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.

Paediatric oral formulations: Why don't our kids have the medicines they need?

Medication use in children represents 15-20% of total drug sales. More than 50% of children receive at least one prescription medication a year. Despite this, few drugs have a paediatric formulation available. Furthermore, 80% of paediatric prescriptions are considered off-label. Off-label use is defined as the use of products that differ in dose, indication or route of administration from the one established in the summary of product characteristics. Off-label use is associated with an increased risk of adverse drug reactions, including therapeutic failure. The US Food and Drug Administration and the European Medicines Agency have made changes to regulations to incentivize the development of paediatric formulations. Novel paediatric formulations can ease drug administration, reducing medication errors, increasing dosing acceptability, medication adherence and improve safety. Two routes for paediatric drug approval are available, the traditional, requiring clinical trials and the formulation bridging path, where these formulations need to demonstrate equivalence with the existing adult formulations. New formulations seeking regulatory approval require bioequivalence studies, but the regulatory framework, which states that bioequivalence data are obtained from adults and then extrapolated to children, may be disregarding important physiological differences between these two populations of patients. It is important to ensure that drugs for children have been appropriately studied and are properly manufactured for them. Adequately designed studies will provide data that will improve our understanding of how drug disposition differs between adults and children and will pave the way for children to get the best possible treatment.

Robotic chemotherapy compounding: A multicenter productivity approach.

INTRODUCTION: The aim of this study is to compare productivity of the KIRO Oncology compounding robot in three hospital pharmacy departments and identify the key factors to predict and optimize automatic compounding time. METHODS: The study was conducted in three hospitals. Each hospital compounding workload and workflow were analyzed. Data from the robotic compounding cycles from August 2017 to July 2018 were retrospectively obtained. Nine cycle specific parameters and five productivity indicators were analysed in each site. One-to-one differences between hospitals were evaluated. Next, a correlation analysis between cycle specific factors and productivity indicators was conducted; the factors presenting a highest correlation to automatic compounding time were used to develop a multiple regression model (afterwards validated) to predict the automatic compounding time. RESULTS: A total of 2795 cycles (16367 preparations) were analysed. Automatic compounding time showed a relevant positive correlation (ǀrs|>0.40) with the number of preparations, number of vials and total volume per cycle. Therefore, these cycle specific parameters were chosen as independent variables for the mathematical model. Considering cycles lasting 40 minutes or less, predictability of the model was high for all three hospitals (R2:0.81; 0.79; 0.72). CONCLUSION: Workflow differences have a remarkable incidence in the global productivity of the automated process. Total volume dosed for all preparations in a cycle is one of the variables with greater influence in automatic compounding time. Algorithms to predict automatic compounding time can be useful to help users in order to plan the cycles launched in KIRO Oncology.

Costs associated with United States pharmacopeia compliant infusion clinics.

PURPOSE: As costs continue to rise in oncology, a strategy that has been implemented to limit these costs is use of alternative sites of care. However, there are differences in regulatory standards between common sites of care such as freestanding infusion clinics and hospital outpatient departments. The costs associated with United States Pharmacopeia compliance were evaluated in order to better understand the cost of universally compliant hospital outpatient departments. METHODS: Annual operational costs associated with United States Pharmacopeia compliance were estimated for a 30-chair infusion clinic with United States Pharmacopeia <797> and <800> pharmacy cleanrooms for non-hazardous and hazardous drugs, respectively. Annual United States Pharmacopeia compliance costs included: competency assessments, personal protective equipment, closed system transfer devices, labels, cleaning supplies, and environmental monitoring. One-time costs included initial cleanroom construction and renovations. Published information and benchmarks provided baseline assumptions for patient volume, staffing, and unit costs. If no published data was available, prices were estimated based on a similarly sized clinic. RESULTS: Recurring annual costs for a 30-chair fully compliant infusion clinic were calculated to be $785,207. One-time costs associated with initial construction and renovations were estimated to be $1,365,207-$1,535,207 and $965,207-$1,005,207, respectively. CONCLUSIONS: Costs associated with increased operational oversight and regulatory standards are a major contributing factor to the facility fee of hospital outpatient departments. Ultimately, all sites of care share in the goal to provide optimal patient care while considering all aspects of patient care, including cost. Therefore, a move towards consistent regulatory standards across all settings would aid in preventing discrepancies in care.

Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL.

In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5-7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95-105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.

Effect of Drug Compounding on Quality of Life in Patients With Genodermatoses: A Cross-Sectional Study. / Formulación magistral en pacientes con genodermatosis. Impacto en la calidad de vida: un estudio transversal.

BACKGROUND: Cutaneous manifestations are complicated to treat in rare diseases. The main aim of this study was to analyze the impact of compounded drugs prepared by hospital pharmacists on the quality of life of patients with genodermatoses. MATERIAL AND METHODS: We undertook a cross-sectional study of patients with genodermatoses treated with topical medications compounded and dispensed by the pharmacy at Complejo Hospitalario Universitario in Pontevedra, Spain. We collected demographic data and answers to questionnaires examining generic and disease-specific quality of life, treatment satisfaction, and treatment adherence. RESULTS: Nine patients were included. We observed a significant improvement in health-related quality of life following treatment with compounded drugs. Satisfaction with the topical medications was 2.8 on a scale of 0 (greatest satisfaction) to 25. Treatment adherence was 59%. CONCLUSIONS: Drug compounding facilitates access to orphan drugs that are not available for many rare diseases. Few studies, however, have analyzed impact on quality of life in this setting. In this series of patients with genodermatoses, topical medications compounded and dispensed by a hospital pharmacy improved health-related quality of life. This preliminary study has given rise to a multicenter study of compounding for ichthyosis. We expect that analysis of a larger sample will confirm our findings.

Leveraging advanced preparation of oncology medications: Decreasing turnaround-times in an outpatient infusion center.

INTRODUCTION: Many oncology infusions are provided in hospital-based infusion centers. With hospital-based infusion centers seeing increased volumes, patient wait times continue to be a priority. Extended wait times for oncology infusions have been shown to lead to patient dissatisfaction. METHODS: Advanced Preparation of oncology infusion medications allows pharmacy to verify and prepare specific medications the day before a patient's infusion appointment. Our study targeted lower cost, commonly used medications to prepare in advance. Data analyzed included turnaround time (TAT), medication waste, and oncology infusion preparation volumes. Implementation took place in two phases to allow time for the healthcare team to adjust to the new workflow. Phase I medications include a small amount of medications prepared manually by pharmacy technicians. Phase II medications included all phase I medications plus additional medications that were compounded in the intravenous (IV) robotic compounding system. RESULTS: Our study demonstrated significant decrease in median TAT for medications prepared in advance. 537 infusions were prepared using the Advanced Preparation module with a median TAT of 24.2 minutes (IQR, 18.0-34.0). The pre-implementation median TAT was 45.0 minutes (IQR, 36.0-56.0), which represents a decrease of 20.8 minutes (46.2%) following implementation of the program, (p<0.001). There were a total of 149 advanced preparation doses that were wasted (21.7% of doses). CONCLUSION: We have seen a statistically significant reduction in TAT for Advanced Preparation medications. Low volume of Advanced Preparation medications compared to total infusion volume limited impact on overall TAT.

Beyond-Use Dates Assignment for Pharmaceutical Preparations: Example of Low-Dose Amiodarone Capsules.

Background: Beyond-use dates (BUDs) in compounding practice are assigned from stability studies. The United States Pharmacopoeia (USP 42 NF 37) suggested to assign a 6 months BUD for dry oral forms. A new pediatric formula of amiodarone capsules was implemented in our hospital, with 3 dosages (5 mg, 20 mg, and 50 mg). Objective: BUD of these new formulas had to be determined by stability study. Methods: The method for the determination of amiodarone content was validated to be stability indicating, and a stability study was performed. Different excipients commonly used for capsule compounding were compared. Results: We found that, with microcrystalline cellulose as excipient, 50 mg amiodarone capsules were stable for 1 year, whereas 5 mg and 20 mg capsules were not. This difference was studied, and lactose or mannitol were found to be better excipients for 5 mg amiodarone capsules, despite their potential side effects. A potential drug-excipient interaction between microcrystalline cellulose and amiodarone hydrochloride is described. Conclusion: Amiodarone hydrochloride/microcrystalline cellulose capsules have a BUD of 1 month for 5 mg capsules, 6 months for 20 mg, and 1 year for 50 mg.

Optimization of resources by drug management: A multicentred web-administered study on the use of ipilimumab in Italy.

OBJECTIVE: In a scenario of new expensive cancer therapies entering the market, strategies of optimisation and cost containment are crucial in oncology care. Better management of drug waste and centralization of drug preparation can be effective strategies to achieve these goals. The aim of this work is to describe the economic management of a high cost anticancer drug (ipilimumab) in some Italian reference centres. METHODS: This was an observational, multicentred study in which economical and clinical data of 21 cancer centres (418 patients) were collected during the enrollment period from February 2013 to August 2014. The follow-up period ended in July 2015. RESULTS: Participants purchased 10.7% more vials of ipilimumab than necessary for compounding. The results were variable among centres, and only five centres had a deviation lower than 5% between the drug purchased and the drug prescribed. Hospitals applying the drug day reached a statistically significant residual of drug effectively used compared to the amount prescribed (P = 0.018). Consequently, the price for treating a model patient was significantly lower in those hospitals (median spare of 7456 euro per patient). CONCLUSIONS: This study demonstrated that the careful management of drug waste and the application of drug-day, through a proper selection of vial and the ability to use the leftover drug, can generate economic savings. However, tailoring the drug stock to clinical need is still an open issue which deserves further analysis.

Quantitative and qualitative control of antineoplastic preparations: Gravimetry versus HPLC.

This article compares gravimetry vs. high-performance liquid chromatography (HPLC) as quality control (QC) methods for paclitaxel, docetaxel and oxaliplatin preparations. We aimed at assessing the preparation method reliability in our hospital, evaluating compounding accuracy and estimating the influence of personnel training and standardized homogenization on compounding accuracy. Agreement, correlation, concordance, accuracy and precision between methods were evaluated for each drug. Conforming preparation percentages (CPs) at different tolerance limits (TLs) and compounding accuracy were calculated for each method and drug. Compounding accuracy was compared before and after personnel training and standardized homogenization implantation. SPSS v 20.0 and Ene v 2.0 were used. A total of 222 samples (58 docetaxel, 95 paclitaxel and 69 oxaliplatin) were analyzed. Gravimetry and HPLC are comparable methods. Overall CP was 81% for gravimetry at 10% TL and 85% for HPLC at 15% TL. Compounding accuracy is shown to be good for all methods and drugs. Homogenization optimization and personnel training make measurements more accurate for docetaxel and paclitaxel HPLC, but seem to worsen accuracy for docetaxel gravimetry. Gravimetry has shown to be a good alternative to HPLC for routine QC. Coupling with electronic methods should be considered in the future.

Price-Performance Ratio Analysis Of Enteral Vitamin K Formulations.

BACKGROUND: Vitamin K compounded oral solution costs significantly less on a per-milligram basis compared with tablet formulations. Current literature has shown that international normalized ratio (INR) lowering in the reversal of vitamin K antagonists (VKAs) occurs to a similar degree when using vitamin K oral solution compared with tablet formulations. OBJECTIVE: To compare drug spending on vitamin K oral solution versus tablet using a price-performance ratio (PPR). METHODS: A retrospective chart review was conducted at a tertiary care academic medical center to compare INR reversal of VKA-induced coagulopathy on a price basis for vitamin K oral solution versus tablet. The price of the oral solution accounted for supplies and labor. A PPR was calculated based upon the following formula: vitamin K formulation cost divided by the hourly percent change in INR following vitamin K administration. RESULTS: The PPR for vitamin K tablets was 27.0 compared with 5.8 for the oral solution (P = 0.006). CONCLUSIONS: Utilization of vitamin K solution resulted in a significantly reduced cost per INR-lowering effect relative to commercially available tablets. Utilization of a compounded vitamin K solution represents an enticing means of cost-savings in the hospital setting.

Suspended particle and drug ingredient concentrations in hospital dispensaries and implications for pharmacists' working environments.

OBJECTIVES: The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. METHODS: We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. RESULTS: The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. CONCLUSION: On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed.

Evaluating the Sensitivity of a Media-Fill Challenge Test Under Various Situations as a Reliable Method for Recommended Aseptic Technique Competency Assessment.

Background: Microbial contamination of compounded medications is a serious concern within hospital pharmacies as it can lead to severe patient injury. The United States Pharmacopeia <797> mandates that pharmacy personnel responsible for preparing compounded sterile preparations must annually demonstrate competency in aseptic technique by performing a media-fill challenge test. Objective: The purpose of this study is to evaluate the sensitivity of a commonly used media-fill test through proper and improper compounding techniques. Methods: Two aseptically trained pharmacy technicians performed media-fill challenge testing by carrying out 5 separate manipulations 5 times each for a total of 25 trials. Sterile vials, syringes, and intravenous bags were prepared. The first manipulation followed best-practice aseptic technique and sterile compounding procedures. Each of the following 4 manipulations removed one aspect of best-practice aseptic technique. The prepared products were incubated at 20°C to 25°C. A positive result for microbial contamination is indicated by visible turbidity within the vials, syringes, and intravenous bags at the following check points: 24 hours, 72 hours, 7 days, 14 days, 21 days, and >30 days. Results: Twenty-five trials, each containing 10 distinct admixtures, resulted in a total of 250 compounded preparations. No single preparation showed signs of turbidity, sedimentation, or visible microbial growth at any of the 6 checkpoints yielding a 0% contamination rate. However, the positive controls inoculated with bacteria did have positive microbial growth results. Conclusion: A more sensitive test needs to be developed to provide assurances that all poor aseptic practices are detected in compounding personnel.

Economic assessment of aseptic compounding rooms in hospital pharmacies in five European countries.

PURPOSE: The aims of the study are to make an inventory of fixtures of aseptic compounding structures, to compare, using real examples, the design and operating costs of controlled atmosphere area (CAA) with isolators and CAA with laminar flow biological safety cabinets (BSCs) in order to determine the most economical scheme in hospitals and to give a final facilities cost calculated for one workstation. METHODS: Forty-three hospitals were interviewed (21 French and 22 from four European countries) over seven months. Hospital pharmacists completed a form with 390 items. Hospitals are compared according to their workstation type: BSCII or BSCIII (group B) and isolator (group I), using Mann and Whitney's statistical test and Monte-Carlo modeling. RESULTS: Twenty-one hospitals responded (11 French and 10 from other European countries). All European compounding unit organizations are not significantly different. The study compared items such as infrastructure cost, equipment cost, staff cost, consumable cost, cleaning cost and control cost. A synthesis of all costs has been drafted to calculate an estimated preparation cost which seemed to be higher for group B than for group I when staff costs were included ($46 and $31, respectively, in study conditions). CONCLUSIONS: The different costs studied have revealed little significant difference between group B and I. The preparation cost in group B appears higher than in group I. This pilot study has resulted in the calculation of an estimated manufactured preparation cost but this work should be completed to help optimize resources and save money.

Evaluation of ultraviolet irradiation efficacy in an automated system for the aseptic compounding using challenge test.

OBJECTIVE: Ultraviolet (UV) irradiation efficacy in the intravenous compounding robot APOTECAchemo was evaluated to define the best operative conditions in terms of sterility and time optimization. DESIGN: The challenge test was used against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis spores and Candida albicans. Inoculated plates were placed inside the robot and irradiated for different times. Microbial air and surface quality inside the equipment were monitored utilizing settle and contact plates, swabs. RESULTS: After 4 h, no microorganisms were viable with killing rates ranging from 5- to 7-log for different microorganisms after 1 h of exposition. In confirmation of the efficacy of the UV irradiation program adopted, the microbial monitoring inside the equipment always gave negative results. CONCLUSIONS: This is the first exhaustive investigation of UV irradiation efficacy in the aseptic pharmaceutical production. We demonstrated that UV irradiation plays an essential role in maintaining the sterility condition of the workplace inside the APOTECAchemo and assuring the standards for aseptic manufacturing of medicinal drugs, as required for Class A clean areas. A 4-h UV irradiation also ensures sterility in the case of very resistant microorganisms and in the presence of high microbial charge (10(8) CFU/ml), but a killing rate of 5 or more is already recorded after the first hour of exposition. The results provide useful information for the best operative conditions in terms of both sterility and time optimization, not only for the automated compounding, but also for the traditional aseptic manufacturing processes.

Formulation and stability of an extemporaneous 0.02% chlorhexidine digluconate ophthalmic solution.

BACKGROUND/PURPOSE: Acanthamoeba keratitis is difficult to treat because Acanthamoeba cysts are resistant to the majority of antimicrobial agents. Despite the efficacy of 0.02% chlorhexidine in treating Acanthamoeba keratitis, a lack of data in the literature regarding the formulation's stability limits its clinical use. The objective of this study was to develop an optimal extemporaneous 0.02% chlorhexidine digluconate ophthalmic formulation for patients in need. METHODS: With available active pharmaceutical ingredients, 0.02% chlorhexidine digluconate sample solutions were prepared by diluting with BSS Plus Solution or acetate buffer. Influences of the buffer, type of container, and temperature under daily-open condition were assessed based on the changes of pH values and chlorhexidine concentrations of the test samples weekly. To determine the beyond-use date, the optimal samples were stored at 2-8°C or room temperature, and analyzed at time 0 and at Week 1, Week 2, Week 3, Week 4, Week 5, Week 8, Week 12, and Week 24. RESULTS: Despite chlorhexidine exhibiting better stability in acetate buffer than in BSS solution, its shelf-life was < 14 days when stored in a light-resistant low-density polyethylene container. The acetate-buffered 0.02% chlorhexidine digluconate solution stored in light-resistant high-density polyethylene eyedroppers did not exhibit significant changes in pH or strength at any time interval. CONCLUSION: The acetate-buffered 0.02% chlorhexidine digluconate ophthalmic solution stored in light-resistant high-density polyethylene eyedroppers demonstrated excellent stability at 2-25°C for 6 months after being sealed and for 1 month after opening. This finding will enable us to prepare 0.02% chlorhexidine digluconate ophthalmic solutions based on a doctor's prescription.

The FDA Funding Crisis.

The role of the Food and Drug Administration (FDA) is to ensure the safety of prescription and nonprescription drugs, dietary supplements, and the food supply, representing more than 20% of US consumer spending. The increased need to monitor imported drugs, drug products and foods, drug shortages, and compounding pharmacies bring the adequacy of FDA funding into question. Performing even at status quo cannot be accomplished if responsibilities increase without equitable funding increases: both from the federal government and fees imposed on FDA-regulated industries. Additionally, scientific advancement, new legislation, and new industries are continually increasing the FDA workload, necessitating commensurate budget increases.

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.

Formulation and Stability of a 1% Clarithromycin-Based Topical Skin Cream: A New Option to Treat Buruli Ulcers?

There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by Mycobacterium ulcerans, which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections.