Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.

PURPOSE: The prevalence of follow-on and compounded products of glucagon-like peptide-1 analogs is increasing. We assessed glucagon-like peptide-1 analogs semaglutide and liraglutide for purity, potential immunogenicity, and expected stability, by comparing a representative selection of commercially available follow-on drug substances (DSs) and drug products (DPs) with their corresponding originators. METHODS: Tests included several chromatography methods coupled with ultraviolet and mass spectrometry detectors, inductively coupled plasma optical emission spectroscopy, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, dissolution analyses, in silico peptide/major histocompatibility complex II-binding prediction, and fibrillation assays. RESULTS: Overall, 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide follow-on products were analyzed alongside originator products. Compared with originator, follow-on injectable semaglutide DSs and DPs had new impurities and impurity patterns, including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Analyses showed that several commercialized follow-on oral semaglutide DPs had a markedly lower quantity of semaglutide than the label claim, while dissolution tests indicated different semaglutide and sodium N-(8-[2-hydroxybenzoyl] amino)caprylate (SNAC) release profiles, which may reduce bioavailability. Neoepitopes were identified in DS and DP semaglutide follow-ons, indicating potential immunogenicity. Fibrillation assays showed increased fibrillation tendency and reduced physical stability in liraglutide follow-on DP samples compared with originator. CONCLUSION: This study highlights that differences in the manufacturing processes of follow-on semaglutide and liraglutide (vs those used for originators) can result in several changes to the DSs and DPs. The impact of these changes on efficacy and safety outcomes remains unknown and should be investigated by clinical studies.

Image quality improvement in single plane-wave imaging using deep learning.

In ultrasound image diagnosis, single plane-wave imaging (SPWI), which can acquire ultrasound images at more than 1000 fps, has been used to observe detailed tissue and evaluate blood flow. SPWI achieves high temporal resolution by sacrificing the spatial resolution and contrast of ultrasound images. To improve spatial resolution and contrast in SPWI, coherent plane-wave compounding (CPWC) is used to obtain high-quality ultrasound images, i.e., compound images, by coherent addition of radio frequency (RF) signals acquired by transmitting plane waves in different directions. Although CPWC produces high-quality ultrasound images, their temporal resolution is lower than that of SPWI. To address this problem, some methods have been proposed to reconstruct a ultrasound image comparable to a compound image from RF signals obtained by transmitting a small number of plane waves in different directions. These methods do not fully consider the properties of RF signals, resulting in lower image quality compared to a compound image. In this paper, we propose methods to reconstruct high-quality ultrasound images in SPWI by considering the characteristics of RF signal of a single plane wave to obtain ultrasound images with image quality comparable to CPWC. The proposed methods employ encoder-decoder models of 1D U-Net, 2D U-Net, and their combination to generate the high-quality ultrasound images by minimizing the loss that considers the point spread effect of plane waves and frequency spectrum of RF signals in training. We also create a public large-scale SPWI/CPWC dataset for developing and evaluating deep-learning methods. Through a set of experiments using the public dataset and our dataset, we demonstrate that the proposed methods can reconstruct higher-quality ultrasound images from RF signals in SPWI than conventional method.

Physical Compatibility Between Intravenous Magnesium Sulfate and Potassium or Sodium Phosphate in a Pediatric Intensive Care Unit.

Objective:To evaluate the physical compatibility between intravenous magnesium sulfate and potassium and sodium phosphate, a common electrolyte intravenous supplementation in pediatric intensive care units. Study design: Magnesium sulfate was mixed separately with potassium phosphate and sodium phosphate at ratios of 1:1, 1:4, and 4:1. Binary mixtures were prepared, in triplicate and under sterile conditions, by permuting the order of addition. The undiluted pure drugs were used as controls for possible sequence effects. Visual changes, turbidity, and pH were assessed immediately after mixing (baseline) and at 4 and 24 hours. Two observers performed visual changes by naked-eye visual inspection in order to search visible haze, particulate matter, gas formation, or color change. Turbidity was measured by nephelometry and incompatibility was defined as an increase of ≥0.5 nephelometric turbidity units (NTU) from baseline. pH was measured using a portable pH meter and incompatibility was defined as a variation of >1 pH unit during the observation period. Results: None of the admixtures exhibited visual changes or significant variations in turbidity (increases of ≥0.5 in nephelometric turbidity units) or pH (changes of >1 unit) during the observation period and neither compared with baseline. Conclusion: In this study, no visual changes were observed, and turbidity and pH evaluated by instrumental methods remained within acceptable limits and showed no significant variations from baseline, therefore no physical incompatibility between magnesium sulfate and potassium or sodium phosphate was found.

Effects of parenteral nutrition supplemented with beta-hydroxy-beta-methylbutyrate on gut-associated lymphoid tissue and morphology in mice.

BACKGROUND: Parenteral nutrition (PN) without enteral nutrition (EN) leads to marked atrophy of gut-associated lymphoid tissue (GALT), causing mucosal defense failure in both the gut and the extraintestinal mucosal system. We evaluated the effects of beta-hydroxy-beta-methylbutyrate (HMB) on GALT and gut morphology in PN-fed mice. METHODS: Experiment 1: male Institute of Cancer Research mice were assigned to the Chow (n = 12), Control (standard PN: n = 10), or H600 and H2000 (PN containing 600 mg/kg or H2000 mg/kg body weight of Ca-HMB: n = 12 and 10, respectively) groups. After 5 days of dietary manipulation, all mice were killed and the whole small intestine was harvested. GALT lymphocyte cell numbers and phenotypes of Peyer patch (PP), intraepithelial space, and lamina propria lymphocytes were evaluated. Experiment 2: 47 mice (Chow: n = 12; Control: n = 14; H600: n = 11; and H2000: n = 10) were fed for 5 days as in experiment 1. Proliferation and apoptosis of gut immune cells and mucosa, and protein expressions (mammalian target of rapamycin [mTOR], caspase-3, and Bcl2) were evaluated in the small intestine. RESULTS: Compared with the Controls, the Chow and HMB groups showed significantly higher PP cell numbers, prevented gut mucosal atrophy, inhibited apoptosis of gut cells, and increased their proliferation in association with increased mTOR activity and Bcl2 expression. CONCLUSION: HMB-supplemented PN is a potentially novel method of preserving GALT mass and gut morphology in the absence of EN.

Ultrasound-Assisted Extrusion Compounding of Nano Clay/Polypropylene Nano Compounds.

The incorporation of nanoparticles can significantly enhance the properties of polymers. However, the industrial production of nanocomposites presents a technological challenge in achieving the proper dispersion of nanoparticles within the polymer matrix. In this work, a novel device is presented that can be seamlessly integrated with standard twin-screw extruders, enabling the application of ultrasonic vibration to molten polymeric material. The primary objective of this study is to experimentally validate the effectiveness of this technology in improving the dispersion of nanoparticles. To accomplish this, a comparative analysis was carried out between nanocomposites obtained through conventional compounding extrusion and those processed with the assistance of ultrasonic vibrations. The nanocomposites under investigation consist of a polypropylene (PP) matrix reinforced with nano clays (Cloisite 20A) at a target loading ratio of 5% by weight. To comprehensively evaluate the impact of the ultrasound-assisted compounding, various key properties were assessed, such as the melt flow index (MFI) to characterize the flow behavior, mechanical properties to evaluate the structural performance, oxygen barrier properties to assess potential gas permeability, and microstructure analysis using Scanning Electron Microscopy (SEM) for detailed morphology characterization. The results suggested an improvement in nanoparticle dispersion when using the ultrasound device, particularly when the intensity was adjusted to 60%.

An inverse lomax-uniform poisson distribution and joint modeling of repeatedly measured and time-to-event data in the health sectors.

Methodological developments in different sectors like health, biomedical and biological areas are the recent burning issue in the statistical literature. The approach of implementing declining hazard function which is obtained by compounding truncated Poisson distribution and a lifetime distribution is a special concern in a few studies. In this paper we proposed a newly introduced distribution called inverse Lomax-Uniform Poisson distribution mostly applied in the health, biomedical, biological, and related sectors. Some basic statistical properties of the distribution are discussed. The capability of the model is checked by comparing it with six potential models by using a practical real data set. Based on the comparison techniques, the newly proposed model out performs all its counterparts. The simulation study is also conducted. Furthermore, the joint modelling of repeatedly measured and time-to-vent processes is discussed in detail with the real data set in the health sector.

Enhanced 2D Hand Pose Estimation for Gloved Medical Applications: A Preliminary Model.

(1) Background: As digital health technology evolves, the role of accurate medical-gloved hand tracking is becoming more important for the assessment and training of practitioners to reduce procedural errors in clinical settings. (2) Method: This study utilized computer vision for hand pose estimation to model skeletal hand movements during in situ aseptic drug compounding procedures. High-definition video cameras recorded hand movements while practitioners wore medical gloves of different colors. Hand poses were manually annotated, and machine learning models were developed and trained using the DeepLabCut interface via an 80/20 training/testing split. (3) Results: The developed model achieved an average root mean square error (RMSE) of 5.89 pixels across the training data set and 10.06 pixels across the test set. When excluding keypoints with a confidence value below 60%, the test set RMSE improved to 7.48 pixels, reflecting high accuracy in hand pose tracking. (4) Conclusions: The developed hand pose estimation model effectively tracks hand movements across both controlled and in situ drug compounding contexts, offering a first-of-its-kind medical glove hand tracking method. This model holds potential for enhancing clinical training and ensuring procedural safety, particularly in tasks requiring high precision such as drug compounding.

Safeguarding Patients with End-Stage Kidney Disease From Climate-driven Extreme Heat and Hurricanes.

5wPatients with end stage kidney disease (ESKD) who receive in-center hemodialysis are disproportionately vulnerable to extreme weather events, including hurricanes and heat waves, that may disrupt access to healthcare providers, and life-sustaining treatments. This current era of climate-driven compounding disasters is progressively elevating the level of threat to the health and well-being of patients with ESKD. This analysis brings together multi-disciplinary expertise to explore the contours of this increasingly complex risk landscape. Despite the challenges, important advances have been made for safeguarding this medically high-risk patient population. Hemodialysis services providers have devised innovative systems for preparing their patients and sustaining, or rapidly reestablishing, hemodialysis services in the aftermath of a disaster, and maintaining open lines of communication with their caseloads of ESKD patients throughout all phases of the event. A description of lessons learned along the path towards improved patient support in disasters, is provided. The article concludes with a detailed case example, describing dialysis providers' effective response throughout Hurricane Ian's passage across the State of Florida in 2022. Based on lessons learned, this analysis outlines strategies for protecting patients with ESKD that may be adapted for future climate-potentiated disaster scenarios.

Considerations for developing a health-system 503B outsourcing strategy.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To provide guidance for health systems on how to develop a strategy for utilizing 503B outsourcing facilities for sterile product preparation. SUMMARY: Health-system pharmacies face an increasingly complex set of challenges related to providing sterile products to patients. New United States Pharmacopeia <797> regulations, increasing drug shortages, and an ongoing pharmacy technician workforce shortage have made sterile compounding more difficult than ever for health-system pharmacies. Outsourcing of production to 503B outsourcing facilities is one strategy pharmacy leaders can use to help navigate these challenges. However, there are many factors to consider when deciding whether to outsource a product and which 503B vendors are safe and reliable. The Cleveland Clinic Health System (CCHS) has developed a robust internal structure to appropriately vet 503B outsourcing facilities for safety and reliability, as well as standardized criteria used to determine which products will be outsourced. This article describes the tools CCHS has used to evaluate 503B outsourcing vendors and to evaluate individual products to determine the pros and cons of outsourcing vs insourcing. Additionally, general considerations regarding outsourcing are described. CONCLUSION: Outsourcing to 503B facilities can be an effective strategy for navigating sterile compounding challenges but is not without some risk. Pharmacy leaders must develop a standardized approach to thoroughly evaluate 503B vendors and products to ensure their outsourcing strategy is both safe and cost-effective.

Stability of intravenous medicines - evidence of maximum temperature reached in both summer and winter within soft shell elastomeric pumps.

OBJECTIVE: Elastomeric devices or pumps are a valuable tool to deliver outpatient parenteral therapy and have been used for administration of chemotherapy, antibiotics and pain medication. A key determinant of effective treatment is to consider the stability of medicines within these devices. It is widely known that an increase in temperature positively correlates to an increase in drug degradation. The objective of our work was to measure the temperature within soft shell elastomeric devices, under simulated outpatient treatment conditions in summer and winter months, and to determine the maximum temperature reached within these periods of use. METHODS: Thermocouples were inserted within soft shell Easypump II (B Braun Medical, Sheffield, UK) elastomeric pumps and the temperature was monitored under simulated outpatient conditions during cold and warm weather with different fill volumes. Temperature monitoring was also conducted with varying levels of insulation around the devices. RESULTS: Our results show that internal temperatures remained below 32°C±1°C in winter and summer months, including during times defined as a heatwave. Fill volume and ambient temperature were shown to be significant factors affecting the internal temperatures reached. CONCLUSION: A soft shell Easypump II elastomeric pump, if used within its carry pouch, will maintain the internal solution below a temperature of 32°C±1°C if patients correctly adhere to handling guidance. Our results show that further improvements to the insulation material used in carry pouches can significantly restrict the rate of temperature rise within the pumps and will give more assurance in relation to preventing degradation especially considering the increases in extreme weather conditions observed in recent years due to global warming.

Augmented Reality Eyewear for Assisting in the Preparation and Control of Cancer Therapies: Assessing the Learning Curve and Level of Adoption.

Since March 2022, the centralized cytotoxic preparation unit at the Lille University Hospital (Lille, France) is equipped with augmented reality eyewear for preparation and quality control. The technology enables a user-friendly guided step by step preparation process. It also assists the user by identifying vials through data matrix scan and recording photos at different stages of preparation in order to replace the in-process double visual inspection which will now be carried out a posteriori during the release control. In this paper, we evaluate user feedback and model the learning curve for this new tool. The team's feedback was evaluated using the System Usability Scale (SUS) and Short User Experience Questionnaire (S-UEQ). Both questionnaires showed very good acceptance of the tool by our teams, with scores of 79.7 for the SUS and 2.014 for the UEQ. Finally, a learning curve was drawn up according to Wright, showing a learning curve of 91%. This study shows that the tool has been very well integrated into our preparation unit.

Evaluation of the Amount of Compounded Chemotherapy Drugs: A Comparison Between Nine Compounding Pharmacies.

The use of compounded formulations of chemotherapy in veterinary medicine is common. The purpose of this study was to evaluate the drug amount of two compounded chemotherapeutics (chlorambucil and cyclophosphamide) from multiple veterinary compounding pharmacies, to determine if there was a difference in drug amounts between those that came from 503A versus 503B pharmacies, and finally to determine heterogeneity in drug amounts within each individual pharmacy. Nine veterinary compounding pharmacies (eight 503A, one 503B) were sampled in total, with two different batches sampled from each pharmacy. Each capsule's actual concentration was compared to the intended (prescribed) concentration. Of the 68 total samples obtained, 20 (29%) tested outside the FDA-acceptable discrepancy of ±10%. Of these, 12 (60%) were chlorambucil and 8 (40%) were cyclophosphamide. 503A cyclophosphamide samples had an average discrepancy of 6.6% from the intended dose while samples from the 503B pharmacy had a discrepancy of 1.8%. 503A chlorambucil samples had an average discrepancy of 10.4% from the intended dose while samples from the 503B pharmacy had a discrepancy of 9.6%. Heterogeneity within the same pharmacy and batch ranged from 0.1% to 51% for the 503A pharmacies and 2.6% to 7.5% for the 503B pharmacy. Heterogeneity between different batches within the same pharmacy ranged from 0.4% to 58.3% for the 503A pharmacies and 5% to 14.8% for the 503B pharmacy. Although the drug amounts of compounded cyclophosphamide and chlorambucil manufactured by the 503B compounding pharmacy was more reliably maintained compared to that compounded by the 503A pharmacies, there was ultimately still potential for variability in drug amounts regardless of the pharmacy designation.

Assessment of chemical contamination by cancer drugs during use of the RIVATM compounding robot: A pilot study.

INTRODUCTION: Many hospitals are now investing in robotic compounding system for the preparation of cytotoxic agents. The objective of the present study was to describe contamination by cytotoxics inside and outside the RIVATM robot (ARxIUM, Winnipeg, Canada). MATERIAL & METHODS: We applied a risk analysis to determine which locations inside and outside the compounding robot should be monitored. Samples were collected by swabbing with a wet swab (using 0.1 mL of sterile water) before the robots was cleaned. Ten cytotoxics compounded with the robot were screened for using LC-MS/MS. We determined the percentage contamination rates inside (CRin) and outside (CRout) the robot and the amounts of each contaminant (in ng/cm²). If a sample was found to be positive, a corrective action was implemented. RESULTS: Our risk analysis highlighted 10 locations inside the robot and 7 outside. Ten sampling campaigns (10 samples per campaign) were performed. The mean CRin (40%) was significantly higher than the mean CRout (2%; p < 10-4). Gemcitabine and cyclophosphamide were the main contaminants. After the implementation of corrective measures (such as daily cleaning with SDS/isopropyl alcohol), the CRin fell from 60% to 10%. DISCUSSION/CONCLUSION: The frequency of contamination was lower for robotic compounding than for manual compounding in an isolator. However, robotic compounding tended to generated larger mean amounts of contaminant; this was related to incidents such as splashing when syringes were disposed of after the compounding. The implementation of corrective actions effectively reduced the CRs. Further longer-term studies are required to confirm these results.

Cellular therapy site-preparedness: Inpatient pharmacy implementation at a large academic medical center.

BACKGROUND: With the recent Food & Drug Administration (FDA) approval of cellular therapy that requires product manipulation prior to administration in combination with a short stability window, the need was identified for local dose preparation within the pharmacy rather than the off-site stem cell processing laboratory. This approval gave rise to assessment of regulatory standards surrounding cellular therapy, evaluation and revision of current standard operating procedures and policies with formal process validation, assessment of occupational exposure mitigation and safety considerations, and development of staff training and education. OBJECTIVE: To describe and provide insight into the stepwise process of FACT validation and onboarding of commercially available cellular therapy products that require sterile compounding manipulation within a pharmacy prior to administration. DISCUSSION: A multidisciplinary effort is required to attain FACT certification and implement pharmacist compounding of cellular therapy products.1 Local preparation within a pharmacy facilitates a sound operational workflow and provides a pathway to perform aseptic manipulations of cellular therapy products safely and efficiently. CONCLUSION: Safe and successful administration of cellular therapies handled and compounded by pharmacy department staff along with program validation requires a preemptive review utilizing a multidisciplinary approach for process development. This manuscript will provide a foundation based on consistency and transparency in effective cellular therapy sterile compounding and aseptic manipulation, proper handling and disposal procedures, increased communication through creation and optimization of treatment plans and order-sets, standardized medical center staff education, and development of policies and standard operating procedures for the entire health care team.

Properties of EPDM Nanocomposites Reinforced with Modified Montmorillonite.

Considering the dilemma of obtaining economic and high-performance composites based on non-polar and main-chain-saturated ethylene propylene diene monomer rubber (EPDM), we proposed an effective and universal filler modification and nanocomposite preparation method. Specifically, the montmorillonite (MMT) surface was coated with polydopamine (PDA) to obtain DMMT, which was confirmed by XRD, XPS, FTIR, and TGA. After compounding DMMT gel with the solid EPDM via the gel compounding method, a silane coupling agent, vinyltrimethoxysilane, was introduced to construct covalent interactions between rubber and filler. Compared with the unmodified MMT filler EPDM, the EPDM/DMMT nanocomposite showed much fewer filler aggregates in the matrix. The highest tensile strength of the composites reached 6.5 MPa with 10 phr DMMT, almost 200% higher than that of pure EPDM.

Characterization of Liquid Dosage Forms of Atenolol and Enalapril Maleate for Oral and Enteral Feeding Administration.

The limited availability of pharmaceutical formulations tailored for cardiovascular diseases in both pediatric and geriatric populations generates the need for compounded dosage forms to guarantee precise dosing and medication adherence. This study aimed to analyze the physicochemical properties and stability of formulations of atenolol and enalapril maleate prepared with a proprietary oral vehicle, SuspendIt®. To this end, palatability, injectability, pH, rheological behavior, and physical, microbiological, and chemical stability over a 180-day storage period at 25 °C and 5 °C were evaluated. Injectability tests confirmed the suitable use of both formulations for administration through enteral feeding tubes. By using a potentiometric electronic tongue, it was confirmed that the SuspendIt® vehicle effectively served as a bitter-blocking strategy for atenolol and enalapril maleate. Adequate stability throughout the storage period was confirmed in terms of the mechanical properties, pH, and effectiveness of the preservative system. The atenolol concentration remained above 90% of the initial amount, while the concentration of enalapril maleate decreased to 88% after 90 days of storage at 25 °C. In summary, the atenolol formulation maintained suitable chemical, physical, and microbiological stability after 180 days at both storage temperatures, while the enalapril maleate formulation remained stable up to 60 days at 25 °C and for 180 days at 5 °C.

Long-Term Stability of Glycopyrrolate Oral Solution Galenic Compound at Different Storage Conditions.

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies.

Three-Dimensional Printing of PVA Capsular Devices for Applications in Compounding Pharmacy: Effect of Design Parameters on Pharmaceutical Performance.

The creation of products with personalized or innovative features in the pharmaceutical sector by using innovative technologies such as three-dimensional (3D) printing is particularly noteworthy, especially in the realm of compounding pharmacies. In this work, 3D printed capsule devices (CDs) with different wall thicknesses (0.2, 0.3, 0.4, 0.6, and 0.9 mm) and sizes were designed and successfully fabricated varying printing parameters such as extrusion temperature, printing speed, material flow percent, and nozzle diameter. The physicochemical, pharmaceutical, and biopharmaceutical performance of these CDs was evaluated with the aim of achieving an immediate drug release profile comparable to hard gelatin capsules (HGC) for use in magistral compounding. It was observed that the disintegration time of the CDs increased with wall thickness, which correlated with a slower drug release rate. CDs with configurations presenting 0.4 mm wall thickness and sizes comparable to HGC n° 0, 1, and 2 demonstrated satisfactory weight uniformity, short disintegration times, and immediate drug release, indicating their potential as effective devices in future compounding pharmacy applications. In addition, a modified Weibull-type model was proposed that incorporates wall thickness as a new variable in predicting dissolution profiles. This model improves the process of selecting a specific wall thickness to achieve the desired dissolution rate within a specified time frame.

Fourier-based beamforming for 3D plane wave imaging and application in vector flow imaging using selective compounding.

Objective. Ultrafast ultrasound imaging using planar or diverging waves for transmission is a promising approach for efficient 3D imaging with matrix arrays. This technique has advantages for B-mode imaging and advanced techniques, such as 3D vector flow imaging (VFI). The computation load of the cross-beam technique is associated with the number of transmit anglesmand receive anglesn. The full velocity vector is obtained using the least square fashion. However, the beamforming is repeatedm × ntimes using a conventional time-domain delay-and-sum (DAS) beamformer. In the 3D case, the collection and processing of data from different beams increase the amount of data that must be processed, requiring more storage capacity and processing power. Furthermore, the large computation complexity of DAS is another major concern. These challenges translate into longer computational times, increased complexity in data processing, and difficulty in real-time applications.Approach. In response to this issue, this study proposes a novel Fourier domain beamformer for 3D plane wave imaging, which significantly increases the computational speed. Additionally, a selective compounding strategy is proposed for VFI, which reduces the beamforming process fromm × ntom(wheremandnrepresent the number of transmission and reception, respectively), effectively shortening the processing time. The underlying principle is to decompose the receive wavefront into a series of plane waves with different slant angles. Each slant angle can produce a sub-volume for coherent or selective compounding. This method does not rely on the assumption that the plane wave is perfect and the results show that our proposed beamformer is better than DAS in terms of resolution and image contrast. In the case of velocity estimation, for the Fourier-based method, only Tx angles are assigned in the beamformer and the selective compounding method produces the final image with a specialized Rx angle.Main results. Simulation studies andin vitroexperiments confirm the efficacy of this new method. The proposed beamformer shows improved resolution and contrast performance compared to the DAS beamformer for B-mode imaging, with a suppressed sidelobe level. Furthermore, the proposed technique outperforms the conventional DAS method, as evidenced by lower mean bias and standard deviation in velocity estimation for VFI. Notably, the computation time has been shortened by 40 times, thus promoting the real-time application of this technique. The efficacy of this new method is verified through simulation studies andin vitroexperiments and evaluated by mean bias and standard deviation. Thein vitroresults reveal a better velocity estimation: the mean bias is 2.3%, 3.4%, and 5.0% forvx,vy, andvz, respectively. The mean standard deviation is 1.8%, 1.7%, and 3.4%. With DAS, the evaluated mean bias is 9.8%, 4.6%, and 6.7% and the measured mean standard deviation is 7.5%, 2.5%, and 3.9%.Significance. In this work, we propose a novel Fourier-based method for both B-mode imaging and functional VFI. The new beamformer is shown to produce better image quality and improved velocity estimation. Moreover, the new VFI computation time is reduced by 40 times compared to conventional methods. This new method may pave a new way for real-time 3D VFI applications.

Study of Leachable Compounds in Hospital Pharmacy-Compounded Prefilled Syringes, Infusion Bags and Vials.

Hospital pharmacy compoundings are crucial for maintaining patient care. They are time- and cost-effective in hospital pharmacy settings because they prevent waste, preparation errors, dosage errors, microbial contamination and breakage due to handling. Unfortunately, the drawbacks of hospital pharmacy compounding include the selection of inappropriate medical devices (MDs) for long-term storage, which could directly impact patients. In this study, three important hospital pharmaceutical compoundings, vancomycin in prefilled syringes (PFSs) made of polypropylene (PP) material, paediatric parenteral nutrition (PN) in ethylene vinyl acetate (EVA) bags and diluted insulin in cyclic olefin copolymer (COC) vials, were selected for leachate study and risk assessment. These compounds were studied via a semiquantitative screening approach by means of an ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) with postcolumn infusion and an in-house built database. 17 leachable compounds for the PFS, 25 for the PN, and 10 for the vial were identified, and their concentrations were estimated for toxicological assessments. In conclusion, all MDs used in hospital pharmacy compoundings were observed suitable thanks to risk assessments. However, suitable MDs recommended for long-term storage would remain with polymers like COC, for higher safety when exposed to frail and vulnerable patients like neonates and infants.