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Objective: We aim to describe the population pharmacokinetics (PPK) of tacrolimus in Chinese pediatric patients under 4 years old after liver transplantation and to develop individualized tacrolimus dosing software. Methods: A total of 663 blood concentrations from 85 patients aged 4.57 months to 3.97 years were collected in this study. PPK analysis was performed using a nonlinear mixed effects modeling approach with the software, Phoenix. Using C#, an individualized tacrolimus dosing software was created. The software was then used to predict the concentrations of another ten pediatric liver transplantation patients to verify the accuracy of said software. The predictive error (PE) and the absolute predictive error (APE) for each predicted time point were computed. Results: A one-compartment model with first-order elimination best fitted the data. The apparent volume of distribution (V/F) and apparent clearance (CL/F) were 198.65 L and 2.41 L/h. Postoperative days (POD), total bilirubin (TBIL), and the use of voriconazole significantly influenced tacrolimus apparent clearance. The incorporation of an increasing number of actual blood drug concentrations into the prediction resulted in a decrease in both PE (72%, 17%, 7%) and APE (87%, 53%, 26%). Conclusions: A qualified PPK model of tacrolimus was developed in Chinese pediatric patients. The individualized tacrolimus dosing software could be used as a suitable tool for the personalization of tacrolimus dosing for pediatric patients after liver transplantation. [ABSTRACT FROM AUTHOR]

Purpose: To assess the pharmacokinetics and pharmacodynamics of linezolid in a retrospective cohort of hospitalized Chinese older patients. Methods: Patients > 60 years of age, who received intravenous linezolid (600 mg), were included. A population pharmacokinetics (PPK) model was established using nonlinear mixed-effects modeling. The predictive performance of the final model was assessed using goodness-of-fit plots, bootstrap analyses, and visual predictive checks. Monte Carlo simulations were used to evaluate the achievement of a pharmacodynamics target for the area under the serum concentration–time curve/minimum inhibitory concentration (AUC0–24/MIC). Results: A total of 210 samples were collected from 120 patients. A one-compartment PPK model with linear elimination best predicted the linezolid plasma concentrations. Linezolid clearance (CL) was 4.22 L h−1 and volume of distribution (Vd) was 45.80 L; serum uric acid (SUA) was a significant covariate of CL. Conclusion: The results of this study indicated that the standard dose was associated with a risk of overexposure in older patients, particularly those with high SUA values; these patients would benefit from a lower dose (300 mg every 12 h). [ABSTRACT FROM AUTHOR]

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight‐based loading doses of LEV with respect to established therapeutic target concentrations. Meta‐regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight‐based dosing) to achieve maximum (Cpeak) and 12‐h (C12h) plasma concentrations that exceed 12 mg/L. The meta‐regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight‐based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight‐based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing. [ABSTRACT FROM AUTHOR]

Recent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non‐linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model‐based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two‐compartment model with first‐order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) as a covariate on clearance reduced inter‐individual variability from 57.3% to 38.5% (P <.001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD‐EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L. [ABSTRACT FROM AUTHOR]

Background: New intensive care unit (ICU) nurses often experience stress because of concerns about potentially harming their patients in a work environment that demands the rapid development of several skills in a limited training period. Aim: This study aimed to investigate the prioritisation of educational needs within adult ICUs, focusing on how new nurses evaluate their current knowledge and perceive the most critical competencies. Study Design: A cross‐sectional study was conducted among a convenience sample of 102 new ICU nurses in general and tertiary hospitals in South Korea. Educational needs were assessed using a structured questionnaire for new ICU nurses. This study investigated educational needs using paired t‐tests, Borich's assessment model and the Locus for Focus model. Results: Only 48% of participants were satisfied with their education. The highest‐rated educational content included preparing to use a defibrillator (95% CI = 2.44–3.28, p <.001), administering emergency drugs for cardiopulmonary resuscitation (CPR) (95% CI = 2.09–2.91, p <.001), starting and maintaining continuous renal replacement therapy (95% CI = 1.50–2.42, p <.001), applying and maintaining a ventilator (95% CI = 1.42–2.08, p <.001), preparing for intubation (95% CI = 1.23–1.97, p <.001), reporting to the emergency team, preparing equipment for CPR (95% CI = 1.12–1.94, p <.001) and drug calculation (95% CI = 0.87–1.53, p <.001). Conclusions: These findings indicate that educational programmes for new ICU nurses should be developed considering the aforementioned priorities. Furthermore, nurse educators should adopt a practical and active instructional method to repeatedly clarify content, prioritising the improvement of knowledge and performance of new ICU nurses. Relevance to Clinical Practice: This study guides clinical educators and managers in focusing on areas where new ICU nurses need additional training. Effective nurse residency programmes tailored to the specific needs of new ICU nurses can enhance their confidence and ability to handle ICU nursing challenges. [ABSTRACT FROM AUTHOR]

Varying rates of complications have been reported for prehospital sedation with ketamine, and the relationship to dosing has not been studied on a large scale. We evaluated the association between prehospital ketamine dosing and rates of intubations and other adverse events in patients with behavioral emergencies. Using the 2018/2019 ESO public-use research datasets, we included all non-traumatic, adult behavioral and drug-related EMS encounters with ketamine administration. Based on consensus guidelines, we stratified patients into "above" and "at/below" the maximum dosing for sedation (2 mg/kg IV/IO or 5 mg/kg IM) using the highest single dose of ketamine given. We created propensity scores for matched subjects using 1:1 propensity score matching. Using logistic regression, we compared rates of intubation and other airway interventions, antipsychotic coadministration, improvement reported by EMS, hypoxia, hypotension, and cardiac arrest between the two groups. We included 2383 patients: 478 in the above and 1905 in the at/below dose group. Above-dose ketamine was associated with a higher rate of intubation or supraglottic airway placement (6.4% v 3.3%, OR 2.0, 95% CI 1.00–3.90). Other airway interventions were similar (40.0% v 40.0%, OR 1, 95% CI 0.80–1.30). The above-dose group also showed a higher rate of improvement noted by EMS clinicians (92.5% v 88.7%, OR 1.6, 95% CI 1.01–2.40). The rates of antipsychotic coadministration, hypoxia, hypotension, and cardiac arrest were similar between the cohorts. Patients given ketamine doses above consensus recommendations for sedation appeared more likely to receive prehospital intubation but not more likely to experience other adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Clinical decision support systems (CDSS) are used to identify drugs with potential need for dose modification in patients with renal impairment. ChatGPT holds the potential to be integrated in the electronic health record (EHR) system to give such dosing advices. In this study, we aim to evaluate the performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal impairment. Methods: This cross-sectional study was performed at Tergooi Medical Center, the Netherlands. CDSS alerts regarding renal dysfunction were collected from the electronic health record (EHR) during a 2-week period and were presented to ChatGPT and an expert panel. Alerts were presented with and without patient variables. To evaluate the performance, suggested medication interventions were compared. Results: In total, 172 CDDS alerts were generated for 80 patients. Indecisive responses by ChatGPT to alerts were excluded. For alerts presented without patient variables, ChatGPT provided "correct and identical" responses to 19.9%, "correct and different" responses to 26.7%, and "incorrect responses to 53.4% of the alerts. For alerts including patient variables, ChatGPT provided "correct and identical" responses to 16.7%, "correct and different" responses to 16.0%, and "incorrect responses to 67.3% of the alerts. Accuracy was better for newer drugs such as direct oral anticoagulants. Conclusion: The performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal dysfunction was poor. Based on these results, we conclude that ChatGPT, in its current state, is not appropriate for automatic integration into our EHR to handle CDSS alerts related to renal dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: In June 2020, modified‐release paracetamol (paracetamol‐MR) preparations were up‐scheduled from schedule‐2 (available in pharmacy) to schedule‐3 (available by request to a pharmacist only). The present study aims to ascertain whether up‐scheduling affected the frequency of paracetamol‐MR overdoses. Methods: This is a retrospective cohort study of two data sets from 1 June 2017 to 31 May 2022. Monash Health data were extracted using the diagnosis of paracetamol overdose coding and electronic medical records data. Calls regarding paracetamol‐MR overdoses to Victorian Poisons Information Centre (VPIC) were extracted from the Poisons centre call database. We used a quasi‐experimental research design with interrupted time series analysis to evaluate the immediate impact and change in trend of poisoning‐related calls and ED presentations before and after June 2020. The change in proportion of paracetamol‐MR cases in both databases was analysed using the Χ2 test. Results: The proportion of paracetamol‐MR cases in both data sets did not change. From Monash Health, there was no level change in monthly paracetamol‐MR overdose‐related presentations following re‐scheduling (rate ratio [RR] = 1.08, 95% confidence interval [CI] = 0.57–2.01). There was no change in monthly paracetamol‐MR overdose‐related calls to VPIC following re‐scheduling (RR = 1.05, 95% CI = 0.96–1.14). Conclusion: The proportion of paracetamol‐MR overdoses did not decrease after the up‐scheduling to S3. Similarly, the frequency of overdoses by month remained similar. Further limitations on access to paracetamol products may need to be considered. [ABSTRACT FROM AUTHOR]

Tacrolimus metabolism is heavily influenced by the CYP3A5 genotype, which varies widely among African Americans (AA). We aimed to assess the performance of a published genotype‐informed tacrolimus dosing model in an independent set of adult AA kidney transplant (KTx) recipients. CYP3A5 genotypes were obtained for all AA KTx recipients (n = 232) from 2010 to 2019 who met inclusion criteria at a single transplant center in Philadelphia, Pennsylvania, USA. Medical record data were used to calculate predicted tacrolimus clearance using the published AA KTx dosing equation and two modified iterations. Observed and model‐predicted trough levels were compared at 3 days, 3 months, and 6 months post‐transplant. The mean prediction error at day 3 post‐transplant was 3.05 ng/mL, indicating that the model tended to overpredict the tacrolimus trough. This bias improved over time to 1.36 and 0.78 ng/mL at 3 and 6 months post‐transplant, respectively. Mean absolute prediction error—a marker of model precision—improved with time to 2.33 ng/mL at 6 months. Limiting genotype data in the model decreased bias and improved precision. The bias and precision of the published model improved over time and were comparable to studies in previous cohorts. The overprediction observed by the published model may represent overfitting to the initial cohort, possibly limiting generalizability. [ABSTRACT FROM AUTHOR]

Purpose: Vancomycin is commonly prescribed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, including patients with end stage renal disease (ESRD) receiving intermittent hemodialysis (IHD). Infection is the second-leading cause of mortality in this patient population; therefore, optimizing vancomycin dosing is essential. New guidelines recommend using the ratio of area under the curve (AUC)/minimal inhibitory concentration (MIC) dosing with a target of 400-600 to maximize efficacy and minimize vancomycin nephrotoxicity. Summary: A retrospective chart review was performed to assess the current protocol for vancomycin dosing in ESRD patients on IHD at a community hospital in North Mississippi. A protocol was developed for dosing vancomycin utilizing AUC/MIC targets in this patient population. The study included all inpatient adults with ESRD receiving IHD at least 3 times weekly and receiving vancomycin. Data collection occurred in two phases. The first phase of data collection occurred before implementation of the new protocol and assessed the current vancomycin protocol effectiveness. In phase II of data collection, an assessment of the newly developed protocol utilizing similar data collected in phase I was conducted. Conclusions: It is thought that the difference in treatment outcomes and AUC/MIC targets is due to decreased immune function in this population. For this reason, we set our goal pre-dialysis level at 20-25 mg/dL, rather than 17-25 mg/dL, which correlates with an AUC/MIC of 480-600. It is important to quickly achieve therapeutic levels for the patients that do have MRSA to improve outcomes, to sustain these levels, and to reduce adverse events and costs. [ABSTRACT FROM AUTHOR]

Background: Medication dosing in overweight and obese children often involves complex weight-based calculations, leading to higher dosing errors, particularly with intravenous drugs. Currently, tools to aid in dosage calculations are lacking for these patients, especially in Thai population. Objective : This study aimed to develop a mobile application with the intent of utilizing it as a tool to enhance the efficiency and accuracy of dosing calculations required for obese and overweight Thai children. Methods: The performance of the application was assessed in 3 key aspects using a sample of 30 healthcare professionals. These key aspects included: 1) the accuracy of dosage calculations, assessed through pre- and posttests comparing manual calculations to app-based calculations using a 10-item questionnaire, 2) the time taken for calculations before and after app usage, 3) user satisfaction, which was measured through a questionnaire. Results: The integration of applications into the calculation demonstrated a significant improvement when compared to the manual calculation in both accuracy (6.10 vs 9.33 out of 10, P <.001) and efficiency (10.40 vs 8.53 minutes per 10 questions, P =.008). Also, the application elicited high levels of satisfaction among users, as reflected by an overall mean satisfaction score of 4.57 on a 5-point scale. Conclusion : The integration of this application to assist in dosage calculations for overweight and obese pediatric Thai patients has yielded favorable outcomes concerning accuracy, efficiency, and user satisfaction. Further development should be pursued within a larger cohort, with an emphasis on real-world implementation in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. Methods: We utilized the linear‐quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal‐tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early‐stage lung cancer. Mean lung BED, Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed‐rank test. Results: The transition point occurs when the tumor‐to‐normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose‐volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). Conclusions: The hyperfractionated regimen has an advantage in the high‐dose region of the lung but a disadvantage in the low‐dose region. Further research is needed to determine the superiority between hypo‐ and hyperfractionation. [ABSTRACT FROM AUTHOR]

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Introduction Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. Methods Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). Results Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. Conclusions The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions are common in children. Risk factors predisposing to IgE-mediated drug allergies and delayed drug reactions are a matter of debate. Gender, age, previous reactions to the same drug or to another drug, reduced drug metabolism, chronic diseases, polypharmacy, drug doses are linked with the onset of hypersensitivity reactions in some children. Novel advances in genetic polymorphisms can rapidly change the approach to the prevention of reactions since gene testing can be a useful screening test for severe cutaneous adverse reactions. Viral infections may act as cofactors in susceptible individuals. Polypharmacy, high doses, repeated doses and parental route of administration are also risk factors. Clinicians should take into account risk factors to allow the risk–benefit balance to be maintained. [ABSTRACT FROM AUTHOR]

Background: Medicinal plant-mediated combinational therapies have gained importance globally due to minimal side effects and enhanced treatment outcomes compared to single-drug modalities. We aimed to analyze the cytotoxic potential of each conventional treatment i.e., photodynamic therapy (PDT), chemotherapy (doxorubicin hydrochloride; Dox-HCl) with or without various concentrations of medicinal plant extracts (PE) on soft tissue cancer Rhabdomyosarcoma (RD) cell line. Methods: The Rhabdomyosarcoma (RD) cell line was cultured and treated with Photosensitizer (Photosense (AlPc4)), Chemo (Dox-HCl), and their combinations with different concentrations of each plant extract i.e., Thuja occidentalis, Moringa oleifera, Solanum surattense. For the source of illumination, a Diode laser (λ = 630 nm ± 1 nm, Pmax = 1.5 mW) was used. Photosensitizer uptake time (∼ 45 min) was optimized through spectrophotometric measurements (absorption spectroscopy). Drug response of each treatment arm was assessed post 24 h of administration using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5- 5-diphenyl-2 H- tetrazolium bromide (MTT) assay. Results: PE-mediated Chemo-Photodynamic therapy (PDT) exhibited synergistic effects (CI < 1). Moreover, Rhabdomyosarcoma culture pretreated with various plant extracts for 24 h exhibited significant inhibition of cell viability however most effective outcomes were shown by low and high doses of Moringa oleifera compared to other plant extracts. Post low doses treated culture with all plant extracts followed by PDT came up with more effectiveness when compared to all di-therapy treatments. Conclusion: The general outcome of this work shows that the ethanolic plant extracts (higher doses) promote the death of cancerous cells in a dose-dependent way and combining Dox-HCl and photo-mediated photodynamic therapy can yield better therapeutic outcomes. [ABSTRACT FROM AUTHOR]

The application of model‐informed drug development (MIDD) has revolutionized drug development and regulatory decision making, transforming the process into one that is more efficient, effective, and patient centered. A critical application of MIDD is to facilitate dose selection and optimization, which play a pivotal role in improving efficacy, safety, and tolerability profiles of a candidate drug. With the surge of interest in small interfering RNA (siRNA) drugs as a promising class of therapeutics, their applications in various disease areas have been extensively studied preclinically. However, dosing selection and optimization experience for siRNA in humans is limited. Unique challenges exist for the dose evaluation of siRNA due to the temporal discordance between pharmacokinetic and pharmacodynamic profiles, as well as limited available clinical experience and considerable interindividual variability. This review highlights the pivotal role of MIDD in facilitating dose selection and optimization for siRNA therapeutics. Based on past experiences with approved siRNA products, MIDD has demonstrated its ability to aid in dose selection for clinical trials and enabling optimal dosing for the general patient population. In addition, MIDD presents an opportunity for dose individualization based on patient characteristics, enhancing the precision and effectiveness of siRNA therapeutics. In conclusion, the integration of MIDD offers substantial advantages in navigating the complex challenges of dose selection and optimization in siRNA drug development, which in turn accelerates the development process, supports regulatory decision making, and ultimately improves the clinical outcomes of siRNA‐based therapies, fostering advancements in precision medicine across a diverse range of diseases. [ABSTRACT FROM AUTHOR]

This article describes a program through which interactions every 2–3 weeks between patients and primary care clinicians (PCCs), with recommendations based on analysis of remote glucose monitoring by computerized insulin dose adjustment algorithms, significantly improved diabetes control. Insulin doses increased by 30% in the majority of patients. A sizeable minority (36%) had a decrease or no increase in insulin doses, but still showed an improvement in diabetes control. Frequent interactions allowed PCCs the opportunity to recognize and address medication nonadherence. [ABSTRACT FROM AUTHOR]

Accurate dose delivery is crucial for cervical cancer volumetric modulated arc therapy (VMAT). We aimed to develop a robust deep-learning (DL) algorithm for fast and accurate dose prediction of cervical cancer VMAT in multicenter datasets and then explore the feasibility of the DL algorithm to endometrial cancer VMAT with different prescriptions. We proposed the AtTranNet algorithm for three-dimensional dose prediction. A total of 367 cervical patients were enrolled in this study. Three hundred twenty-two cervical patients from 3 centers were randomly divided into 70%, 10%, and 20% as training, validation, and testing sets, respectively. Forty-five cervical patients from another center were selected for external testing. Moreover, 70 patients of endometrial cancer with different prescriptions were further selected to test the model. Prediction precision was evaluated by dosimetric difference, dose map, and dose-volume histogram metrics. The prediction results were all clinically acceptable. The mean absolute error within the body in internal testing was 0.66 ± 0.63%. The maximum |δD| for planning target volume was observed in D98, which is 1.24 ± 2.73 Gy. The maximum |δD| for organs at risk was observed in Dmean of bladder, which is 4.79 ± 3.14 Gy. The maximum |δV| were observed in V40 of pelvic bones, which is 4.77 ± 4.48%. AtTranNet showed the feasibility and reasonable accuracy in the dose prediction for cervical cancer in multiple centers. The model can also be generalized for endometrial cancer with different prescriptions without any transfer learning. • Proposed state-of-the-art model to predict the radiotherapy dose intelligently. • Automatic prediction results were stable across medical centers. • Computer-aided dose prediction can accelerate treatment planning. • The model also showed good generalizability for endometrial cancer. [ABSTRACT FROM AUTHOR]

Co-trimoxazole is a combination of two antimicrobial drugs, (trimethoprim and sulfamethoxazole), that are used to treat a wide variety of infections such as urinary tract infection, pneumocystis pneumonia and traveler's diarrhea. Hyperkalemia is a life-threatening electrolyte disturbance. Objectives: This study aimed to determine the incidence of hyperkalemia and its risk factors among hospitalized patients receiving intravenous co-trimoxazole at Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. Methods: This retrospective observational study included patients that were prescribed intravenous co-trimoxazole and identified using a computerized pharmacy system between January 2010 and December 2020. Patients' demographic and clinical characteristics were retrieved from their electronic medical records. The data were analyzed using descriptive and inferential statistical tests. Results: A total of 420 patients participated in this study. The median age of the patients was 51 (35-65) years and 55.5% were male. Hyperkalemia associated with co-trimoxazole was observed in (40.2%) of the patients. Around (44.2%) of patients who experienced hyperkalemia received a high dose of co-trimoxazole (15-20 mg/kg). Hyperkalemia occurred after the 5th day of co-trimoxazole treatment. Logistic regression analysis showed no relationship between hyperkalemia and age (adjusted odds ratio (AOR) 1.054, p=0.84), sex (AOR 1.167; p=0.471), dose (AOR 0.779; p=0.251), or use of concomitant medications (angiotensin-converting inhibitors, AOR 1.054, p=0.84; angiotensin receptor blockers, AOR 0.564; p=0.734; β-blockers, AOR 0.986; p=0.963; potassium supplements, AOR 0.59; p=0.175; nonsteroidal anti-inflammatory drugs, AOR 0.842, p=0.684; spironolactone AOR 0.748, p=0.629; heparin AOR 0.822, p=0.382; calcineurin inhibitor, AOR 1.537, p=0.406). Conclusion: Co-trimoxazole use was associated with a high incidence of hyperkalemia in this group of patients. No association between hyperkalemia and risk factors was observed. Serum potassium levels should be closely monitored, especially in the first week of co-trimoxazole treatment, to prevent the incidence of hyperkalemia, and clinical staff should adhere to serum monitoring guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Personalised dosimetry based on molecular imaging is a field that has grown exponentially in the last decade due to the increasing success of Radioligand Therapy (RLT). Despite advances in imaging-based 3D dose estimation, the administered dose of a therapeutic radiopharmaceutical for RLT is often nonpersonalised, with standardised dose regimens administered every 4–6 weeks. Biodosimetry markers, such as chromosomal aberrations, could be used alongside image-based dosimetry as a tool for individualised dose estimation to further understand normal tissue toxicity and refine the administered dose. In this review we give an overview of biodosimetry markers that are used for blood dose estimation, followed by an overview of their current results when applied in RLT patients. Finally, an in-depth discussion will provide a perspective on the potential for the use of biodosimetry in the nuclear medicine clinic. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis aimed to determine whether apical patency increases postoperative pain after endodontic therapy. This study explored the degree and incidence of postoperative pain during root canal therapy, as well as the number of required analgesic doses. We searched PubMed, Scopus, Embase, Web of Science, Cochrane Library, and gray literature from the date of database inception until May 2023. RevMan 5.4 software was used for data analysis. Twelve studies were considered eligible for meta‐analysis. The mean pain scores on days 1 (mean difference [MD] = ‐1.69) and 2 (MD = ‐0.85) differed significantly between the apical patency and non‐patency groups. The odds for pain after 24 h were significantly lower (OR 0.59) in the apical patency group than in the non‐patency group. Furthermore, the mean number of required analgesic doses was not significantly different between the two groups. In conclusion, apical patency significantly alleviated postoperative pain (low‐quality evidence) and reduced the incidence of pain (moderate evidence). However, high‐quality randomized controlled trials are required to validate these findings. [ABSTRACT FROM AUTHOR]

Introduction: Rapidly increasing costs of medication acquisition can pose a challenge for health-system pharmacy budgets. The impact of dose-rounding in a pediatric oncology population has not previously been well documented and a retrospective review was undertaken to quantify the potential cost benefits. Methods: A retrospective chart review of patients with an oncologic diagnosis was performed for cytotoxic agents, asparaginase products, and biotherapy administered between January 1, 2014, and December 31, 2017. In the analysis, orders that could be rounded down to the nearest vial size by 5 or 10% were included. Medication pricing information was based on wholesale acquisition cost (WAC) and was provided by the Department of Pharmacy. Cost savings per medication were determined by multiplying the WAC of the medication by the number of vials saved. Results: Over a 4-year span, 347 patients were evaluated and 552 out of a possible 3110 orders (17.7%) met criteria for a theoretical cost savings of approximately $1,126,000 (∼$3200 per patient). Rounding down doses by up to 5% resulted in a potential savings of about $529,000. When rounding was extended to 5–10% of the originally ordered dose, an additional $597,000 of approximate cost savings could have been realized. The medications with the largest impact on cost savings were rituximab, pegaspargase, and erwinia asparaginase. Conclusions: For pediatric oncology patients, there exists a unique potential cost savings opportunity if doses are rounded down within 5 or 10% of the originally ordered weight-based or body surface area-calculated dose. [ABSTRACT FROM AUTHOR]

Background: Anticonvulsant prophylaxis (ACP) for early post-traumatic seizures (PTS) is recommended in patients with traumatic brain injury (TBI). Phenobarbital (PB) may be used to prevent alcohol withdrawal syndrome (AWS) in at-risk patients. The dual-purpose use of PB in the TBI population would allow for consolidation of pharmacotherapy. Objective: The primary objective of this study was to determine the frequency of early PTS in TBI patients at risk of AWS treated with PB as ACP. Secondary objectives included determining rates of over sedation and endotracheal intubation. Methods: Patients received an intravenous (IV) loading dose of PB at 15-20 mg/kg followed by 1 mg/kg every 12 hours for 7 days with a goal level of 15-20 mcg/mL. Medication data, seizure frequency, and episodes of over sedation and endotracheal intubation were collected. Results: Eighty patients were treated with PB over a 1-year period. Thirty-nine patients were analyzed. Median loading dose was 19.9 (Interquartile Range 19.1-20.0) mg/kg with a median post load level of 21.7 mcg/mL (IQR 18.3-25.8) mcg/mL. One patient (2.6%) had electrographic evidence for early PTS. PB was discontinued in 4 (10.3%) patients out of concern for over sedation. One patient required endotracheal intubation after rapid PB loading. Conclusion: The frequency of early PTS was low when PB was used as primary ACP in patients with TBI at risk for AWS. Over sedation is a potential adverse effect that should be considered in the choice of ACP. No conclusions can be drawn as to the effectiveness of PB in preventing AWS. [ABSTRACT FROM AUTHOR]

Introduction: Initiating favipiravir in COVID-19 patients with long-term warfarin use can lead to increased INR. However, data on the onset and duration of the increasing INR are limited. Method: We reviewed patient charts to include COVID-19 adult patients who received favipiravir for at least 5 days and used warfarin at the same dose for at least 12 weeks. Data on demographics, comorbidities, other medical characteristics, international normalized ratio (INR), and signs of bleeding were collected. Result: Eight patients, with a mean age of 70.88 ± 8.49 years old, received the standard dose of favipiravir. The mean maximum INR (4.30 ± 1.26) was statistically different from the baseline INR (P =.00029) and the change was observed within 4.38 ± 1.99 days after initiating favipiravir. Warfarin was then discontinued without favipiravir discontinuation in most patients, allowing the INR to gradually decrease within 2 to 3 days. Conclusion: Concurrent use of favipiravir and warfarin led to INR prolongation within approximately 4 days. The effect of such interaction can be acute as the prolongation occurred within 1 day in 1 of the patients. [ABSTRACT FROM AUTHOR]

Purpose This project aimed to determine whether a supportive calculator that automates the vial selection process might offer a practical and efficient method of reducing pharmaceutical expenditures through minimizing preventable drug waste in outpatient pharmacy settings. Summary Drug waste is a substantial target of cost-saving efforts in the areas of oncology and autoimmune therapy, which involve use of a vast number of high-cost medications packaged in single-dose vials of varying strength. To facilitate selection of the optimal combination of medication vials and thereby minimize preventable drug waste, a Microsoft Excel–based calculator was developed for use by staff of a large oncology pharmacy network. Twenty-three high-cost chemotherapy and monoclonal antibody medications were identified as initial targets for the drug waste prevention initiative. After dissemination and implementation of the calculator and provision of monthly pharmacy staff education, the dollar value of preventable drug waste and the number of suboptimal vial combination selections were reduced by 51% ($412,300) and 54% (315 selections), respectively, in fiscal year 2022 and further reduced by 46% ($183,400) and 27% (71 selections), respectively, in fiscal year 2023. Conclusion After implementation of an automated vial selection tool, preventable drug waste and the quantity of suboptimal vial combination selections were markedly reduced across 11 outpatient compounding pharmacies. [ABSTRACT FROM AUTHOR]

Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN). Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BED ef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BED ef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models. An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BED ef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BED ef = 279 Gy) by the RSM and ANN models. The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime. • HDR-BT is an effective therapy modality for patients with localised prostate carcinoma. • Optimisation of HDR-BT regime variables was carried out by the RSM and ANN models. • The RSM and ANN models determined almost the same optimal values. [ABSTRACT FROM AUTHOR]

Purpose: We present the case of a 67-year-old woman with severely reduced renal clearance suffering from ceftazidime-induced encephalopathy. Subsequently, we search the literature to review and describe the neurotoxicity of ceftazidime. Methods: A search string was developed to search PubMed for relevant cases from which relevant information was extracted. Using the collected data a ROC analysis was performed in R to determine a neurotoxicity threshold. Results: Our patient suffered from progressive loss of consciousness and myoclonic seizures, with improvements noted a few days after discontinuation of treatment. The dose was not appropriately reduced to take into account her reduced renal function. The highest ceftazidime concentration recorded was 234.9 mg/mL. Using the Naranjo score we found a probable relationship between our patient's encephalopathy and ceftazidime administration. In the literature we found a total of 32 similar cases, most of which also had some form of renal impairment. Using our collected data and ceftazidime concentrations provided in the literature, a ROC analysis provided a neurotoxicity threshold of 78 mg/L for ceftazidime neurotoxicity. Conclusion: Ceftazidime-related neurotoxicity is a known issue, especially in patients with severe renal impairment. Yet no concrete toxicity threshold has been reported so far. We propose the first toxicity threshold for ceftazidime of 78 mg/L. Future prospective studies are needed to validate and optimize the neurotoxicity threshold as upper limit for ceftazidime therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Prescribers often face the challenge of predicting creatinine clearance (CrCl) in elderly patients who are 65 years or older and have serum creatinine (SCr) concentrations below 1 mg/dL. Studies have shown that utilizing rounded SCr would underestimate CrCl in this population, which could lead to the under-dosing of some medications like vancomycin. The current study aimed to compare the accuracy of vancomycin dosing using actual SCr versus rounded SCr to 1 mg/dL in elderly patients. A total of 245 patients were included. The therapeutic trough level (10–20 mg/L) was achieved in 138 (56.3%) patients using actual SCr. Sub-therapeutic (<10 mg/L) and supra-therapeutic (>20 mg/L) trough levels were observed in 32 (13.1%) and 75 (30.6%) patients, respectively. The predictive performance of different vancomycin doses based on actual SCr and rounded SCr compared to the targeted maintenance dose (TMD) showed a stronger correlation of dosing based on actual SCr with TMD (r = 0.55 vs. 0.31) compared to rounded SCr dosing; both doses showed similar precision, with ranges of ±552 mg/day for the dosing based on actual SCr and ±691 mg/day for the dosing based on rounded SCr. Furthermore, the dosing based on actual SCr showed a lower error percentage (69%) and a higher accuracy rate (57.6%) within ±10% of the TMD compared to the dosing based on rounded SCr, which had an error percentage of (92.3%) and an accuracy rate of (40%). The prevalence of vancomycin-associated nephrotoxicity (VAN) was seen in 44 (18%) patients. Patients between 75 and 84 years of age, those who were bedridden, and those with vancomycin trough concentrations greater than 20 mg/L had a higher risk of developing VAN. In conclusion, in elderly patients, estimating vancomycin dosing based on actual SCr was more accurate compared to rounded SCr to 1 mg/dL. The efficacy of vancomycin could be negatively affected by rounding up SCr, which could underestimate CrCl and result in the under-dosing of vancomycin. [ABSTRACT FROM AUTHOR]

Aims and background: The efficacy of dexmedetomidine and propofol in preventing postoperative delirium is controversial. This study aims to evaluate the efficacy of dexmedetomidine and propofol for preventing postoperative delirium in extubated elderly patients undergoing hip fracture surgery. Materials and methods: This randomized controlled trial included participants undergoing hip fracture surgery. Participants were randomly assigned to receive dexmedetomidine, propofol, or placebo intravenously during intensive care unit (ICU) admission (8 p.m. to 6 a.m.). The drug dosages were adjusted to achieve the Richmond Agitation Sedation Scale (RASS) of 0 to -1. The primary outcome was postoperative delirium. The secondary outcomes were postoperative complications, fentanyl consumption, and length of hospital stay. Results: 108 participants were enrolled (n = 36 per group). Postoperative delirium incidences were 8.3%, 22.2%, and 5.6% in the dexmedetomidine, propofol, and placebo groups, respectively. The hazard ratios of dexmedetomidine and propofol compared with placebo were 1.49 (95% CI, 0.25, 8.95; p = 0.66) and 4.18 (95% CI, 0.88, 19.69; p = 0.07). The incidence of bradycardia was higher in the dexmedetomidine group compared with others (13.9%; p = 0.01) but not for hypotension (8.3%; p = 0.32). The median length of hospital stays (8 days, IQR: 7, 11) and fentanyl consumption (240 µg, IQR: 120, 400) were not different among groups. Conclusion: This study did not successfully demonstrate the impact of nocturnal low-dose dexmedetomidine and propofol in preventing postoperative delirium among elderly patients undergoing hip fracture surgery. While not statistically significant, it is noteworthy that propofol exhibited a comparatively higher delirium rate. [ABSTRACT FROM AUTHOR]

PF‐06817024 is a high affinity, humanized antibody that binds interleukin‐33, a proinflammatory type 2 cytokine, and thereby has the potential to inhibit downstream type 2 inflammation. This Phase 1, randomized, placebo‐controlled study was conducted in 3 parts to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics of escalating single and limited repeat PF‐06817024 doses in healthy participants (Part 1), a single dose of PF‐06817024 in participants with chronic rhinosinusitis with nasal polyps (Part 2), and repeat doses of PF‐06817024 in participants with moderate to severe atopic dermatitis (atoptic dermatitis; Part 3). PF‐06817024 was generally well tolerated in all participant populations. Most participants experienced a treatment‐emergent adverse event (healthy participants, 78.4% and 100%; participants with chronic rhinosinusitis with nasal polyps, 90.9% and 88.9%; and participants with atoptic dermatitis, 60.0% and 62.5% in the PF‐06817024 and placebo groups, respectively). No substantial deviations from dose proportionality were observed for single intravenous doses of 10‐1000 mg, indicating linear PK in healthy participants. Mean terminal half‐life ranged from 83 to 94 days after single intravenous administration in healthy participants and was similar to that observed after administration in the studied patient populations. Incidences of antidrug antibodies in the studied populations were 10.8%, 9.1%, and 5.0% for healthy participants, participants with chronic rhinosinusitis with nasal polyps, and participants with atoptic dermatitis, respectively. In addition, dose‐dependent increases were observed in total serum interleukin‐33 levels of treated participants, indicating target engagement. Overall, the PK and safety profile of PF‐06817024 supports further investigation of the drug as a potential treatment for allergic diseases. [ABSTRACT FROM AUTHOR]

Context Vitamin D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive. Objective The aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400 IU) in preventing infections in apparently healthy children < 5 years of age. Data Sources PubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria. Data Extraction Meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at > 400 IU compared with placebo, no treatment, or standard dose were included. Data Analysis Seven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62–1.10). There was a 57% (95%CI, 0.30–0.61), 56% (95%CI, 0.27–0.07), and 59% (95%CI, 0.26–0.65) reduction in the odds of influenza/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D > 1000 IU. No effect was found on bronchitis, otitis media, diarrhea/gastroenteritis, primary care visits for infections, hospitalizations, or mortality. Conclusion High-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed. Systematic Review Registration PROSPERO registration number CRD42022355206. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To refresh your knowledge of the administration of intravenous (IV) fluids and medicines • To enhance your ability to identify and resolve issues that may occur with the administration of IV fluids and medicines • To contribute towards revalidation as part of your 35 hours of CPD (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers). Managing intravenous (IV) access is a standard proficiency for UK nurses, enabling them to administer IV injections and IV infusions and to manage injection equipment and infusion pumps and devices. In this article the author describes various types of venous access devices that are commonly seen in practice and details the preparation, checking and administration of IV fluids and medicines, including some complications that may arise. The author also discusses the calculation of fluid requirements, types of IV fluids, displacement values and ongoing care of venous access devices. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is a growing public health issue affecting one in seven adults in the UK and is associated with increased risk of cardiovascular disease and premature death [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the median effective dose (ED50) and 95% effective dose (ED95) of nicardipine for treating pituitrin-induced hypertension during laparoscopic myomectomy, providing guidance for the management of intraoperative blood pressure in such patients. Methods: Among the initial 40 participants assessed, 24 underwent elective laparoscopic myomectomy. A sequential up-and-down method was employed to ascertain the ED50 of nicardipine based on its antihypertensive efficacy. Nicardipine was initially administered at 6 µg/kg following the diagnosis of pituitrin-induced hypertension in the first patient. Dosing adjustments were made to achieve the desired antihypertensive effect, restoring systolic blood pressure and heart rate to within ± 20% of baseline within 120 s. The dosing increment or reduction was set at 0.5 µg/kg for effective or ineffective responses, respectively. The ED50 and ED95 of nicardipine were calculated using Probit regression by Maximum Likelihood Estimation (MLE) to establish dose-response curves and confidence intervals. Results: 24 patients were included for analysis finally. The ED50 and ED95 of nicardipine for blood pressure control after pituitrin injection were determined. The study found that the ED50 of nicardipine for treating pituitrin-induced hypertension was 4.839 µg/kg (95% CI: 4.569–5.099 µg/kg), and the ED95 was estimated at 5.308 µg/kg (95% CI: 5.065–6.496 µg/kg). Nicardipine effectively mitigated the hypertensive response caused by pituitrin without inducing significant tachycardia or hypotension. Conclusions: Nicardipine effectively controlled blood pressure after pituitrin injection during laparoscopic myomectomy, with ED50 and ED95 values established. This research highlights the potential utility of nicardipine in addressing hypertensive responses induced by pituitrin, particularly in clinical settings where pituitrin is routinely administered. [ABSTRACT FROM AUTHOR]

Wrong dose calculation medication errors are widespread in pediatric patients mainly due to weight-based dosing. PediPain app is a clinical decision support tool that provides weight- and age- based dosages for various analgesics. We hypothesized that the use of a clinical decision support tool, the PediPain app versus pocket calculators for calculating pain medication dosages in children reduces the incidence of wrong dosage calculations and shortens the time taken for calculations. The study was a randomised controlled trial comparing the PediPain app vs. pocket calculator for performing eight weight-based calculations for opioids and other analgesics. Participants were healthcare providers routinely administering opioids and other analgesics in their practice. The primary outcome was the incidence of wrong dose calculations. Secondary outcomes were the incidence of wrong dose calculations in simple versus complex calculations; time taken to complete calculations; the occurrence of tenfold; hundredfold errors; and wrong-key presses. A total of 140 residents, fellows and nurses were recruited between June 2018 and November 2019; 70 participants were randomized to control group (pocket calculator) and 70 to the intervention group (PediPain App). After randomization two participants assigned to PediPain group completed the simulation in the control group by mistake. Analysis was by intention-to-treat (PediPain app = 68 participants, pocket calculator = 72 participants). The overall incidence of wrong dose calculation was 178/576 (30.9%) for the control and 23/544 (4.23%) for PediPain App, P < 0·001. The risk difference was − 32.8% [-38.7%, -26.9%] for complex and − 20.5% [-26.3%, -14.8%] for simple calculations. Calculations took longer within control group (median of 69 Sects. [50, 96]) compared to PediPain app group, (median 48 Sects. [38, 63]), P < 0.001. There were no differences in other secondary outcomes. A weight-based clinical decision support tool, the PediPain app reduced the incidence of wrong doses calculation. Clinical decision support tools calculating medications may be valuable instruments for reducing medication errors, especially in the pediatric population. Key Points: Question: Can a clinical decision support tool app decrease opioids and pain medications' wrong dose calculations errors in the pediatric patients compared to a calculator and reference book?. Findings: A weight-based clinical decision support tool, the PediPain app, reduced the incidence of wrong doses calculations compared to the use of a calculator and reference handbook. Meaning: Our study demonstrates the potential for favorable clinical outcomes that clinical decision support tools could bring to the medical field, especially for clinical situations with a high cognitive workload. [ABSTRACT FROM AUTHOR]

Simple Summary: While stereotactic body radiation therapy (SBRT) has become increasingly used for the treatment of non-metastatic prostate cancer since its insurance coverage in Japan in 2016, optimal dose fractionation remains undetermined. This study was a phase 1 dose escalation trial of SBRT, aiming to assess the maximum tolerated dose (MTD) of SBRT using five fractions. Patients were planned to receive SBRT at doses of 42.5, 45, or 47.5 Gy, with toxicity as the primary endpoint. No dose-limiting toxicities were observed at 42.5 Gy, and one patient experienced a grade 4 rectal perforation at 45 Gy, leading to the determination of 42.5 Gy as the MTD. There were no deaths or biochemical recurrences during the follow-up period. This study underscores the need for further trials to ascertain the optimal SBRT dose fractionation, balancing efficacy and safety for non-metastatic prostate cancer treatment. The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph nodes or distant metastases were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion, and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in five fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity. [ABSTRACT FROM AUTHOR]

Background: Medication dosing calculation errors can cause significant harm to patients, especially in the pediatric population. Crushing tablets for dose division purposes may increase the risk of calculation errors, which can lead to incorrect dosing and compromised patient safety. This study aimed to develop a calculator to eliminate calculation errors associated with dose division. Methods: Using the Wix platform, a group of pharmacists created a user-friendly webpage "Dose 4 You." To enable accurate dose division calculations, the advanced language model Chat GPT and Visual Studio were used. The tool assists healthcare professionals through a step-by-step process, allowing them to enter the necessary dose and medication requirements. The Dose 4 You web page's reliability and feasibility were assessed using retrospective data and validated questionnaires, including the System Usability Scale (SUS), respectively and a Likert scale-based acceptance questionnaire. Results: The Dose 4 You website calculated the required amount of powdered tablet to achieve the desired dose with 100% accuracy. The obtained SUS score was 88.38, indicating excellent usability. The average score of all questions for acceptance was found to be 4.7 ± 0.15 indicating a strong agreement on the tool's usefulness and effectiveness. Conclusion: Dose 4 You is a reliable tool that improves patient safety by streamlining dose calculations and lowering calculation errors. The tool's ease of use, practicality in daily clinical practice, and potential to reduce medication errors are highlighted by the positive perception among healthcare professionals. Dose 4 You's successful implementation demonstrates the power of technology and collaboration in transforming medication administration and improving patient outcomes. Similar innovative solutions to optimize healthcare practices can be explored in future health informatics endeavors. [ABSTRACT FROM AUTHOR]

Prehospital rapid sequence intubation (RSD, like inpatient RSI, is not without risk of adverse effects to the patient. The most notable of these adverse effects is postintubation hemodynamic instability. Air medical providers choose induction agents for critically ill patients who require emergent airway management, some of whom may already be hemodynamically unstable prior to RSI. Ketamine is often selected as the induction agent of choice for patients who are either unstable before RSI or have a high index of suspicion of becoming unstable in the postintubation period. Although widely considered to have a good safety profile for induction, ketamine administration has been correlated with episodes of postintubation hypotension. In this retrospective literature review, the effect of using half-dose ketamine for induction in patients who show pre-RSI instability (systolic blood pressure <90 mm Hg or body mass index >30) on postintubation hemodynamics is examined. [ABSTRACT FROM AUTHOR]

Background: Patients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations. Aim: To determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care. Method: The Cockcroft–Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland–Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison. Results: A total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations. Conclusion: Clinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the effective integration of pharmacometrics and pharmacovigilance in managing medication errors, highlighted by a case involving secukinumab in a patient with hidradenitis suppurativa. Methods: We present the case of a 41-year-old male with progressive hidradenitis suppurativa, unresponsive to multiple antibiotic regimens and infliximab treatment. Due to a medication error, the patient received 300 mg of secukinumab daily for 4 days instead of weekly, totaling 1200 mg. The regional pharmacovigilance center assessed potential toxicity, and a pharmacometric analysis using a population pharmacokinetic model was performed to inform dosing adjustments. Results: Clinical data indicated that the received doses were within a non-toxic range. No adverse effects were observed. Pharmacometric simulations revealed a risk of underexposure due to the dosing error. Based on these simulations, it was recommended to restart monthly secukinumab injections on day 35 after the initial dose. Measured plasma concentrations before re-administration confirmed the model's accuracy. Conclusion: This case highlights the crucial collaboration between clinical services, pharmacovigilance, and pharmacometrics in managing medication errors. Such interdisciplinary efforts ensure therapeutic efficacy and patient safety by maintaining appropriate drug exposure levels. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in North America, with a survival rate of 85%. Despite improved outcomes, many survivors experience long-term side effects, including cognitive issues. This study investigates whether a brain imaging technique called Magnetization Transfer Ratio (MTR) can detect changes in the brain's white matter of ALL survivors and if these changes are related to cognitive problems. Lower MTR levels in survivors, indicating myelin damage, correlated with cognitive impairments. Additionally, a link between MTR levels and the doses of certain chemotherapy drugs received was discovered. These findings improve our understanding of ALL survivorship and highlight the importance of MTR in monitoring brain health during and after cancer treatment. Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments. Secondly, it examines the dose-related effects of chemotherapy agents on the MTR and its relationship to other risk factors such as female sex, early age diagnosis, and cranial radiotherapy. Magnetization transfer imaging was utilized to assess WM integrity in 35 survivors at a mean of 18.9 years after the onset of ALL (range since diagnosis: 6.9–26.8). Additionally, 21 controls matched for age, sex, and education level, with no history of cancer, were included. MTR was extracted from both the entire brain's WM and the corpus callosum through semi-automated procedures. The results indicated lower MTR means in survivors, which is linked to cognitive function. Negative associations between MTR means and intrathecal agents' (MTX, cytarabine, and hydrocortisone) cumulative doses received were highlighted. This study offers valuable insights into the connections between myelin deterioration, cognitive impairment, and the implications of IT chemotherapy, enhancing our understanding of ALL survivorship dynamics. It underscores MTR's relevance in monitoring neurotoxicity during oncological drug follow-up examinations. [ABSTRACT FROM AUTHOR]

This review evaluates the current evidence on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. All studies included in the review were conducted in Asia and the Middle East. Overall, the evidence suggests that SGLT2 inhibitors are a safe and effective treatment option for most T2DM patients fasting during Ramadan. The average incidence of symptomatic hypoglycemia is 12.5%, but ranges from 0.7% to 27%, depending on the study population and concomitant use of other medications. The risk of hypoglycemia is increased when SGLT2 inhibitors are used in combination with insulin and/or sulfonylureas. Therefore, patients taking SGLT2 inhibitors in combination with insulin and/or sulfonylureas can take steps to mitigate this risk, such as having their insulin and/or sulfonylurea doses adjusted and being closely monitored for hypoglycemia. Patients taking SGLT2 inhibitors may be at increased risk of dehydration. To mitigate the risk of dehydration, patients should be advised to consume adequate fluids during the fast-breaking hours. Further research is warranted to validate these findings and extend their applicability to high-risk populations and other regions of the world. Plain Language Summary: Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors on glycemic control in patients with type 2 diabetes mellitus fasting during Ramadan: a review This review delves into the existing evidence regarding the safety and efficacy of sodium-glucose co-transporter 2 (SGLT2) inhibitors for patients with type 2 diabetes mellitus (T2DM) who observe Ramadan fasting. The studies reviewed were conducted exclusively in Asia and the Middle East. Overall, the gathered evidence suggests that SGLT2 inhibitors constitute a safe and effective treatment option for most T2DM patients fasting during Ramadan. While a slightly elevated risk of dehydration compared to other medications may exist, this is generally well-tolerated. To mitigate the risk of dehydration, patients should be advised to consume adequate fluids during the fast-breaking hours. However, further research is warranted to validate these findings and extend their applicability to high-risk populations and other world regions. [ABSTRACT FROM AUTHOR]

Background: Drug desensitization allows for safe administration of a drug to a patient with a previous hypersensitivity reaction. Successful desensitization protocols have been described for different medications, including protocols for oncology patients. Few cases of desensitization to sorafenib and imatinib have been described in the literature so far. Objective: The objective of this paper is to describe the process of the sorafenib and imatinib drug hypersensitivity diagnosis and desensitization process in two patients. Methods: Two oncology patients who experienced non-immediate hypersensitivity reactions to sorafenib and imatinib underwent desensitization to these drugs. We designed a protocol for the first patient and used a modified protocol from the literature for the second patient. Results: By using a slow desensitization technique and gradual tapering of corticosteroids and antihistamines, both patients reached the target dose of the incriminated drug. Conclusions: Desensitization to sorafenib and imatinib can be an effective therapeutic option in patients with hypersensitivity to those medications, without alternative treatment options. [ABSTRACT FROM AUTHOR]

The role of clinical pharmacists or oncology pharmacists in pediatric oncology has been established as important in anticancer regimen review, dose calculation, recommendation, chemocounseling, identification of drug-related problems, its resolution, and, prevention and monitoring of adverse drug reactions within high-income countries. With several hospitals providing pediatric oncology services in Nepal, clinical pharmacist involvement in these hospitals is very poor. Upon reviewing the reputed organization and association focused on pediatric oncology pharmacy practice, it looks imperative for Nepal to initiate clinical pharmacy services which will further help in improving patient health outcomes. As such in this commentary, we try to accentuate the pediatric oncology services and pediatric pharmacy practice within Nepal and try to pinpoint the potential areas for clinical pharmacists to focus if they intend to provide services in pediatric oncology pharmacy practice. [ABSTRACT FROM AUTHOR]

Simple Summary: CPX-351 has been approved for the treatment of acute myeloid leukemia. Previous studies have indicated that dose adjustment is not warranted for patients with mild to moderate renal impairment. However, the effect of severe renal impairment on the use of CPX-351 has not been established. In this study, we evaluated CPX-351 in patients with normal renal function and in patients with moderate and severe renal impairment. We compared how CPX-351 moves through the body, as well as the safety of the drug, in these different patient groups. The results suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment. This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, n = 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment, n = 8), or <30 mL/min (Cohort 3, severe renal impairment, n = 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment. [ABSTRACT FROM AUTHOR]

Symptoms of nausea and vomiting are common in palliative care and hospice patients. One of the many classes of medications used for the treatment of nausea and vomiting is dopamine receptor antagonists which are particularly helpful for treating nausea mediated by the chemoreceptor trigger zone (CTZ) and impaired gastrointestinal function. While dopamine antagonists can be very effective treatments for nausea they should be used with caution as they carry the risk of QTc prolongation, have a FDA black box warning for tardive dyskinesia (TD), and increased risk of precipitating psychosis and death in patients with dementia. This review will cover haloperidol, olanzapine, prochlorperazine, and metoclopramide for treatment of nausea and vomiting including evidence of efficacy, pharmacokinetics, and pharmacodynamics to improve safe and effective utilization in clinical practice. This includes medication receptor site affinities at histaminic, muscarinic, serotonergic, and alpha-adrenergic receptors which can help providers anticipate potential adverse effects and risk of extrapyramidal symptoms (EPS), TD, and QTc prolongation. This review also includes considerations for dose adjustments based on renal function, hepatic function, and age. Understanding the pharmacology of dopamine antagonists can help providers choose the best treatment for control of nausea and vomiting and subsequently improve patients' quality of life. [ABSTRACT FROM AUTHOR]