Improper Dosing Research Articles

Safety Profiles Related to Dosing Errors of Rapid-Acting Insulin Analogs: A Comparative Analysis Using the EudraVigilance Database.

Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. RAIAs are expected to be associated with a higher number of dosing errors because of their rapid onset, short duration of action, and the need for frequent dosing, compared to other insulin analogs. There are three approved RAIAs on the market: insulin lispro (LIS), insulin aspart (ASP), and insulin glulisine (GLU). The aim of this study is to evaluate the real-world evidence on dosing errors reported for RAIAs in EudraVigilance (EV), an established pharmacovigilance database, in comparison to other insulin analogs and human insulins. A descriptive analysis and a disproportionality analysis were conducted. ASP and LIS were associated with high percentages of adverse drug reactions (ADRs) (22% and 17%, respectively), with over 70% of the reports involving serious ADRs. A higher frequency of cardiac and eye disorder ADRs was observed for LIS compared with ASP and GLU. GLU showed a higher frequency of ADRs in the skin and subcutaneous tissue disorders category. LIS dosing errors accounted for 5% of the total number of cases, while dosing errors for ASP and GLU were less than 3%. The most frequently reported dosing errors involved improper dosing (49%). Although there were fewer dosing errors of RAIAs in comparison to other insulins, the severity of the potential outcome highlights the importance of precise dosing and timing. Improved the monitoring and reporting of these dosing errors could enhance diabetes patient care. Additionally, smart medical devices could improve therapeutic outcomes.

Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff.

The Cytochrome P450s (CYPs) enzyme family metabolizes ∼80% of small molecule drugs. Variants in CYPs can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across CYPs is challenging. Even closely related CYPs like CYP2C9 and CYP2C19, which share 92% amino acid sequence identity, display distinct phenotypic properties. Using Variant Abundance by Massively Parallel sequencing (VAMP-seq), we measured the steady-state protein abundance of 7,660 single amino acid variants in CYP2C19 expressed in cultured human cells. Our findings confirmed critical positions and structural features essential for CYP function and revealed how variants at conserved positions influence abundance. We jointly analyzed 4,670 variants whose abundance was measured in both CYP2C19 and CYP2C9, finding that the homologs have different variant abundances in substrate recognition sites within the hydrophobic core. We also measured the abundance of all single and some multiple WT amino acid exchanges between CYP2C19 and CYP2C9. While most exchanges had no effect, substitutions in substrate recognition site 4 (SRS4) reduced abundance in CYP2C19. Double and triple mutants showed distinct interactions, highlighting a region that points to differing thermodynamic properties between the two homologs. These positions are known contributors to substrate specificity, suggesting an evolutionary tradeoff between stability and enzymatic function. Finally, we analyzed 368 previously unannotated human variants, finding that 43% had decreased abundance. By comparing variant effects between these homologs, we uncovered regions underlying their functional differences, advancing our understanding of this versatile family of enzymes.

Prescribing Errors in an Ambulatory Care Setting: Mitigating Risks in Outpatient Medication Orders, Cross-Sectional Review

ABSTRACT Introduction Prescribing errors (PEs) are the most common type of medication error, which may occur by prescribing the wrong medication, improper dose, dosage, and/or even prescribing a drug to the wrong patient. The present study aims to compile PEs that were generated in an ambulatory care setting at a tertiary-care hospital in Saudi Arabia. Methods A retrospective cross-sectional review was conducted for all reported PEs in ambulatory care clinics for 3 years. The potential hazardous outcomes of these PEs were classified according to the medication error index. Results A total of 897 records containing 1199 PEs were retrieved. More than a third of prescribers had frequently committed PEs—ranging from 2 to 39 times. The most encountered errors were prescribing incorrect doses, medication duplication, incorrect dosing frequency, and inappropriate duration (34.5%, 14.1%, 11.6%, and 9.8%, respectively). The most frequent mistakes were when prescribing antibiotics (22.9%) and drugs for cardiovascular conditions (18.5%). Most errors were of mild to moderate severity, mostly type-B near-miss errors and did not reach patients. Only two prescription events (0.17%) had severe consequences that required intervention to avoid any subsequent harm or damage. Conclusion The current investigation has revealed a substantial percentage of PEs, mostly in internal medicine and cardiology departments. Although PEs are undoubtedly not easy to avoid, monitoring and recognizing these inaccuracies is pivotal to preventing potential harm and promoting patient safety.

Evaluation of Proper Treatment Delivery and Time of Initiation of Treatment After Hospitalization by Nursing Staff in Kuwait Teaching Hospital Peshawar

Background: Medication errors are a pressing public health concern, leading to adverse outcomes and substantial healthcare costs. This study examines the incidence of drug administration errors, emphasizing the critical importance of timely treatment initiation. Delays in treatment pose significant risks to patient safety, highlighting the need for improved medication delivery protocols and enhanced patient care practices in hospitals. Methods: A prospective cross-sectional study in a Kuwait teaching hospital's paediatrics unit, involving 120 participants, utilized non-probability convenient sampling. Data collection from patient files and attendants utilized a specially designed form. Data was collected by observing one patient for 24 hours. Participants were instructed to retain medication vials. Permission was obtained from the department head, and oral informed consent was secured. No personal identifiers were recorded. Interventions included workshops and performance evaluations, leading to observed improvement. Data analysis was conducted using SPSS version 22. Results: Baseline data showed variations in dose administration across departments, with notable discrepancies in proper drug administration alignment with prescriptions. Treatment initiation delays were significant, and patient satisfaction was moderate. Post-intervention, improvements were observed in dose administration, although treatment initiation delays persisted. However, patient satisfaction notably increased following interventions. Conclusion: Our study highlighted several critical issues in medication administration, such as delays in treatment initiation, improper dose administration, and missed doses. Implementing training sessions and workshops for nursing staff will ensure the best practices and they can manage their responsibilities more effectively.

Medication Errors in Saudi Arabian Hospital Settings: A Systematic Review.

Background and Objectives: Medication errors significantly impact patient safety, potentially causing adverse drug events (ADEs), increasing morbidity and mortality and prolonging hospital stays. This systematic review aimed to identify common medication errors in Saudi hospitals, their contributing factors, and effective prevention strategies. Materials and Methods: Following PRISMA-P guidelines, a comprehensive review of the literature published after 2019 was conducted. Inclusion criteria focused on peer-reviewed articles in English addressing medication errors in Saudi hospitals. Exclusion criteria eliminated reviews, opinion pieces, and non-peer-reviewed sources. A narrative synthesis identified common themes, and a descriptive analysis organized the data. Results: Searches yielded 22 articles from Embase (n = 4), PubMed (n = 10), and Web of Science (n = 8). After removing duplicates and one review article, twelve studies remained. Hand-searching references added 16 more, totaling 28 articles. Of the 28 included studies, 20 (71.4%) reported the types of medication errors observed. Wrong dose and improper dose errors are among the most frequently reported across multiple studies, while prescribing errors remain consistently high, indicating a critical area for intervention. Although less frequent, omission errors still hold significance. Conclusions: This review emphasizes the importance of comprehensive, proactive approaches to preventing medication errors. Integrating evidence-based strategies, fostering a safety culture, and continuously monitoring and evaluating interventions can significantly enhance medication safety and improve patient outcomes in Saudi Arabian hospitals.

THE ANALYSIS STUDY OF EFFECTIVENESS AND SAFETY OF ORAL SILDENAFIL CITRATE FOR TREATMENT OF ERECTILE DYSFUNCTION : A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Erectile dysfunction (ED) is a medical condition affecting men's sexual performance and well-being. Sildenafil citrate, a specific inhibitor of phosphodiesterase type 5, is approved for treating ED. The efficacy and safety of oral sildenafil citrate in treating ED are crucial for successful treatment procedures. Understanding the relationship between the efficacy and safety of oral sildenafil citrate can help develop successful treatment procedures for ED patients. Methods: This systematic review adhered to the PRISMA 2020 guidelines and primarily examined entire English literature published between 2000 and 2024. Only editorials and review articles published in the same publication as the submission were accepted if they possessed a Digital Object Identifier (DOI). A variety of online platforms, including ScienceDirect, PubMed, and SagePub, were utilized to gather the relevant literature. Result: The study analyzed more than 2000 papers from reputable sources such as Science Direct, SagePub, and PubMed. After deciding to subject eight publications to additional inspection, a thorough evaluation of the entire body of literature was carried out. Conclusion: Sildenafil, a potent treatment for erectile dysfunction (ED), has been found to be effective in improving men's psychosocial aspects. It is an inhibitor of PDE5, a condition that affects men's emotional well-being. The study also found that the firmness of erections was linked to improvements in psychosocial aspects. Sildenafil can be used interchangeably with tablets, providing a convenient alternative for those with difficulty swallowing. However, follow-up for men with ED is often inadequate due to improper doses and lack of understanding.

მოსახლეობის მიერ ანტიბიოტიკების თვითნებურად მოხმარების შესწავლის შედეგები

The 20th century witnessed the dawn of the antibiotic revolution and now the world is facing the phenomenon of increasing resistance to antibiotics. In this paper, our goal is to reveal the negative consequences of the arbitrary use of antibiotics by the population and to show the existing reality through research based on the population of Georgia. Arbitrary use of antibiotics is of great importance in the development of resistance and the associated clinical and economic burden increases accordingly. Arbitrary use of antibiotics has been reported in the general population as well as in hospitals and medical facilities. Mostly marked as overuse and inappropriate appointment. Improper dosing regimen and duration of treatment were considered to be major factors associated with antibiotic resistance; The study of the arbitrary use of antibiotics has revealed the widespread use of antibiotics without medical prescription or medical consultation, which underscores the heavy clinical and economic burden of this phenomenon in Georgia.

Synergistic quantification of mixed insulin preparations using time domain NMR techniques

Diabetes patients often rely on tailored insulin therapies, necessitating precise blends of various insulin types to achieve optimal pharmacokinetic profiles, including the quantity and action duration of insulin absorption into the bloodstream. This study aimed to develop an accurate quantification method for mixed insulin preparations, consisting of Insulin-NPH and Insulin Regular in ratios varying between 0:100–100:0. Time Domain NMR (TD-NMR) techniques, T2 relaxation times, and T1T2 maps were used to analyze the mixtures. Individually, neither technique provided a reliable determination of insulin ratios. However, the integration of both methods through chemometrics has been proven to be a synergistic approach, yielding a robust quantification technique suitable for quality control in the assessment of mixed insulin drugs. This innovative combined TD-NMR method is non-invasive, cost-effective, and user-friendly, offering at the same time a significant potential for preventing health complications associated with improper insulin dosing. Furthermore, our work elucidates the broader applicability of converging multiple TD-NMR techniques for analyzing intricate mixtures.

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

Impact of medication dosage on Helicobacter pylori eradication rates among pediatric patients.

Helicobacter pylori rates of eradication to common first-line regimens continue to decline globally. Prescription of the appropriate medication dosage is an important consideration, particularly in the pediatric population due to medication weight-based dosing. Limited data is available on the impact of guideline-recommended weight-based dosing on the successful eradication of H. pylori in children. Retrospective study of patients with histologic evidence of H. pylori from two pediatric tertiary care centers in New England. We excluded patients who were not treated or those missing eradication data. We compared the eradication rates of patients prescribed recommended weight-based dosages, duration, and frequency of treatment with those who were not. One hundred forty-four patients were included. The overall eradication rate was 73.6% (106/144). All treatment regimens were properly prescribed for 14 days. There was a high rate of improper weight-based dosing: proton pump inhibitor (PPI) 31.2% (45/144), amoxicillin 31.7% (39/123), metronidazole (MET) 19.4% (12/62), clarithromycin (CLA) 23.9% (22/70), tetracycline 50% (6/12), bismuth 26.1% (6/23). When PPIs were properly weight-dosed, there was a 78.8% eradication rate that dropped to 62.2% with suboptimal dosing (p = 0.036, OR: 2.26, CI: 1.04-4.87). When amoxicillin was properly weight-dosed, successful eradication was achieved in 81% versus only 53.8% when improperly dosed (p = 0.002; OR: 3.64, CI: 1.58-8.37). There was no statistically significant impact on eradication rates with improper weight-based dosing of MET, CLA, tetracycline, or bismuth. Proper weight-based dosing of amoxicillin and PPI is important for the successful eradication of H. pylori among children in the New England area.

Computer vision to enhance healthcare domain: An overview of features, implementation, and opportunities

The emergence of Artificial Intelligence (AI) has already brought several advantages to the healthcare sector. Computer Vision (CV) is one of the growing modern AI technologies. The distribution and administration of medications are about to change by using CV for medication management. This system scans pharmaceutical labels and keeps track of the process from delivery to administration using cameras, sensors, and computer algorithms. In order to assure accuracy in medicine delivery and dose, the system also makes it easier for doctors, nurses, and chemists to communicate. The computer vision-driven medication management system can significantly lower the number of medical mistakes that result from inaccurate or missing prescriptions, improper doses, or simply forgetting to take a particular drug. An exhaustive literature review has been done to identify work related to the research objectives. This paper is about CV and their need in healthcare. Various tasks associated with CV in the healthcare domain are discussed. Targeted healthcare goals through CV traits are briefed. Finally, the significant applications of CVs in healthcare were identified and discussed. Nowadays, CV has practical uses in healthcare. Its methods are widely used since they have shown excellent utility in several medical contexts, including medical imaging and surgical planning. The CV is used to study how to program computers to comprehend digital pictures. Numerous medical applications utilise this technology, such as automated abnormality identification, illness diagnosis, and surgical procedure guiding. CV is expanding quickly and has enormous promise to enhance healthcare. Some of the many CV applications in the healthcare sector include patient identification systems, medical picture analysis, surgical simulation and illness diagnosis.

Blok Pleksus Servikalis Superfisialis pada Insisi Abses Submandibula

This case study explores the use of bilateral superficial cervical plexus block as a regional anesthesia method in a 44-year-old male patient with a submandibular abscess. The patient, who has comorbidities of type 2 diabetes mellitus, renal insufficiency, and grade 1 obesity, underwent a 60-minute abscess drainage incision operation. This technique was chosen based on patient factors and the medical team's preference, avoiding the risks associated with general anesthesia. Lidocaine 2% at 6cc per side was used, demonstrating the effectiveness of the cervical plexus block in this procedure and others such as lymph node dissection and laceration repair. The study confirms that regional anesthesia guided by ultrasound is a quick, resource-efficient, and safe option, with the potential to avoid improper analgesic dosing. For longer procedures, local anesthetics like ropivacaine or bupivacaine can be utilized. The main conclusion is that the superficial cervical plexus block is an effective and safe alternative for anesthesia in certain neck procedures.

Study of Resistance of Aedes aegypti Mosquitoes to Pyrethroids by Free-flight Method

Efforts to combat dengue hemorrhagic fever (DHF) in Bali are focused on controlling the vector of Aedes aegypti Mosquitoes. One method is fumigation (fogging) with insecticides. The use of insecticides for a long time and improper doses can trigger resistance. Many countries including Indonesia have reported incidents of insecticide resistance. Methods for determining the level of insecticide resistance are bioassay, biochemistry, and gene mutation. The method does not describe the actual environmental conditions of Mosquitoes. Queensland Institute of Medical Research (QIMR) Berghofer developed a free-flight test procedure to evaluate insecticide resistance in free-flying mosquito conditions. The study, which was conducted in June 2019-January 2020, aimed to measure the level of insecticide resistance with the free-flight method in the A. aegypti population in North Denpasar. A total of 20 female A. aegypti aged 5-10 days were released in the free-flight room for 24 hours with permethrin or cypermethrin insecticide boards. The level of resistance is determined based on the mosquito mortality rate using WHO standards. The results showed permethrin and cypermethrin resistance in the A. aegypti population of North Denpasar, with mortality of less than 80%.

Frontline treatment options for higher-risk MDS: can we move past azacitidine?

Although remarkable international efforts have been ongoing for over 17 years to improve upon azacitidine, representing the standard of care therapy for higher-risk myelodysplastic neoplasms (MDS), there still has not been a positive randomized trial in comparison to azacitidine. Real-world data from numerous trials have shown similar results with a median overall survival of 14-18 months, a 40%-50% overall response rate, and a complete remission rate close to 20%. Despite these outcomes, 6 randomized controlled trials have failed to improve outcomes in this patient population, although relevant issues in some of these studies included improper dose adjustments of the hypomethylating agent, lack of placebo- controlled studies, and lack of overall survival (OS) as a primary endpoint, among others. Critical updates in MDS management include the development of molecular prognostication models (eg, the molecular international prognostic scoring system), updates in classification systems highlighting significant overlap in patients with MDS-increased blasts and acute myeloid leukemia (most relevant to TP53 mutations), and refinement of response criteria. Although these paradigm-shifting studies have had great impact in MDS management, the current ongoing randomized phase 3 trials were initiated prior, and prognostic stratification remains via the revised international prognostic scoring system) and with bone marrow blast counts of <20%. Notably, azacitidine + venetoclax, azacitidine + sabatolimab, and azacitidine + magrolimab have shown exciting results in large, single-arm studies and have completed accrual in placebo-controlled, double-blind studies with OS as a primary endpoint. We all eagerly await the results of these studies.

Exposure of Tritrichomonas foetus to sublethal doses of metronidazole induces a specific proinflammatory response in murine macrophages.

Tritrichomonas foetus is a flagellated parasite that primarily infects the reproductive tissues of livestock, causing bovine trichomoniasis. The cytoplasmic membrane of T. foetus contains various compounds that contribute to adherence, colonization, and pathogenicity. Metronidazole (MTZ) is the main treatment for trichomoniasis, but the emergence of drug-resistant strains is a concern due to improper use and dosing. T. foetus infection induces inflammation, and macrophages are key players in the immune response. However, our understanding of the host's immune response to T. foetus is limited, and the specific mechanisms underlying these responses are not well understood. This study aimed to investigate the impact of T. foetus surface proteins from trophozoites cultured under different sublethal MTZ conditions (MTZ-treated T. foetus MPs) on macrophage activation. By analyzing cytokine levels and gene expression in murine macrophages, we demonstrated that MTZ-treated T. foetus MPs induce a specific proinflammatory response. MTZ-treated T. foetus MPs-exposed macrophages exhibited a higher NO and H2 O2 production and overexpression of iNOS and NOX-2 genes in comparison to untreated T. foetus. Additionally, MTZ-treated T. foetus MPs triggered a significant induction of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ, as well as the overexpression of the TLR4, MyD88, and NF-κB genes on murine macrophages. The study aimed to unravel the immunological response and potential proinflammatory pathways involved in T. foetus infection and MTZ stress. Understanding the immune responses and mechanisms through which T. foetus surface proteins activate macrophages can contribute to the development of new therapeutic strategies for controlling bovine trichomoniasis.

Thioglycolic acid-capped gold nanoparticle/cytochrome P450-2E1 electrochemical biosensor for isoniazid

Tuberculosis (TB) is one of the deadliest diseases in Africa and it is classified as a serious global health problem. A new threat associated with the disease is the emergence of multidrug-resistant TB (MDR-TB), which results from improper dose or non-compliance with a treatment regime. It is, therefore, important to determine a patient’s rate of TB drug metabolism at a point-of-care, in order to enable appropriate dose prescription. This work presents a novel enzymatic nanobiosensor for real-time determination of isoniazid (INH), which is a highly prescribed drug for TB treatment. The nanobiosensor consists of a cytochrome P450-2E1 (CYP2E1) isoenzyme covalently attached to a screen printed or disk gold electrode (Au), functionalized with thioglycolic acid-capped gold nanoparticle (TGA-AuNP). The nanomaterial was green-synthesized with banana peel extract (BPE) as the reducing agent. It exhibited an ultraviolet-visible spectroscopy (UV–Vis) signature absorption band for AuNP at 536 nm and a direct bandgap energy (Eg) value of 2.00 eV. Fourier transform infra-red spectroscopy (FTIR) was used to confirm the reduction of Au3+ to Au0. High-resolution transmission electron microscopy (HR-TEM) and high-resolution scanning electron microscopy (HR-SEM) studies indicated that TGA-AuNPs were polydisperse and exhibited spherical morphology. Bovine serum albumin (BSA) and CYP2E1 were attached to the TGA-AuNPs-modified Au electrode using glutaraldehyde (Glu) as binder, to form the nanobiosensor (BSA/CYP2E1/Glu/TGA-AuNPs/Au). Differential pulse voltammetric (DPV) responses of the nanobiosensor for INH were determined in 10 mM phosphate buffer (pH 7.4). The limit of detection (LOD) and the limit of quantification (LOQ) values of the nanobiosensor were 0.0556 μM INH and 0.1683 μM INH, respectively.

Pharmacist interventions for appropriate COVID-19 antiviral therapy in long-term care facilities: A public health initiative

Background: Prescribing errors related to the COVID-19 oral antiviral agent nirmatrelvir-ritonavir have been reported and are primarily due to improper renal dosing and significant drug–drug interactions. These patient safety issues are particularly concerning in the long-term care facility (LTCF) population. The Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) is a unique collaborative partnership involving the University of Nebraska Medical Center, Nebraska Medicine, and the Nebraska Department of Health and Human Services (DHHS). ASAP is funded through the Nebraska DHHS healthcare-associated infections and antimicrobial resistance (HAI/AR) program and was established in 2016, with a primary focus of promoting safe and effective antimicrobial use in Nebraska. In 2022, ASAP developed a statewide pharmacist-led service to assist LTCFs in evaluating prescriptions for COVID-19 oral therapeutics. We studied the impact of ASAP pharmacist intervention on COVID-19 oral antiviral prescriptions. Methods: ASAP created a centralized LTCF treatment request process for oral antivirals. A REDCap survey hosted on a dedicated program webpage was used to collect requests for treatment submitted by any LTCF in Nebraska, including assisted living facilities. An ASAP pharmacist reviewed each survey submission for renal and hepatic function, drug–drug interactions, date of symptom onset, and ability to take oral medications. After pharmacist approval, delivery of the appropriate COVID-19 therapeutic to the LTCF was coordinated with the dispensing pharmacy. The pharmacists recorded the specific interventions for each treatment in the program database. Descriptive analyses were used to study the program impact. Results: In total, 630 courses of oral COVID-19 antivirals were administered to Nebraska LTCF residents through the ASAP program in 2022. The median patient age was 84 years, and 59% were female. Most dispensed courses (n = 410, 65%) needed pharmaceutical interventions upon review for 506 individual interventions. The most frequent intervention was to hold or adjust doses of concomitant medications in 205 patients (33%), followed by antiviral dose adjustment for renal function in 117 patients (19%), and selecting an alternative COVID-19 therapy due to drug–drug interactions in 108 patients (17%). COVID-19 therapeutic agents were changed upon ASAP intervention to be in compliance with the National Institute of Health COVID-19 treatment guidelines in 37 patients (6%). Conclusions: Pharmacist review of oral antiviral prescriptions for COVID-19 through a public health–supported initiative identified and prevented potential patient safety issues in LTCF residents. Future studies should analyze the impact of similar interventions on patient outcomes.Disclosures: None

SELISARC: A Spanish Sarcoma Group (GEIS) phase I/II trial of selinexor plus gemcitabine in selected sarcoma subtypes—Results of the phase I part.

11520 Background: Selinexor (KPT-330) (S), a small-molecule inhibitor of the nuclear export mediator exportin-1 (XPO-1), is able to reduce mRNA and protein expression of DNA damage repair (DDR) gene products, being synergistic with DNA damage agents as gemcitabine (G) in preclinical experiments. We hypothesized that selinexor would have a synergistic effect with gemcitabine in selected sarcoma patients (pts). Methods: Adult progressing pts, ECOG 0-1, with up to 2 previous systemic therapies for advanced disease (localized unresectable/metastatic) with centrally confirmed diagnosis of undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma (LMS), alveolar soft part sarcoma (ASPS), or osteosarcoma (OS) were eligible. S (days 1, 8, 15) and G (days 1, 8) were given in four dose levels, L1: S 60 mg + G 1,000 mg/m2 30 min, L2: S 60 mg + G 1,000 mg/m2 (10 mg/m2/min), L3: S 60 mg + G 1,200 mg/m2 (10 mg/m2/min), and L4: S 80 mg + G 1,200 mg/m2 (10 mg/m2/min). A -1 level was defined with S 60 mg + G 800 mg/m2 (30 min). A classic 3+3 design was used to determine the RP2D based on DLTs observed during the first 21-day cycle. In vitro research was performed in LMS and OS cell lines to test the synergy of the combination (MTS and flow cytometry assays). Results: Between November 2020 and June 2022, 17 pts (M/F 9/8), ECOG 0/1 (14/3), median age 50 years (22-71) were recruited. The median of previous lines was 1 (1-2). Diagnosis was: 9 LMS (52.9%), 6 OS (35.3%), 1 ASPS and 1 synovial sarcoma (SS) (5.9%). Three pts were treated in each of the first 3 levels and 8 pts in L4 (2 pts were not evaluable for DLT due to improper dosing). Only one DLT was observed in L4 (G4 thrombocytopenia) and this level was selected as RP2D. G3/4 toxicity: Neutropenia (52.9%), thrombocytopenia (41.2%), febrile neutropenia (11.8%), anemia, nausea, asthenia, vomiting, alopecia, and lipase increased (5.9% each). There were 3 RECIST PR, 7 SD, and 7 PD. Median PFS for LMS was 7 months (95% CI: 3-11). No relevant clinical activity was observed in OS. In vitro cell viability studies shown that S+G was synergistic in the majority of LMS cell lines tested (combination index of 0.789 for CP0024, 0.791 for SK-UT-1, 0.604 for AA and 1.186 for IEC005). However, our results indicated antagonism of S+G in OS cell lines, with values for the combination index of 1.67 for MG63, 1.54 for SAOS2 and 1.23 for U2OS. Apoptosis assays by flow cytometry confirmed these observations in LMS and OS cells. Conclusions: At the RP2D, S 80 mg + G 1,200 mg/m2 (10 mg/m2/min) is a feasible scheme with manageable toxicity. S+G has shown promising clinical activity for LMS, which warrants further investigation in a phase II. Preclinical studies shown the synergy and the antagonism of S+G in LMS and OS, respectively. Clinical trial information: NCT04595994 .

Safety and mortality outcomes for direct oral anticoagulants in renal transplant recipients.

Direct oral anticoagulants (DOACs) are increasingly used in renal transplant recipients (RTR), but relatively understudied in this population. We assess the safety of post-transplant anticoagulation with DOACs compared to warfarin. We conducted a retrospective study of RTRs at the Mayo Clinic sites (2011-present) that were anticoagulated for greater than 3 months excluding the 1st month post-transplant. The main safety outcomes were bleeding and all-cause mortality. Concomitant antiplatelet and interacting drugs were noted. DOAC dose adjustment was assessed according to common US prescribing practices, guidelines, and/or FDA labeling. The median follow-up was longer for RTRs on warfarin (1098 days [IQR 521, 1517]) than DOACs (449 days [IQR 338, 942]). Largely, there were no differences in baseline characteristics and comorbidities between RTRs on DOACs (n = 208; apixaban 91.3%, rivaroxaban 8.7%) versus warfarin (n = 320). There was no difference in post-transplant use of antiplatelets, immunosuppressants, most antifungals assessed, or amiodarone. There was no significant difference in incident major bleeding (8.4 vs. 5.3%, p = 0.89), GI bleeding (4.4% vs. 1.9%, p = 0.98), or intra-cranial hemorrhage (1.9% vs. 1.4%, p = 0.85) between warfarin and DOAC. There was no significant difference in mortality in the warfarin group compared to DOACs when adjusted for follow-up time (22.2% vs. 10.1%, p = 0.21). Rates of post-transplant venous thromboembolism, atrial fibrillation or stroke were similar between the two groups. 32% (n = 67) of patients on DOACs were dose reduced, where 51% of those reductions were warranted. 7% of patients that were not dose reduced should have been. DOACs did not have inferior bleeding or mortality outcomes compared to warfarin in RTRs. There was greater use of warfarin compared to DOACs and a high rate of improper DOAC dose reduction.

A Descriptive Analysis of Direct Oral Anticoagulant Drugs Dosing Errors Based on Spontaneous Reports from the EudraVigilance Database.

Direct oral anticoagulant drugs (DOACs) interfere with the coagulation process, thus improving patient care for those who require anticoagulant treatment. This study presents a descriptive analysis of adverse reactions (ADRs) attributed to DOAC dosage errors (overdose, underdose, and improper dose). The analysis was performed based on the Individual Case Safety Reports from the EudraVigilance (EV) database. Results show that data reported for rivaroxaban, apixaban, edoxaban, and dabigatran are mostly regarding underdosing (51.56%) compared to overdosing (18.54%). The most dosage error reports were identified for rivaroxaban (54.02%), followed by apixaban (33.61%). Dabigatran and edoxaban had similar percentages (6.26% and 6.11%, respectively) regarding dosage error reports. Since coagulation issues can become life-threatening events, and factors such as advanced age and renal failure can influence the pharmacokinetics of drugs, the correct usage of DOACs is of utmost importance for the management and prevention of venous thromboembolism. Thus, the collaboration and the complementarity of knowledge of physicians and pharmacists may offer a reliable solution for DOAC dose management and improve patient care.