Journal of Pharmacy Technology最新文献

Objective: The objective of the study is to review the characteristics, efficacy, safety, and clinical relevance of sotatercept in pulmonary arterial hypertension (PAH). Data Sources: A literature search containing search terms related to sotatercept and PAH was conducted. Embase via Elsevier, MEDLINE via Ovid, the medRxiv preprint server, Cochrane Library CENTRAL trials registry, and ClinicalTrials.gov were searched from inception through October 31, 2024. The package insert was utilized to obtain drug information and additional data. Study Selection and Data Extraction: Phase II-III clinical trials investigating sotatercept for PAH were included. Articles written in English were extracted while animal studies and phase I clinical trials were excluded. Data Synthesis: In patients with WHO Group 1, functional class II-III PAH, adding sotatercept to background therapy increased 6-minute walk distance in phase II-III trials. Pooled analysis from PULSAR (phase II) and STELLAR (phase III) showed improvements in pulmonary vascular resistance and NT-proBNP. Exploratory data from PULSAR revealed that BMPR2 genetic variant status was not associated with significant differences in treatment effects. SPECTRA (phase IIb) demonstrated improved right ventricular structure and function. Interim analysis from SOTERIA showed that treatment effects persist at 1 year. Conclusions: Sotatercept is a viable add-on therapy for patients with PAH Group 1 and functional class II-III. Additional data are needed to assess long-term outcomes among treatment-naïve patients and those with the most severe symptomatology.

Background: Clinicians often use parenteral lead-in regimens prior to direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in hospitalized patients due to shorter half-life and the ability to use laboratory monitoring. Objective: This study evaluates the effectiveness and safety of different apixaban lead-in durations for hospitalized adults with newly diagnosed VTE. Methods: Retrospective review of patients with one of the following lead-in regimens: (1) parenteral anticoagulation ≥ 48 hours with abbreviated course of apixaban lead-in, (2) parenteral anticoagulation ≥ 48 hours with full apixaban lead-in, or (3) no parenteral anticoagulation with full apixaban lead-in. All followed by maintenance apixaban for at least 6 months. Primary outcomes were incidences of recurrent VTE (rVTE) or bleeding events, in accordance with International Society on Thrombosis and Hemostasis (ISTH) definitions, within 6 months of the index visit. Data are presented descriptively and univariate analyses between groups performed. Results: Sixty-eight patients were included; rVTE (all deep vein thrombosis (DVT)) occurred in 2 patients (2.9%) and bleeding events (all clinically relevant non-major bleeding) occurred in 3 patients (4.4%) overall. There were no differences between groups; one patient in the parenteral group had full lead-in and one patient in the full-lead apixaban group had rVTE. One patient in the parenteral with full lead-in and 2 patients in the full lead-in apixaban group had a bleeding event (P = 0.99). Mean time to rVTE or bleeding event was 46 and 158 days, respectively. Conclusions: Similar safety and effectiveness were noted between the 3 apixaban lead-in regimens. These findings suggest that all 3 regimens provide similar outcomes, warranting further investigation to optimize lead-in strategies.

Objective: To compare the efficacy and safety of 12-24 hours versus 72 hours of intravenous terlipressin therapy in patients with acute esophageal variceal bleeding (AVB). Data sources: A systematic search was conducted using PubMed, Scopus, Cochrane Library, Google Scholar, Web of Science, VHL, and ClinicalTrials.gov for studies published up to February 24, 2024. The search terms included "terlipressin," "variceal bleeding," "short-course," and "72-hour treatment." Study selection and data extraction: Randomized controlled trials (RCTs) comparing 12 to 24 hours with 72 hours of terlipressin therapy in patients with AVB were included. Studies not meeting these criteria or focusing on unrelated outcomes were excluded. Two authors conducted data extraction and bias assessment independently, with discrepancies resolved by a third reviewer. Baseline characteristics and outcomes (rebleeding and mortality within 5 days) were recorded. Results: Four RCTs with 469 patients were included in the analysis. There were no significant differences observed in 5-day rebleeding rates (OR = 0.943; 95% CI [0.384, 2.317]; P = 0.898) or mortality rates (OR = 0.386; 95% CI [0.066, 2.260]; P = 0.291) between terlipressin treatment durations of 12 to 24 hours and 72 hours within the first 5 days posttreatment. In addition, no heterogeneity was found in both variables (P > 0.1). Conclusion: This meta-analysis indicates that there is no significant difference in rebleeding rates or mortality between 12 to 24 hours and 72 hours of terlipressin therapy for AVB within 5 days posttreatment. Shorter treatment durations may offer advantages in terms of resource utilization and adverse event risk but require further validation through studies involving larger patient populations.

Background: Pharmaceutical waste represents a major burden to the health care system and environment. Proper drug waste disposal devices are vitally needed, especially for propofol solutions that inherently carry a high risk of microbial contamination. Objectives: The aims of this study were to compare the capabilities of 2 drug disposal systems for decontamination of propofol solutions inoculated with medical pathogens and assess chemical degradation of propofol after treatment with Fenton reagents. Methods: Standard microbiological assays were used to assess survival and growth of Escherichia coli and Candida albicans inoculated into propofol solutions. Both a prototype instrument and a commercially marketed disposal device were tested for their ability to kill microbial growth. Furthermore, a propofol bioanalytical assay utilizing high-performance liquid chromatography (HPLC) was developed to measure propofol concentrations before and after treatment with a Fenton reagent cocktail (iron and hydrogen peroxide). Results: Propofol emulsion and diluted solutions lack antimicrobial properties and support the growth of microbes. The prototype instrument effectively killed E. coli and C. albicans inoculated into propofol solutions, while the commercial product did not kill or inhibit the growth of the microorganisms. Finally, propofol was chemically degraded to undetectable quantities (< 0.13 ppm) upon exposure to Fenton reagents in a prototype instrument. Conclusions: We show for the first time that propofol solutions inoculated with microbes are decontaminated upon exposure to Fenton reagents. Treatment with Fenton reagents also chemically destroys the propofol molecule. These results will support the development of novel drug disposal devices for real-time application in the pharmacy setting.

Objective: To cultivate caregiver perspectives and empathy through computer-based simulations in the ambulatory care setting. Methods: A total of 46 third-year students were enrolled in the 2-week ambulatory care elective at the University of Florida College of Pharmacy. Students were assigned 5 computer-based simulated scenarios, each created to encompass elements regarding social determinants of health from a caregiver perspective. After each scenario, students were required to complete a post scenario assessment where students were tasked with reporting their emotional response by providing 3 adjectives upon completion. After completing all caregiver scenarios, students completed a postsimulation reflection connecting their experience with caring for their future ambulatory care patients. Both individual and final reflections were analyzed and assigned to the themes of emotional strife, compassion/understanding, self-reflection, resilience, and/or other to determine proportion of identified themes. Results: For the individual caregiver scenarios, the most identified theme was emotional strife amongst all scenarios (45%-68%). Regarding the final reflection, most of the theme identified were compassion/understanding (46%) followed by self-reflection (29%). Emotional strife was the least identified theme in the final reflection (7%). Conclusion: After students completed all the caregiver scenarios, students reported higher levels of compassion/understanding and self-reflection when compared with other identified themes. Through this computer-based simulation, students gained a better understanding and empathy toward the caregiver perspective when faced with common health care disparities in an ambulatory care patient population.

Background: Heparin infusions are used to treat and prevent thromboembolic complications in neurocritical care, but optimal dosing in patients with acute intracranial pathology or recent neurosurgery is uncertain, due to elevated risk of hemorrhage. Many institutions customize heparin nomograms for such patients but fail to methodically evaluate their effectiveness. Context: Neurocritical care unit in an academic medical center in the United States. Problem: Several incidents of heparin infusions failing to reach their partial thromboplastin time (PTT) goal within 24 hours of initiation occurred. This created a concern that existing heparin dosing protocol should be adjusted to attain goal PTT more rapidly to better treat thrombotic events. Objective: To reduce time to therapeutic effectiveness of weight-based heparin in neurocritical care patients at high risk of bleeding. Study Design: Quality improvement initiative, comparing data from a retrospective chart review (historical comparison cohort) and a prospective observational quality improvement initiative (QI cohort). Patients: Adult patients with acute intracranial pathology and acute indications for therapeutic anticoagulation but considered at high risk of intracranial hemorrhage. Interventions: Increase heparin dosing nomogram from 12 units/kg/h (historical cohort) to 18 units/kg/h (quality improvement cohort), without an initial bolus in either. Measurements: Primary endpoint was time to therapeutic activated partial thromboplastin time (aPTT) in hours, assessed with a Kaplan-Meier curve. Any known bleeding or thrombotic complications were recorded. Results: Time to reach therapeutic target aPTT was shorter in quality improvement cohort than in historical cohort (see Figure 1 in full text for details). Bleeding complications occurred in 3 of 21 patients in each cohort. Conclusions: Quality improvement initiatives such as this can make documented improvements in health care provided to neurocritical care patients.

Background: Calls to poison centers involving exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RA) have increased. Data from a statewide poison control system from 2017 to 2023 was analyzed to assess changes in GLP-1 RA exposure frequencies and reported clinical effects. Methods: Retrospective records review of all human exposure cases to GLP-1 RA reported to a statewide poison center from December 1, 2017 to December 31, 2023. Collected data were entered into REDCap (Research Electronic Data Capture). Changes in exposure frequency over time assessed with interrupted time series analysis (ITSA); the intervention was FDA approval of semaglutide (Wegovy) for chronic weight management in June 2021. Statistical analyses completed using Stata v17 or OpenEpi (v3.01). Results: One thousand forty-seven cases were included. Interrupted time series analysis identified an increase in reported GLP-1 RA exposures of 1.16 per month ([CI = 0.570, 1.802]; P < 0.001) and an increase in hospital utilization from exposures of 0.351 per month ([CI = 0.159, 0.544]; P = 0.001) following Wegovy approval. Common adverse effects were nausea (n = 295, 28.0%), vomiting (n = 267, 25.5%), dizziness (n = 63, 6.0%), abdominal pain (n = 54, 5.1%), and other gastrointestinal symptoms (n = 60, 5.7%). Most cases were managed at home (n = 696, 66.5%). Two hundred twenty (21.0%) patients were treated in the emergency department, and 46 (4.4%) were admitted. The most common reason for exposure was unintentional therapeutic error (n = 838, 80.0%). Five major (0.5%) and 72 moderate (6.9%) medical outcomes were reported. Hypoglycemia occurred in 40 (3.8%) patients. Thirty-six exposures involving compounded GLP-1 RA were identified; administration errors were the main reason for exposures among this subgroup (n = 33, 91.7%). Conclusion: Glucagon-like peptide-1 receptor agonist exposures and hospital utilization after exposure increased following Wegovy approval for weight management. Hypoglycemia, while infrequent, was reported; nondiabetic patients using GLP-1 RA should be educated on recognizing hypoglycemia. Additional patient education on GLP-1 RA administration and further study on the impact of compounded GLP-1 RA products are warranted.

Background: HIV treatment has advanced significantly with the introduction of simpler antiretroviral regimens, but adherence remains a challenge. In this context, the long-acting injectable combination cabotegravir/rilpivirine (CAB/RPV) emerges as a promising alternative to improve adherence and quality of life for patients. Objective: The purpose of this study was to determine the proportion of patients with HIV-1 on antiretroviral therapy (ART) who meet the criteria for the use of intramuscular CAB/RPV. Methods: A single-center, retrospective observational study was conducted on patients with HIV-1 receiving ART at a Spanish hospital. Adult patients with at least 6 months of stable ART and a viral load result in the previous 12 months were included. Pregnant women, patients with less than 6 months of ART, or those without a recent viral load were excluded. The primary endpoint was the proportion of patients meeting the criteria for intramuscular CAB/RPV: undetectable viral load, stable ART, adherence >90%, no resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs)/integrase strand transfer inhibitors (INSTIs), no enzyme inducers, no anticoagulants, and no hepatitis B virus (HBV) infection. We also measure the risk of virological failure. Costs and treatment complexity were analyzed. Results: A total of 194 patients were included. In total, 68% met the criteria for intramuscular CAB/RPV. The main reasons for ineligibility were a recent ART switch (16%) and lack of adherence (11.3%). The mean annual incremental cost per patient when switching to CAB/RPV was €651.51. Conclusion and Relevance: A considerable proportion of patients with HIV meet the criteria for intramuscular CAB/RPV. However, lack of adherence and the costs associated with intramuscular therapy represent barriers to its implementation. Strategies to improve adherence and cost-effectiveness studies are needed.