pedagogical rationale for a standardised method. Such assessments would establish a national standard, contributing to quality assurance, the development of the nursing profession and improve patient safety.

Variational autoencoders for generative modeling of drug dosing determinants in renal, hepatic, metabolic, and cardiac disease states.

Physiological determinants of drug dosing (PDODD) are a promising approach for precision dosing. This study investigates the alterations of PDODD in diseases and evaluates a variational autoencoder (VAE) artificial intelligence model for PDODD. The PDODD panel contained 20 biomarkers, and 13 renal, hepatic, diabetes, and cardiac disease status variables. Demographic characteristics, anthropometric measurements (body weight, body surface area, waist circumference), blood (plasma volume, albumin), renal (creatinine, glomerular filtration rate, urine flow, and urine albumin to creatinine ratio), and hepatic (R-value, hepatic steatosis index, drug-induced liver injury index), blood cell (systemic inflammation index, red cell, lymphocyte, neutrophils, and platelet counts) biomarkers, and medical questionnaire responses from the National Health and Nutrition Examination Survey (NHANES) were included. The tabular VAE (TVAE) generative model was implemented with the Synthetic Data Vault Python library. The joint distributions of the generated data vs. test data were compared using graphical univariate, bivariate, and multidimensional projection methods and distribution proximity measures. The PDODD biomarkers related to disease progression were altered as expected in renal, hepatic, diabetes, and cardiac diseases. The continuous PDODD panel variables generated by the TVAE satisfactorily approximated the distribution in the test data. The TVAE-generated distributions of some discrete variables deviated from the test data distribution. The age distribution of TVAE-generated continuous variables was similar to the test data. The TVAE algorithm demonstrated potential as an AI model for continuous PDODD and could be useful for generating virtual populations for clinical trial simulations.

Model-Informed Reinforcement Learning for Enabling Precision Dosing Via Adaptive Dosing.

Precision dosing, the tailoring of drug doses to optimize therapeutic benefits and minimize risks in each patient, is essential for drugs with a narrow therapeutic window and severe adverse effects. Adaptive dosing strategies extend the precision dosing concept to time-varying treatments which require sequential dose adjustments based on evolving patient conditions. Reinforcement learning (RL) naturally fits this paradigm: it perfectly mimics the sequential decision-making process where clinicians adapt dose administration based on patient response and evolution monitoring. This paper aims to investigate the potentiality of coupling RL with population PK/PD models to develop precision dosing algorithms, reviewing the most relevant works in the field. Case studies in which PK/PD models were integrated within RL algorithms as simulation engine to predict consequences of any dosing action have been considered and discussed. They mainly concern propofol-induced anesthesia, anticoagulant therapy with warfarin and a variety of anticancer treatments differing for administered agents and/or monitored biomarkers. The resulted picture highlights a certain heterogeneity in terms of precision dosing approaches, applied methodologies, and degree of adherence to the clinical domain. In addition, a tutorial on how a precision dosing problem should be formulated in terms of the key elements composing the RL framework (i.e., system state, agent actions and reward function), and on how PK/PD models could enhance RL approaches is proposed for readers interested in delving in this field. Overall, the integration of PK/PD models into a RL-framework holds great promise for precision dosing, but further investigations and advancements are still needed to address current limitations and extend the applicability of this methodology to drugs requiring adaptive dosing strategies.

Dosage Optimization: A Regulatory Perspective for Developing Oncology Drugs.

Optimized dosages provide a secure foundation for the development of well-tolerated and effective oncology drugs. Project Optimus, an initiative within the Oncology Center of Excellence, strives to reform the dosage optimization and dosage selection paradigm in oncology. This initiative stems from the availability of targeted drugs and from the demand for more tolerable dosages from patients, caregivers, and advocates. Reforming dosage optimization for oncology drugs requires a paradigm shift from the one employed for cytotoxic chemotherapy to one that understands and considers the unique attributes of targeted therapy, immunotherapy, and cellular therapy. Limited characterization of dosage during drug development may result in (1) patients not staying on a therapy long-term due to poor tolerability, (2) failure to establish positive benefit-risk in clinical trials for regulatory approval (3) withdrawal of drugs from the market (4) removal of indications of drugs from the market. Timely access to drugs is important for all patients with cancer, so it is vital to iteratively analyze all nonclinical and clinically relevant data at each stage of development and leverage quantitative approaches, innovative trial designs, and regulatory support to arrive at dosages with favorable benefit-risk. This review highlights the key challenges and opportunities to embracing this new paradigm and realizing the full potential of new oncology therapies.

Nurse academics' self-reported insights into the teaching of undergraduate nursing numeracy: A national cross-sectional study.

AIMS: The aim of this research was to explore the teaching of undergraduate nursing numeracy in tertiary education settings in Australia. Specifically, it explored and identified: (1) the most common basic numeracy concepts taught, (2) additional training and resources to support numeracy teaching, (3) who is best placed to teach numeracy and (4) the preferred methods of teaching medication calculations. BACKGROUND: Nurse academics are required to teach nursing numeracy to undergraduate nursing students who enter university unprepared to accurately calculate medication dosages. It is important that students understand numeracy concepts as this is then applied to contextualised clinical applications. Nurse academics teach basic numeracy; however, the literature reveals that nurse academics do not consider themselves mathematics teachers and that experts in this area are better suited to teaching this skill. There are a dearth of studies about the nurse academics who conduct the teaching and this study seeks to fill that gap by exploring firsthand the nurse academics' self-reported insights into the teaching of undergraduate nursing numeracy. DESIGN: Cross-sectional survey. The setting was Australian universities that deliver an accredited undergraduate nursing degree. METHODS: Purposive sampling was used to recruit Australian nurse academics (n = 170), sessional or permanent who currently teach all aspects of nursing numeracy and medication calculations to undergraduate nursing students. Data were collected between Nov 2023 - Feb 2024 using an online survey platform and analysed using a descriptive content analysis. RESULTS: Nurse academics taught basic arithmetic most commonly (92 %), yet most (90 %) had not received professional development or additional training in how to teach these concepts. To assist with numeracy teaching, resources were requested (47 %) as were the need for mathematics learning support staff (82 %). The formula method was most commonly taught (91 %), however, most participants (94 %) were willing to learn and to teach other methods of calculating medications. CONCLUSIONS: This research suggests an evidenced-based education framework be created to support and guide nurse academics when teaching all aspects of nursing numeracy and medication calculations. Building the teaching capacity of nurse academics in this vital area will enhance student competence and contribute to patient safety.

Calculating daily dose in the Observational Medical Outcomes Partnership Common Data Model.

PURPOSE: We aimed to develop a standardized method to calculate daily dose (i.e., the amount of drug a patient was exposed to per day) of any drug on a global scale using only drug information of typical observational data in the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) and a single reference table from Observational Health Data Sciences And Informatics (OHDSI). MATERIALS AND METHODS: The OMOP DRUG_STRENGTH reference table contains information on the strength or concentration of drugs, whereas the OMOP DRUG_EXPOSURE table contains information on patients' drug prescriptions or dispensations/claims. Based on DRUG_EXPOSURE data from the primary care databases Clinical Practice Research Datalink GOLD (United Kingdom) and Integrated Primary Care Information (IPCI, The Netherlands) and healthcare claims from PharMetrics® Plus for Academics (USA), we developed four formulas to calculate daily dose given different DRUG_STRENGTH reference table information. We tested the dose formulas by comparing the calculated median daily dose to the World Health Organization (WHO) Defined Daily Dose (DDD) for six different ingredients in those three databases and additional four international databases representing a variety of healthcare settings: MAITT (Estonia, healthcare claims and discharge summaries), IQVIA Disease Analyzer Germany (outpatient data), IQVIA Longitudinal Patient Database Belgium (outpatient data), and IMASIS Parc Salut (Spain, hospital data). Finally, in each database, we assessed the proportion of drug records for which daily dose calculations were possible using the suggested formulas. RESULTS: Applying the dose formulas, we obtained median daily doses that generally matched the WHO DDD definitions. Our dose formulas were applicable to >85% of drug records in all but one of the assessed databases. CONCLUSION: We have established and implemented a standardized daily dose calculation in OMOP CDM providing reliable and reproducible results.

Re-discover the value of protein binding assessments in hepatic and renal impairment studies and its contributions in drug labels and dose decisions.

One of the key pharmacokinetic properties of most small molecule drugs is their ability to bind to serum proteins. Unbound or free drug is responsible for pharmacological activity while the balance between free and bound drug can impact drug distribution, elimination, and other safety parameters. In the hepatic impairment (HI) and renal impairment (RI) clinical studies, unbound drug concentration is often assessed; however, the relevance and impact of the protein binding (PB) results is largely limited. We analyzed published clinical safety and pharmacokinetic studies in subjects with HI or RI with PB assessment up to October 2022 and summarized the contribution of PB results on their label dose recommendations. Among drugs with HI publication, 32% (17/53) associated product labels include PB results in HI section. Of these, the majority (9/17, 53%) recommend dose adjustments consistent with observed PB change. Among drugs with RI publication, 27% (12/44) of associated product labels include PB results in RI section with the majority (7/12, 58%) recommending no dose adjustment, consistent with the reported absence of PB change. PB results were found to be consistent with a tailored dose recommendation in 53% and 58% of the approved labels for HI and RI section, respectively. We further discussed the interpretation challenges of PB results, explored treatment decision factors including total drug concentration, exposure-response relationships, and safety considerations in these case examples. Collectively, comprehending the alterations in free drug levels in HI and RI informs treatment decision through a risk-based approach.

Assessment of Dosing Strategies for Pediatric Drug Products.

Pediatric drug dosing is challenged by the heterogeneity of developing physiology and ethical considerations surrounding a vulnerable population. Often, pediatric drug dosing leverages findings from the adult population; however, recent regulatory efforts have motivated drug sponsors to pursue pediatric-specific programs to meet an unmet medical need and improve pediatric drug labeling. This paradigm is further complicated by the pathophysiological implications of obesity on drug distribution and metabolism and the roles that body composition and body size play in drug dosing. Therefore, we sought to understand the landscape of pediatric drug dosing by characterizing the dosing strategies from drug products recently approved for pediatric indications identified using FDA Drug Databases and analyze the impact of body size descriptors (age, body surface area, weight) on drug pharmacokinetics for several selected antipsychotics approved in pediatric patients. Our review of these pediatric databases revealed a dependence on body size-guided dosing, with 68% of dosing in pediatric drug labelings being dependent on knowing either the age, body surface area, or weight of the patient to guide dosing for pediatric patients. This dependence on body size-guided dosing drives the need for special consideration when dosing a drug in overweight and obese patients. Exploratory pharmacokinetic analyses in antipsychotics illustrate possible effects of drug exposure when applying different dosing strategies for this class of drugs. Future efforts should aim to further understand the pediatric drug dosing and obesity paradigm across pediatric age ranges and drug classes to optimize drug development and clinical care for this patient population.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation. We compared the percentage of time spent in the international normalized ratio acceptable range (%TIR) during the first 28 days following warfarin initiation, and %TIR and count of bleeding events over the entire follow-up period. Two hundred thirty-four participants were followed up to day 28 (NextDose: 116 and standard of care: 118), and 228 participants (114 per arm) were followed up to the final study visit. Median %TIR tended to be higher for participants receiving NextDose guided warfarin management during the first 28 days (63 vs. 56%, P = 0.13) and over the entire follow-up period (74 vs. 71%, P = 0.04). The hazard of clinically relevant minor bleeding events was lower for participants in the NextDose arm (hazard ratio: 0.21, P = 0.041). In NextDose, there were 89.3% of proposed doses accepted by prescribers. NextDose guided dose management in cardiac surgery patients requiring warfarin was associated with an increase in %TIR across the full follow-up period and fewer hemorrhagic events. A theory-based, pharmacologically guided approach facilitates higher quality warfarin anticoagulation. An important practical benefit is a reduced requirement for clinical experience of warfarin management.

Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow Assay.

ABSTRACT: Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients who had percutaneous coronary intervention within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event. Secondary outcomes included VerifyNow platelet reactivity units (PRUs) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42%-45%), followed by NPO status (26%-28%) and MCS alone (22%-24%). The primary outcome of major adverse cardiovascular event occurred in 1 patient (1.1%). Of 92 patients, 77% had a P2Y12 level collected within 24 hours, and 89% of the cohort was able to achieve the goal P2Y12 PRU of <194. The median P2Y12 value within 24 hours of cangrelor initation was 115 PRU (40-168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients who received a drug-eluting stent in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

The contributors to dosage calculation ability and its applicability to nursing education: An integrative review.

Medication errors are a major patient safety issue and account for 1-2 million hospitalizations and between 100,000 and 200,000 deaths annually. Approximately 41 % of all medication errors are due to improper dose calculations. Studies have shown mean scores on the medication dosage calculation test for nursing students range from 35 to 71 %. Despite new technology created to aid in dosage calculations, the issue is still prevalent among nurses. It is critical that the elements contributing to the nurses' ability to complete dosage calculations be determined so that calculation curriculum in nursing schools can be updated to better prepare students for practice. An integrative review was completed using the databases of PubMed, CINAHL, and Embase to answer the research question: What contributors impact nurses' and nursing students' ability to complete dosage calculations? Four articles met the specified inclusion criteria and were used for this review. The three most common contributing themes among the review sample included mathematical medication calculation ability, medication calculation frequencies, and dosage calculation education. Results from this review can inform the issue of dosage calculations and highlight the need for further research regarding the medication administration competencies taught in undergraduate nursing studies.

The development and evaluation of dose-prediction tools for allopurinol therapy (Easy-Allo tools).

AIMS: Dose escalation at the initiation of allopurinol therapy can be protracted and resource intensive. Tools to predict the allopurinol doses required to achieve target serum urate concentrations would facilitate the implementation of more efficient dose-escalation strategies. The aim of this research was to develop and externally evaluate allopurinol dosing tools, one for use when the pre-urate-lowering therapy serum urate is known (Easy-Allo1) and one for when it is not known (Easy-Allo2). METHODS: A revised population pharmacokinetic-pharmacodynamic model was developed using data from 653 people with gout. Maintenance doses to achieve the serum urate target of <0.36 mmol L-1 in >80% of individuals were simulated and evaluated against external data. The predicted and observed allopurinol doses were compared using the mean prediction error (MPE) and root mean square error (RMSE). The proportion of Easy-Allo predicted doses within 100 mg of the observed was quantified. RESULTS: Allopurinol doses were predicted by total body weight, baseline urate, ethnicity and creatinine clearance. Easy-Allo1 produced unbiased and suitably precise dose predictions (MPE 2 mg day-1 95% confidence interval [CI] -13-17, RMSE 91%, 90% within 100 mg of the observed dose). Easy-Allo2 was positively biased by about 70 mg day-1 and slightly less precise (MPE 70 mg day-1 95% CI 52-88, RMSE 131%, 71% within 100 mg of the observed dose). CONCLUSIONS: The Easy-Allo tools provide a guide to the allopurinol maintenance dose requirement to achieve the serum urate target of <0.36 mmol L-1 and will aid in the development of novel dose-escalation strategies for allopurinol therapy.

Adherencia al tratamiento en paciente polimedicado con sistemas personalizados de dosificación (SPD) y su impacto en salud / Adherence to treatment in polymedicated patients using Monitored Dosage Systems (MDS) and their impact on health

Los Sistemas Personalizados de Dosificación (SPD) son una herramienta eficaz, segura y homologada para el reacondicionamiento de fármacos en farmacia comunitaria. Estos implican la revisión del uso del medicamento (RUM) y la colaboración con el médico de atención primaria (MAP). En el presente artículo se describe el caso de una paciente de 57 años intervenida de lumbociatalgia en 2021 y 2022, con dolor crónico mal controlado y aturdimiento derivado del olvido y/o duplicidad de las tomas. Durante la dispensación habitual se detectan estos problemas relacionados con el medicamento (PRM) y se deriva a la paciente al servicio SPD. Tras la implantación del mismo, la paciente mejora a nivel cognitivo, eliminando el aturdimiento y controlando el dolor, lo que supuso un aumento en su calidad de vida. En conclusión, se destaca la importancia de los diferentes servicios disponibles en la farmacia para mejorar la calidad de vida del paciente, la adherencia al tratamiento y la detección de PRM. (AU)

Monitored Dosage Systems (MDS) are an efficient, reliable and approved device for drug reconditioning in pharmacy. These systems imply a review on proper drug use and the collaboration between primary health care and pharmacists. The case study describes a female patient with a surgical intervention due to lumbosciatica in 2021 and 2022. Patient describes uncontrolled chronic pain and confusion related to improper drug use. During regular dispensing of her medication, these medicine-related problems (MRP) were detected and the patient was referred to the MDS service. After its implementation, the patient’s confusion was eliminated and pain management was achieved, increasing her quality of life. As a conclusion, the different health services provided by the pharmacy can improve a patient’s quality of life, treatment adherence and MRP detection. (AU)