Development and Validation of Matrix of Chemistry, Manufacturing, and Control (MoCMC) System for Intramammary Drug Products (IMM).

PURPOSE: Products formulated for intramammary (IMM) infusion are intended for the delivery of therapeutic moieties directly into the udder through the teat canal to maximize drug exposure at the targeted clinical site, the mammary gland, with little to no systemic drug exposure. Currently, to our knowledge, there has been no in-vitro matrix system available to differentiate between IMM formulations. Our goal is to develop A custom tailored in-vitro "Matrix of Chemistry, Manufacturing and Control" (MoCMC) System to be a promising future tool for identifying inequivalent IMM formulations. MoCMC can detect inter and intra batch variabilities, thereby identifying potential generics versus brand product similarities or differences with a single numeric value and a specific & distinctive fingerprint. METHODS: The FDA-approved IMM formulation, SPECTRAMASTⓇ LC, was selected as the reference product for the MoCMC. Twelve in-house test formulations containing ceftiofur hydrochloride were formulated and characterized. The MoCMC was developed to include six input parameters and three output parameters. The MoCMC system was used to evaluate and compare SPECTRAMASTⓇ LC with its in-house formulations. RESULTS: Based on the MoCMC generated parameters, the distinctive fingerprints of MoCMC for each IMM formulations, and the statistical analyses of MCI and PPI values, in-house formulations, F-01 and F-02 showed consistency while the rest of in-house formulations (F-03-F-12) were significantly different as compared to SPECTRAMASTⓇ LC. CONCLUSION: This research showed that the MoCMC approach can be used as a tool for intra batch variabilities, generics versus brand products comparisons, post-approval formulations changes, manufacturing changes, and formulation variabilities.

Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product.

PURPOSE: Intramammary (IMM) formulations are locally acting and delivered intracisternally into the udder. No pharmacopeial in-vitro release method is available to differentiate between the IMM formulations. Our research aim is to develop in-vitro release methods that discriminate different IMM formulations (SPECTRAMAST® LC and in-house formulations). METHODOLOGY: Different in-house formulations were developed to simulate SPECTRAMAST® LC generics. SPECTRAMAST® LC and the in-house formulations were characterized for physicochemical attributes, such as particle size, rheology, drug content, sedimentation rate, and flocculation rate. The in-vitro release method was optimized by evaluating drug release using USP apparatuses 1, 2 (with and without enhancer/customized cells), and 4. Various test parameters, including medium effect (whole homogenized bovine milk versus aqueous buffer), medium volume (200-900 mL), and rotational speed (50-200 rpm) were investigated. RESULTS: Two potential in-vitro systems can be used as discriminatory methods for IMM formulations: USP apparatus 2 with the IMM formulation loaded into two containers a) customized formulation container (83.1 cm in height and 56.4 cm in width) or b) enhancer cells with their top adapted with mesh #40 (rotation speed:125 rpm and 900 mL of whole homogenized bovine milk). The release profile of SPECTRAMAST® LC at 1 h (99.8%) was not significantly different from formulations with similar physicochemical characteristics F-01 (99.1%) and F-02 (100.5%). Formulation with different physicochemical characteristics F-03 (44.3%) and F-04 (57.2%) showed slower release (1 h) than SPECTRAMAST® LC (98.8%). CONCLUSION: The developed in-vitro release methods can be used as a potential tool for in-vitro comparability evaluations for IMM formulations.

Posaconazole versus voriconazole as antifungal prophylaxis for invasive fungal diseases in patients with hematological malignancies.

INTRODUCTION: The incidence of invasive fungal diseases (IFDs) has risen in hematologic malignancy patients due to neutropenia. While posaconazole is recommended as the first-line antifungal prophylaxis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients and voriconazole is an alternative, there is currently no direct comparison data available to assess their relative effectiveness. METHOD: We retrospectively reviewed eligible patient charts from January 2017 to February 2019 to identify breakthrough IFD rates, drug adverse event frequency, and drug acquisition cost in AML/MDS patients. RESULTS: Forty-eight patients received 130 chemo cycles, with 50 (38%) cycles prescribed posaconazole and 80 (62%) prescribed voriconazole as primary IFD prophylaxis. The incidence rates of IFD in the posaconazole group were 8% (4 out of 50), of which two were probable and two were possible infections, while 6.26% (5 out of 80) of patients in the voriconazole group developed IFD, with four possible infections and one probable infection (p = 0.73). A higher percentage of patients in the voriconazole group discontinued prophylaxis due to adverse events, with six patients compared to two patients in the posaconazole group (p = 0.15). The drug acquisition cost of posaconazole is 5.62 times more expensive than voriconazole. CONCLUSION: The use of voriconazole instead of posaconazole for 130 chemo cycles would save $166,584.6. Posaconazole and voriconazole have comparable efficacy and safety in preventing IFD in AML and MDS patients receiving chemotherapy. However, posaconazole is more costly than voriconazole.

Bioavailability assessment of a brompheniramine taste-masked pediatric formulation in a juvenile porcine model.

A brompheniramine taste-masked pediatric formulation was developed as part of the National Institutes of Health Pediatric Formulation Initiative to help address low patient compliance caused by the bitter taste of many adult formulations. To confirm that the taste-masked formulation can provide a similar pharmacological effect to the previous marketed adult formulations, a juvenile porcine model was used to screen the model pediatric formulation to compare the bioavailability between the marketed brompheniramine maleate and the taste-masked maleate/tannate formulation. Pigs were dosed orally with both formulations and blood samples were obtained from 0 to 48 h. Plasma samples were prepared and extracted using solid-phase extraction. The mass spectrometer was operated under selected ion monitoring mode. The selected ion monitoring channels were set to m/z 319.1 for brompheniramine and m/z 275.2 for the internal standard chlorpheniramine. Calibration curves were linear over the analytical range 0.2-20 ng/ml (r2 > 0.995) for brompheniramine in plasma. The intra- and inter-day accuracies were between 98.0 and 105% with 5.73% RSD precision. The bioanalytical method was successfully applied to a preclinical bioavailability study. The bioavailability profiles were not significantly different between the two formulations, which demonstrates that taste-masking with tannic acid is a promising approach for formulation modification for pediatric patients.

International registry on aortic balloon occlusion in major trauma: Partial inflation does not improve outcomes in abdominal trauma.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a method for temporary hemorrhage control used in haemodynamically unwell patients with severe bleeding. In haemodynamically unwell abdominal trauma patients, laparotomy remains the initial procedure of choice. Using REBOA in patients as a bridge to laparotomy is a novel option whose feasibility and efficacy remain unclear. We aimed to assess the clinical outcome in patients with abdominal injury who underwent both REBOA placement and laparotomy. METHODS: This is a retrospective study, including trauma patients with an isolated abdominal injury who underwent both REBOA placement and laparotomy, during the period 2011-2019. All data were collected via the Aortic Balloon Occlusion Trauma Registry database. RESULTS: One hundred and three patients were included in this study. The main mechanism of trauma was blunt injury (62.1%) and the median injury severity score (ISS) was 33 (14-74). Renal failure and multi-organ dysfunction syndrome (MODS) occurred in 15.5% and 35% of patients, respectively. Overall, 30-day mortality was 50.5%. Post balloon inflation systolic blood pressure (SBP) >80 mmHg was associated with lower 24-h mortality (p = 0.007). No differences in mortality were found among patients who underwent partial occlusion vs. total occlusion of the aorta. CONCLUSIONS: Our results support the feasibility of REBOA use in patients with isolated abdominal injury, with survival rates similar to previous reports for haemodynamically unstable abdominal trauma patients. Post-balloon inflation SBP >80 mmHg was associated with a significant reduction in 24-h mortality rates, but not 30-day mortality. Total aortic occlusion was not associated with increased mortality, MODS, and complication rates compared with partial occlusion.

Patient In-Use Stability Testing of FDA-Approved Metformin Combination Products for N-Nitrosamine Impurity.

Between February 2020 and January 2022, the Food and Drug Administration (FDA) recalled 281 metformin extended-release products due to the presence of N-nitrosodimethylamine (NDMA) above the acceptable daily intake (ADI, 96 ng/day). Our previous studies indicated presence of NDMA levels above ADI in both metformin immediate and extended-release products. When metformin products have NDMA impurities, it is indispensable to check for the same impurities in metformin combination products. Therefore, the objective of the present study was to evaluate in-use stability of commercial metformin combination products for NDMA. For this purpose, metformin products in combination with glyburide (GB1-GB12), glipizide (GP1-GP8), pioglitazone (P1-P3), alogliptin (A1, A2), and linagliptin (L1, L2) were repacked in pharmacy vials, stored at 30°C/75% RH for 3 months, and monitored for NDMA impurity. The NDMA level varied from 0 to 156.8 ± 32.8 ng/tablet initially and increased to 25.4 ± 5.1 to 455.0 ± 28.4 ng/tablet after 3 months of exposure to in-use condition. Initially, 18 products have NDMA level below ADI limit before exposure which decreased to 7 products (GB5, GP3, GP5, A1, A2, L1, and L2) meeting specification. In conclusion, in-use stability study provides quality and safety risk assessment of drug products where nitroso impurities are detected in the probable condition of use.

In Vitro and In Vivo testing of 3D-Printed Amorphous Lopinavir Printlets by Selective Laser Sinitering: Improved Bioavailability of a Poorly Soluble Drug.

The aim of this paper was to investigate the effects of formulation parameters on the physicochemical and pharmacokinetic (PK) behavior of amorphous printlets of lopinavir (LPV) manufactured by selective laser sintering 3D printing method (SLS). The formulation variables investigated were disintegrants (magnesium aluminum silicate at 5-10%, microcrystalline cellulose at 10-20%) and the polymer (Kollicoat® IR at 42-57%), while keeping printing parameters constant. Differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared analysis confirmed the transformation of the crystalline drug into an amorphous form. A direct correlation was found between the disintegrant concentration and dissolution. The dissolved drug ranged from 71.1 ± 5.7% to 99.3 ± 2.7% within 120 min. A comparative PK study in rabbits showed significant differences in the rate and extent of absorption between printlets and compressed tablets. The values for Tmax, Cmax, and AUC were 4 times faster, and 2.5 and 1.7 times higher in the printlets compared to the compressed tablets, respectively. In conclusion, the SLS printing method can be used to create an amorphous delivery system through a single continuous process.

Reconstruction of soft tissue defects of hand: A systematic approach.

Background and Objective: A thorough insight into the management of hand injuries can shape the approach of a surgeon in order to achieve optimal outcomes for the patients. The aim of this study was to share our experience in reconstruction of the hand and establishing an algorithm for classification and treatment of hand injuries. Methods: This is a descriptive cross sectional study and was conducted from January 2020 to August 2022 at Burns and Plastic Surgery center, Peshawar. Data was collected from medical records about the patient demographics, mechanism of injury and type of procedures done. Defect size was classified into small (<5cm), medium (5cm to 10 cm) and large (>10cm). The defect site and size was cross tabulated against the method of soft tissue reconstruction in order to make the algorithm for reconstruction of hand injuries. Data was analyzed using SPSS. Results: The study population included 41 (75.9%) male and 13 (24.1%) female patients, mean age 31.56±14.1. Machine injuries (33.3%) and electric burns (24.1%) were the most common cause of hand soft tissue defects. The most commonly performed flap was Posterior introsseous artery (PIA) flap, followed by First dorsal metacarpal artery (FDMA) flap. Flap necrosis was observed in three cases (5.6%). Conclusion: This treatment algorithm for coverage of soft tissue defects in hand injuries will help with the decision making process of hand reconstruction and has didactic value for novice surgeons. It will also form the foundation for further work on this aspect of hand injuries.

In-person radiologist to review the trauma panscan: a high-fidelity simulation training program for radiology trainees at an academic level 1 trauma center.

BACKGROUND: Radiology trainees were uncomfortable going to the CT scanner to review trauma panscans and interacting with trauma surgeons. OBJECTIVE: This study aims to determine if radiology residents can be trained to accurately identify injuries requiring immediate surgical attention at the CT scanner. METHODS: A high-fidelity simulation model was created to provide an immersive training experience. Between February 2015 and April 2017, 62 class 1 trauma panscans were read at the CT scanner by 11 PGY-3 radiology residents. Findings made at the scanner were compared to resident preliminary and attending radiology reports and correlated with clinical outcomes. Timestamps were recorded and analyzed. Surveys were administered to assess the impact of training on radiology residents' self-confidence and to assess trauma surgeons' preference for radiology at the scanner. Significance level was set at p < 0.05. RESULTS: The mean time to provide results at the CT scanner was 11.1 min. Mean time for the preliminary report for CT head and cervical spine was 24.4 ± 9.8 min, and for the CT chest, abdomen, and pelvis was 16.3 ± 6.9 min. 53 traumatic findings on 62 panscans were identified at the scanner and confirmed at preliminary and final reports, for a concordance rate of 85%, compared to 72% for the control group. Radiology residents agreed or strongly agreed the training prepared them for trauma panscan reporting. Trauma surgeons shifted in favor of radiology presence at the scanner. CONCLUSION: Radiology residents can be trained to accurately and rapidly identify injuries requiring immediate surgical attention at the CT scanner. CLINICAL IMPACT: These findings support the value-added of an in-person radiologist at the CT scanner for whole-body trauma panscans to facilitate timely detection of life-threatening injuries and improve professional relations between radiologists and trauma surgeons.

Co-Doped CeO2/Activated C Nanocomposite Functionalized with Ionic Liquid for Colorimetric Biosensing of H2O2 via Peroxidase Mimicking.

Hydrogen peroxide acts as a byproduct of oxidative metabolism, and oxidative stress caused by its excess amount, causes different types of cancer. Thus, fast and cost-friendly analytical methods need to be developed for H2O2. Ionic liquid (IL)-coated cobalt (Co)-doped cerium oxide (CeO2)/activated carbon (C) nanocomposite has been used to assess the peroxidase-like activity for the colorimetric detection of H2O2. Both activated C and IL have a synergistic effect on the electrical conductivity of the nanocomposites to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The Co-doped CeO2/activated C nanocomposite has been synthesized by the co-precipitation method and characterized by UV-Vis spectrophotometry, FTIR, SEM, EDX, Raman spectroscopy, and XRD. The prepared nanocomposite was functionalized with IL to avoid agglomeration. H2O2 concentration, incubation time, pH, TMB concentration, and quantity of the capped nanocomposite were tuned. The proposed sensing probe gave a limit of detection of 1.3 × 10-8 M, a limit of quantification of 1.4 × 10-8 M, and an R2 of 0.999. The sensor gave a colorimetric response within 2 min at pH 6 at room temperature. The co-existing species did not show any interference during the sensing probe. The proposed sensor showed high sensitivity and selectivity and was used to detect H2O2 in cancer patients' urine samples.

Nitroso Impurities in Drug Products: An Overview of Risk Assessment, Regulatory Milieu, and Control Strategy.

Many nitrosamines have been recognized to be carcinogenic for many decades. Despite the fact that several nitrosamine precursors are frequently used in the manufacturing of pharmaceutical products, their potential presence in pharmaceutical products has previously been overlooked due to a lack of understanding on how they form during the manufacturing process. From the risk assessment, it is clear that nitrosamines or their precursors may be present in any component of the finished dosage form. As a risk mitigation strategy, components with a high potential to form nitrosamine should be avoided. In the absence of suitable alternatives, sufficient measures to maintain nitrosamines below acceptable intake levels must be applied. Excipient manufacturing pathways must be extensively studied in order to identify probable excipient components that may contribute to nitrosamine formation. The manufacturers must not solely rely on pharmacopeial specifications for APIs and excipients, rather, they should also develop and implement additional strategies to control nitrosamine impurities. The formulation can be supplemented with nitrosating inhibitors, such as vitamin C, to stop the generation of nitrosamine. The purpose of this review is to identify key risk factors with regard to nitrosamine formation in pharmaceutical dosage forms and provide an effective control strategy to contain them below acceptable daily intake limits.

Preparation and Characterization of 3D-Printed Dose-Flexible Printlets of Tenofovir Disoproxil Fumarate.

The aim of this work was to design pediatric-friendly, dose-flexible orally disintegrating drug delivery systems (printlets) of the antiviral drug tenofovir disoproxil fumarate (TDF) by selective laser sintering (SLS) for potential use in hospitals along with other antiviral drugs. In order to obtain a consistent quality of printlets with desired properties, it is important to understand certain critical quality attributes for their main and interactions effect. The printlets were optimized by Box-Behnken's design of the experiment by varying process variables while keeping the composition constant. The composition contained 16.3% TDF, 72.7% polyvinyl pyrrolidone K16-18, 8% magnesium aluminum silicate, 3% Candurin® NXT Ruby Red, and 0.3% colloidal silicon dioxide. The process variables studied were surface (X1), chamber temperatures (X2), and laser scanning speed (X3). The range of variable levels was 75-85°C for X1, 50-70°C for X2, and 200-240 mm/s for X3, respectively. The responses studied were hardness, disintegration time, dissolution, physiochemical, and pharmacokinetic characterization. X-ray powder diffraction indicated partial or complete conversion of the crystalline drug into amorphous form in the printlets. Comparative pharmacokinetics between Viread® (generic) and printlets in rats were superimposable. Pharmacokinetic parameters showed statistically insignificant differences between the two formulations in terms of Tmax, Cmax, and AUC of (p > 0.05). Printlets were bioequivalent to Viread® as per FDA bioequivalence criteria. Thus, the SLS printing method showed the fabrication of dose-flexible printlets with quality, and in vivo performance equivalent to commercial tablets.

An Institutional Guide for Formulary Decisions of Biosimilars.

Biologics have changed the landscape for the management of many debilitating chronic diseases but account for a significant expenditure of medications globally. Fortunately, advances in technology paved the way for the introduction of biosimilars, which are highly similar to the originator biologics. In the quest to reduce the budget impact of biologics, organizations have begun to adopt biosimilars. Institutions evaluating biosimilars for inclusion in the hospital formulary must make informed formulary decisions by conducting a thorough review of key elements for evaluation of biosimilars and address the multidimensional aspects during the selection process of different biosimilar products. Therefore, we aim to present an institutional guide of these elements to inform formulary decisions. These key elements include biosimilar evaluation for formulary addition; regulatory approval; substitution, interchangeability, and switching; extrapolation; product characteristics, manufacturing, and supply chain issues; pharmacoeconomic evaluations; traceability, nomenclature, and coding; education; and pharmacovigilance.

Very-Rapidly Dissolving Printlets of Isoniazid Manufactured by SLS 3D Printing: In Vitro and In Vivo Characterization.

The focus of this research was to understand the effects of formulation and processing variables on the very-rapidly dissolving printlets of isoniazid (INH) manufactured by the selective laser sintering (SLS) three-dimensional (3D) printing method, and to characterize their physicochemical properties, stability, and pharmacokinetics. Fifteen printlet formulations were manufactured by varying the laser scanning speed (400-500 mm/s, X1), surface temperature (100-110 °C, X2), and croscarmellose sodium (CCS, %, X3), and the responses measured were weight (Y1), hardness (Y2), disintegration time (DT, Y3), and dissolution (Y4). Laser scanning was the most important processing factor affecting the responses. DT was very rapid (≥3 s), and dissolution (>99%) was completed within 3 min. The root-mean-square error in the studied responses was low and analysis of variance (ANOVA) was statistically significant (p < 0.05). X-ray micro-computed tomography (micro-CT) images showed very porous structures with 24.6-34.4% porosity. X-ray powder diffraction and differential scanning calorimetry data indicated partial conversion of the crystalline drug into an amorphous form. The printlets were stable at 40 °C/75% RH with no significant changes in assay and dissolution. Pharmacokinetic profiles of the printlets and compressed tablets were superimposable. In conclusion, the rapidly dissolving printlets of the INH were stable, and oral bioavailability was similar to that of compositionally identical compressed tablets.

Photocatalytic assessed adsorptive removal of tinidazole from aqueous environment using reduced magnetic graphene oxide-bismuth oxychloride and its silver composite.

Antibiotics (tinidazole (TNZ)) in wastewater, exhibit adverse effects on humans and ecosystem. The current study was aimed to synthesize photocatalysts mrGO/BiOCl and mrGO/BiOCl/Ag. mrGO was coupled with BiOCl by hydrothermal method and Ag was deposited over it. The synthesized mrGO/BiOCl and mrGO/BiOCl/Ag were confirmed by Pzc analysis (5.5 and 4.4 for mrGO/BiOCl and mrGO/BiOCl/Ag, respectively), surface area analysis (380 m2 g-1, 227.7 m2 g-1, 220 m2 g-1 for mrGO, mrGO/BiOCl and mrGO/BiOCl/Ag respectively), elemental analysis (Ag, O, Bi, Fe), surface morphology (rough ball like sphere of mrGO/BiOCl and cubic Ag nanoparticles in mrGO/BiOCl/Ag), functional groups and band gap (Eg) determination. The Eg was determined using Kubelka-Munk equation as 3.5 and 2.8 eV for mrGO/BiOCl and mrGO/BiOCl/Ag respectively. During the adsorption study, the best experimental conditions for various operating parameters such as pH (2), contact time (5 min for mrGO/BiOCl and 10 min for mrGO/BiOCl/Ag under UV irradiation), TNZ concentration (18 µgL-1) and catalyst dosage (0.001 g) were achieved. Kinetic study revealed that both composites followed pseudo second order kinetics (R2 = 0.9979 and 0.9986, respectively). Data of rGO/BiOCl was fitted to Freundlich adsorption model (R2 = 0.9687) and rGO/BiOCl/Ag fitted to Langmuir adsorption model (R2 = 0.9994). Moreover, thermodynamic parameters confirmed that a photodegradation phenomenon was spontaneous and exothermic. The results confirmed that rGO/BiOCl and rGO/BiOCl/Ag are appropriate composites for TNZ removal from the aqueous environment with removal efficiency of 97 and 24%, respectively.

HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation.

Astrocytes are the primary regulator of energy metabolism in the central nervous system (CNS), and impairment of astrocyte's energy resource may trigger neurodegeneration. HIV infections and cocaine use are known to alter epigenetic modification, including miRNAs, which can target gene expression post-transcriptionally. However, miRNA-mediated astrocyte energy metabolism has not been delineated in HIV infection and cocaine abuse. Using next-generation sequencing (NGS), we identified a total of 1900 miRNAs, 64 were upregulated and 68 miRNAs were downregulated in the astrocytes by HIV-1 Tat with cocaine exposure. Moreover, miR-4727-3p, miR-5189-5p, miR-5090, and miR-6810-5p expressions were significantly impacted, and their gene targets were identified as VAMP2, NFIB, PPM1H, MEIS1, and PSD93 through the bioinformatic approach. In addition, the astrocytes treated with the nootropic drug piracetam protects these miRNAs. These findings provide evidence that the miRNAs in the astrocytes may be a potential biomarker and therapeutic target for HIV and cocaine abuse-induced neurodegeneration.

Supramolecular solvent-based liquid phase extraction of antimony prior to spectrophotometric quantification.

Antimony (Sb) is highly hazardous to human health even in minute concentration. Therefore, its accurate and precise determination in the real environmental samples is of immense importance. In this work for the first time, UV-Vis spectrophotometric method was developed for the quantification of Sb(III) from water samples using supramolecular solvent (undecanol-tetrahydrofuran)-based extraction. The maximum absorption wavelength for antomony-diathizone complex was found to be 590 nm having molar absorptivity of 3.1 × 104 L.mol.cm-1. Factors affecting extraction efficiency like solution sample volume, amount of chelating agent, pH, matrix effect, and type and volume of supramolecular solvent were determined and optimized. Analytical parameters like limit of detection (0.19 µg L-1), limit of quantification (0.62 µg L-1), pre-concentration factor (15), enhancement factor (15), and relative standard deviation for 8 successive analysis (0.8%) were calculated under optimized experimental conditions. The method was applied to real water samples like tap water of laboratory, waste water from Kohat hospitals, and dam water (Tanda dam Kohat) with quantitative addition recovery (94-100%).

Wound closure after total knee replacement: Comparison between staples and sutures.

Background and Objective: Total Knee Arthroplasty is a commonly performed procedure for arthritic knees. Preventing complications is of utmost importance for good functional outcomes and preventing morbidity. Wound closure after the procedure is as important as the replacement aspect of surgery.The objective of this study was to provide subjective and objective evidence of better closure technique and material; we conducted the study so that the outcome of TKA can be further improved. Methods: We conducted a randomized trial at The Indus Hospital, Karachi, from December 2018 to June 2020. All patients from age 40 to 70 years who underwent total knee arthroplasty were included in the study. The wound of one knee was closed with Polypropylene (Prolene) sutures, and the other with staples. The wound was assessed independently by two assessors using Hollander's score; lower score means a worse outcome. All data was entered and analyzed using STATA version 16. Results: Thirty patients who underwent bilateral total knee replacement were included in the analysis, among which 71.8% were female. The average age of participants was 57.3 (± 7.5) years. The mean incision length on the right knee was 17.6 ± 1.1 cm, while on the left the incision length was 18.3 ± 1.2 cm. Overall, the mean Hollander score was significantly different among participants in the sutures and staples group in both the right (p-value=0.001) and left knees (p-value=0.001). The score was significantly higher in knees closed with sutures as compared to staples. Also, the mean Hollander score is significantly higher in females than males in both the right knee (B=0.56, p-value=0.049) and the left knee (B=0.38, p-value=0.044). Conclusion: The study has shown that Hollander's score was significantly higher in knees closed with sutures as compared to the patients in whom staples were used for wound closure.

Extremity Tourniquet Training at High Seas.

BACKGROUND: Future navy officers require unique training for emergency medical response in the isolated maritime environment. The authors issued a workshop on extremity bleeding control, using four different commercial extremity tourniquets onboard a training sail ship. The purposes were to assess participants' perceptions of this educational experience and evaluate self-application simplicity while navigating on high seas. METHODS: A descriptive observational study was conducted as part of a workshop issued to volunteer training officers. A post-workshop survey collected their perceptions about the workshops' content usefulness and adequacy, tourniquet safety, self-application simplicity, and device preference. Tourniquet preference was measured by frequency count while the rest of the studied variables on a one-to-ten Likert scale. Frequencies and percentages were calculated for the studied variables, and application simplicity means compared using the ANOVA test (p < 0.05). RESULTS: Fifty-one Spanish training naval officers, aged 20 or 21, perceived high sea workshop content's usefulness, adequacy, and safety level at 8.6/10, 8.7/10, and 7.5/10, respectively. As for application simplicity, CAT and SAM-XT were rated equally with a mean of 8.5, followed by SWAT (7.9) and RATS (6.9), this one statistically different from the rest (p < 0.01). Windlass types were preferred by 94%. CONCLUSIONS: The training sail ship's extremity bleeding control workshop was perceived as useful and its content adequate by the participating midshipmen. Windlass types were regarded as easier to apply than elastic counterparts. They were also preferred by nine out of every ten participants.

Evaluation of handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home setting in the Princess Noorah Oncology Center.

BACKGROUD: Oral medications are commonly prescribed for many cancer patients. Unfortunately, most of them are dispensed without proper counseling about handling practices. We aimed to evaluate the handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home. METHODS: A cross-sectional questionnaire was filled in by adult cancer patients or caregivers who received oral anticancers and/or visited an outpatient pharmacy over two months. RESULTS: A total of 201 participants were interviewed, 67% were female, and nearly 44% were between 40 and 60 years of age. The majority of participants were educated (78%). The top five medications involved were: tamoxifen, capecitabine, letrozole, dasatinib, and imatinib. More than 95% of participants reported that medications were kept away from children and pets in the original container and stored away from extreme heat, cold, and humidity. Hand washing and wearing gloves were not consistently practiced. Only 5% reported "Always" wearing gloves, while 24% reported "Always" washing hands after handling anticancer medications. The participants reported that they had been informed about safe handling and storage by their physician (39%) and pharmacist (25%), while 34% had not been informed. In terms of disposal practices, 66% of patients have not had any unused or expired medications, 29% disposed them in the trash, and 27% returned them. CONCLUSIONS: Our findings suggest that patients and caregivers' handling practices of oral anticancer medications are inconsistent with the published recommendations. Hence, appropriate and comprehensive education is needed to mitigate the risk of exposure to these agents in the home setting.