Specialized educational program for high-grade liver injury management: a three-dimensional printed model approach.

PURPOSE: The study aims to present a specialized educational program using a 3D printed model for managing Grade IV and V liver injuries. Hepatic packing, a common technique, may not always achieve sufficient hemostasis in these cases, warranting alternative solutions such as mesh liver wrapping. However, mastering this procedure is challenging due to limited teaching resources and the need for repeated practice. METHODS: A computer-based model was created from an abdominal CT scan to produce a real-sized injured liver model using thermoplastic elastomer TPU-95. Trainees received systematic instruction from an instructor, allowing them to perform the procedure under supervision and independently. RESULTS: Eight surgical residents at Hillel Yaffe Medical Center participated in the program, with the majority successfully completing the procedure under supervision. Furthermore, trainees demonstrated reduced procedure times when performing independently, indicating improved proficiency. CONCLUSION: This educational approach offers a simple and repeatable method for continuous training in managing high-grade liver injuries, holding potential for enhanced patient outcomes.

Rare craniofacial clefts: Surgical management protocols.

BACKGROUND: Standardization of surgical protocols is an evolving issue owing to the low incidence of rare craniofacial clefts. In this article, we present our surgical management technique for repair of rare craniofacial clefts and evaluate the postoperative results. METHODS: This study was conducted from 2013 to 2022 and included patients who presented with craniofacial clefts. The results were assessed based on parents' satisfaction and objective evaluations by two independent observers. RESULTS: A total of 3679 patients presented with cleft anomalies; of these, 61 patients with 89 rare craniofacial clefts were observed with a prevalence of 2.42/100. The male to female ratio was 1:1.35. Craniofacial cleft "4" and "5" were the most common, with 17 (19.1%) and 16 (17.98%) patients, respectively. Multiple craniofacial clefts were observed in 37.7% of the patients. Associated craniofacial anomalies were found in 39.34% of the patients. The parents of 71.6% of the patients were very satisfied with the results. Based on the scores of two independent observers, 70.27% of the patients showed good results. CONCLUSION: The rare nature of craniofacial clefts and involvement of various structures make the standardization of surgical procedures very challenging. Our experience with these clefts will help new surgeons both in didactics and in technical aspects of patient management. KEY POINTS: 1. We share our experience with rare craniofacial clefts. 2. Each cleft presents with its own unique reconstructive challenges. The literature describes many techniques for each type of cleft, all with multiple permutations. We present a simplified technique that has worked for us over the years for all Tessier clefts.

Exploring the potential of surface-modified alginate beads for catalytic removal of environmental pollutants and hydrogen gas generation.

In this study, hydrogel beads were fabricated using alginate (Algt) polymer containing dispersed nickel phthalocyanine (NTC) nanomaterial. The viscous solution of Algt and NTC was poured dropwise into a divalent Ca2+ ions, resulting in the formation of hydrogel beads known as NTC@Algt-BDs. The surface of the NTC@Algt-BDs was further modified by coating them with different types of metal ions, yielding metal-coated M+/NTC@Algt-BDs. The adsorbed metal ions i.e., Cu+2, Ag+, Ni+2, Co+2, and Fe+3 were subsequently reduced to zero-valent metal nanoparticles (M0) by NaBH4. The prepared beads were characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Initially, M0/NTC@Algt-BDs were examined for the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). Among them, Cu0/NTC@Algt-BDs catalyst exhibited the highest reduction rate and therefore, investigated for reduction of different nitrophenols (NPs) and dyes, including 2-nitrophenol (2-NP), 2,6-dinitrophenol (2,6-DNP), methyl orange (MO), potassium ferrocyanide (PFC), congo red (CR), and acridine orange (ArO). The highest reduction rates of 2.019 and 1.394 min-1 were observed for MO and 2-NP, respectively. Furthermore, the fabricated catalysts were employed for the efficient production of H2 gas by NaBH4 methanolysis. Among which the Ag0/NTC@Algt-BDs catalyst showed excellent catalytic production of H2 gas, exhibiting the lowest activation energy (Ea) of 25.169 kJ/mol at ambient temperature. Furthermore, the impact of NaBH4 amount, and catalyst dosage on the reduction of 2-NP and H2 gas production was conducted whereas the effect of temperature on methanolysis of NaBH4 for evolution of H2 gas was studied. The amount of H2 gas was confirmed by GC-TCD system. Additionally, the recyclability of the catalyst was investigated, as it garnered significant research interest.

Novel Textbook Outcomes following emergency laparotomy: Delphi exercise.

BACKGROUND: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. METHODS: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1-5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. RESULTS: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into 'early' and 'longer-term'. For non-trauma patients the proposed early Textbook Outcome was 'Discharged from hospital without serious postoperative complications (Clavien-Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was 'Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien-Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)'. The longer-term Textbook Outcome for both non-trauma and trauma was 'Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year'. CONCLUSION: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.

A Systematic Review and Meta-Analysis of the Management of Gallstone Cholecystitis and Common Biliary Duct Stones to Reduce the Incidence of Complications in Elderly Patients.

As the age increases particularly above the age of 50 years, there is a significantly higher risk of developing gallstone-related complications especially cholecystitis and common bile duct stones with its associated consequences. Complications that arise after surgical operations for cholecystitis have been reported to have negative impacts on senior patients. These effects include a higher rate of complications, a longer hospital stay, higher expenditures, and decreased patient satisfaction. Therefore, finding the most effective treatment for cholecystitis in older patients is still a challenge. The aim of the study was carried out in order to identify many approaches that can be taken in the treatment of cholecystitis and stones in the common bile duct in older patients. A search was conducted through Medline (PubMed), EMBASE, ProQuest, and Cochrane using relevant Medical Subject Heading (MeSH) terms and keywords (elderly, age over 50, cholecystitis, bile duct stones, cholecystectomy, ERCP, surgical, conservative management, and open). The searches were limited to studies on elderly individuals over 50 who had cholecystectomy and endoscopic retrograde cholangiopancreatography between January 2000 and December 2022. The meta-analysis used the Mantel-Haenszel odds ratio (MHOR) and 95% confidence interval (CI). Aries Systems Corporation's Editorial Manager® (Aries Systems Corporation, North Andover, USA) and ProduXion Manager® (Aries Systems Corporation, North Andover, USA) facilitated the study. Out of 102 citations, 39 studies were selected for further study. After that, 18 studies were eliminated, leaving 21 for meta-analysis. The study found a protective risk of cholecystitis in cholecystectomy patients (MHOR = 0.16; 95%, CI = 0.10 to 0.25; p 0.001). Developing cholecystitis was substantially lower in early cholecystectomy patients (MHOR = 0.16; 95%, CI = 0.10 to 0.25; p 0.001). There was no significant difference in cholecystitis risk between open and laparoscopic surgery (MHOR = 0.65; 95%, CI = 0.41 to 1.04; p 0.07). Cholecystectomy performed at an earlier stage protects elderly patients from developing recurrent cholecystitis. In contrast to late cholecystitis, in which the patient would experience several attacks of cholecystitis, early cholecystectomy protects against the recurrence of the condition.

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.

Virtual reality technology for surgical learning: qualitative outcomes of the first virtual reality training course for emergency and essential surgery delivered by a UK-Uganda partnership.

INTRODUCTION: The extensive resources needed to train surgeons and maintain skill levels in low-income and middle-income countries (LMICs) are limited and confined to urban settings. Surgical education of remote/rural doctors is, therefore, paramount. Virtual reality (VR) has the potential to disseminate surgical knowledge and skill development at low costs. This study presents the outcomes of the first VR-enhanced surgical training course, 'Global Virtual Reality in Medicine and Surgery', developed through UK-Ugandan collaborations. METHODS: A mixed-method approach (survey and semistructured interviews) evaluated the clinical impact and barriers of VR-enhanced training. Course content focused on essential skills relevant to Uganda (general surgery, obstetrics, trauma); delivered through: (1) hands-on cadaveric training in Brighton (scholarships for LMIC doctors) filmed in 360°; (2) virtual training in Kampala (live-stream via low-cost headsets combined with smartphones) and (3) remote virtual training (live-stream via smartphone/laptop/headset). RESULTS: High numbers of scholarship applicants (n=130); registrants (Kampala n=80; remote n=1680); and attendees (Kampala n=79; remote n=556, 25 countries), demonstrates widespread appetite for VR-enhanced surgical education. Qualitative analysis identified three key themes: clinical education and skill development limitations in East Africa; the potential of VR to address some of these via 360° visualisation enabling a 'knowing as seeing' mechanism; unresolved challenges regarding accessibility and acceptability. CONCLUSION: Outcomes from our first global VR-enhanced essential surgical training course demonstrating dissemination of surgical skills resources in an LMIC context where such opportunities are scarce. The benefits identified included environmental improvements, cross-cultural knowledge sharing, scalability and connectivity. Our process of programme design demonstrates that collaboration across high-income and LMICs is vital to provide locally relevant training. Our data add to growing evidence of extended reality technologies transforming surgery, although several barriers remain. We have successfully demonstrated that VR can be used to upscale postgraduate surgical education, affirming its potential in healthcare capacity building throughout Africa, Europe and beyond.

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.

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.

A critical appraisal of emergency resuscitative thoracotomy in a Western European level 1 trauma centre: a 13-year experience.

Emergency Resuscitative Thoracotomy (ERT) is a lifesaving procedure in selected patients. Outcome mostly in blunt trauma is believed to be poor. The primary aim of this study was to determine the predictors of postoperative mortality following ERT. We retrospectively reviewed 34 patients ≥ 18 years who underwent ERT at San Camillo-Forlanini Hospital (Rome, Italy) between January 2009 and December 2022 with traumatic arrest for blunt or penetrating injuries. Of 34 ERT, 28 (82.4%) were for blunt trauma and 6 (17.6%) were for penetrating trauma. Injury Severity Score (p-value 0.014), positive E-FAST (p-value 0.023), Systolic Blood Pressure (p-value 0.001), lactate arterial blood (p-value 0.012), pH arterial blood (p-value 0.007), and bicarbonate arterial blood (p-value < 0.001) were significantly associated with postoperative mortality in a univariate model. After adjustment, the only independent predictor of postoperative mortality was Injury Severity Score (p-value 0.048). Our experience suggests that ERT is a technique that should be utilized for patients with critical penetrating injuries and blunt trauma in patients in extremis. Our study highlights as negative prognostic factors high values of ISS and lactate arterial blood, a positive E-FAST, and low values of Systolic Blood Pressure, pH arterial blood and bicarbonate arterial blood.

A single-center, single-blinded, randomized, parallel-group, non-inferiority trial to compare the efficacy of a 22-gauge needle versus a 15 blade to perform an Achilles tendon tenotomy in 244 clubfeet-study protocol.

BACKGROUND: Achilles tendon tenotomy is an integral part of the Ponseti method, aimed at correcting residual equinus and lack of dorsiflexion after correction of the adductus deformity in clubfoot. Percutaneous tenotomy using a number 15 scalpel blade is considered the gold standard, resulting in excellent results with minimal complications. The use of a large-bore needle to perform Achilles tendon tenotomies has been described in literature, but a large-scale randomized controlled trial is currently lacking. In this trial, we aim to show the non-inferiority of the needle tenotomy technique compared to the gold standard blade tenotomy technique. METHODS: We will randomize 244 feet into group A: needle tenotomy or group B: blade tenotomy. Randomization will be done using a block randomization with random block sizes and applying a 1:1 allocation to achieve an intervention and control group of the exact same size. Children will be evaluated at 3 weeks and 3 months post-tenotomy for primary and secondary clinical outcomes. The primary clinical outcome will be the range of dorsiflexion obtained the secondary clinical outcomes will be frequency of minor and major complications and Pirani score. The non-inferiority margin was set at 4°, and thus, the null hypothesis of inferiority of the needle technique will be rejected if the mean difference between both techniques is less than 4°. The statistical analysis will use a multi-level mixed effects linear regression model for the primary outcomes and a multi-level mixed effects logistic regression model for the secondary clinical outcomes. The physician performing the evaluations post-tenotomy will be the only one blinded to group allocation. TRIAL REGISTRATION: This trial was registered prospectively with ClinicalTrials.gov registration number: NCT04897100 on 21 May 2021.

Influence of Root Canal Treatment on Oral-Health-Related Quality of Life (OHRQoL) in Saudi Patients: A Cross-Sectional Study.

Objective This cross-sectional study aimed to assess the influence of root canal treatment on the oral-health-related quality of life (OHRQoL) of patients in the Kingdom of Saudi Arabia (KSA). The data on KSA's population are significantly limited, highlighting the significance of additional research to be carried out in this particular field. Methods The study was conducted at the dental clinics of the College of Dentistry, Qassim University, from January to June 2022. A total of 112 patients who had undergone endodontic therapy (ET) for teeth with irreversible pulpitis were included. Demographic data and treatment procedures were recorded. The patients' responses to the OHIP-14 questionnaire were analyzed to assess their OHRQoL. The scores were converted into qualitative categories (good, moderate, poor) for classification. Results The majority of patients (59.8%) reported a good OHRQoL after ET. Physical pain was the only variable where more than 50% of patients reported experiencing pain. Older age and smoking status were significantly associated with a poorer OHRQoL. However, no significant gender differences in OHRQoL were observed. Conclusion ET had a positive impact on the OHRQoL of patients in Saudi Arabia. The study highlights the importance of considering patient-centered outcomes, such as OHRQoL, in assessing the success of root canal treatment. Further research with longitudinal designs and randomized controlled trials is needed to better understand the long-term effects of root canal treatment on patients' OHRQoL and to compare them with other dental treatments.

The Incidence of Hematological Toxicities in Colorectal Cancer Patients Treated With Fluoropyrimidine-Based Regimens at Princess Noorah Oncology Center.

Background Fluoropyrimidine-based regimens are used for the management of colorectal cancer, which is the second most common cancer in Saudi Arabia. We aimed to study the incidence of hematological toxicities in colorectal cancer patients treated with fluoropyrimidine and fluoropyrimidine-based regimens at Princess Noorah Oncology Center, King Abdulaziz Medical City- Jeddah, Saudi Arabia.  Methods A retrospective cohort study that included adult colorectal cancer patients who were treated with fluoropyrimidine-based regimens from January 1, 2018 to December 31, 2018 at Princess Noorah Oncology Center, Jeddah, Saudi Arabia was performed. Our primary objective was to determine the incidence of anemia, neutropenia, and thrombocytopenia in colorectal cancer patients treated with fluoropyrimidines and fluoropyrimidine-based regimens. Secondary objectives were to assess the grade of hematological toxicities associated with 5-fluorouracil (5-FU) use and to determine the frequency of unplanned hospital admissions or emergency department (ED) visits after receiving fluoropyrimidine-based regimens. The collected data contained patients' characteristics (weight, height, age, gender, and diagnosis), chemotherapy agents, and hematological toxicity-related findings such as absolute neutrophil count, hemoglobin, platelet count, and number of ED visits or hospital admissions during fluoropyrimidine-based chemotherapy regimens. Results Of the 570 cycles of the fluoropyrimidine-based regimen received by 68 patients, hematological toxicities were observed in 508 (89.1%) cycles, and grade ≥ 3 grade toxicities were found in 46 (8.1%) cycles. The results demonstrated a statistically significant difference in the incidence of grade 3-4 neutropenia between patients who received bolus administration of 5-FU and those who did not (8.5% vs. 2.3% respectively, p=0.025). The incidence of grade 3-4 anemia was higher in the bolus group (11.3%) compared to the group where bolus was omitted (4.6%); however, the difference was not statistically significant (p=0.059). Furthermore, there was no significant difference among the two groups for grade 3 and grade 4 thrombocytopenia (0.0% with bolus given and 0.7% with bolus omission p=1.00). Conclusion Our retrospective study showed that there have been significantly higher grade 3-4 hematological toxicities observed with bolus administration of 5-FU, which confirms the previous reports.

Mulliken's Bilateral Cleft Lip Repair: Early Outcome Analysis.

OBJECTIVE: To determine the early surgical outcome of Mulliken's repair technique for bilateral cleft lip. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the study: Burns and Plastic Surgery Centre, Hayatabad Medical Complex, Peshawar, Pakistan, from January 2020 to December 2021. METHODOLOGY: This study included 51 patients with bilateral cleft lip deformity. Patients were evaluated preoperatively to exclude any associated congenital anomalies or comorbidities. Then the patients were classified into mild, moderate, severe, and asymmetrical cases. Outcomes were determined immediately and one week postoperatively, as good (score 16-20), fair (score 11-15), and bad (0-10) on the basis of anthropometric measurements on outcome evaluation criteria (OEC). RESULTS: Preoperatively mild, moderate, and severe bilateral cleft lips were observed in 18 (35.3%), 6 (11.85%), and 15 (29.4%), respectively, while 10 (19.6%) were bilateral asymmetrical cleft lips. The postoperative outcome score ranged from 16 to 20 (mean 19.2+1.03) which falls in the good outcome range. Nasal symmetry was good in 64.7% (n=33) cases while 31.4% (n=16) patients had satisfactory scores. CONCLUSION: Although Mulliken's repair is by far the most prevalent type of repair for bilateral cleft lip patients, the results can vary markedly. The early outcome evaluation criteria is an objective tool to measure the outcomes. KEY WORDS: Cleft lip, Bilateral cleft lip, Mulliken, Mulliken's repair, Day care surgery, Outcome.

Percutaneous Achilles tendon tenotomy in clubfoot patients with a 22 gauge needle in a low-resource setting.

Ponseti treatment has been well-established as the gold standard for the treatment of idiopathic clubfoot in high-income countries and middle- and low-income countries (LMICs). The tenotomy is usually performed in the clinic using a scalpel blade under local anesthesia. However, we believe that by adapting the technique from Minkowitz et al. to a low-resource setting, we can help address some of the known barriers to Ponseti care. Using a needle instead of a blade makes the procedure less cumbersome easier to learn and easier to understand for the provider, family and the patient. We were able show that the needle tenotomy technique can be implemented in a low-resource setting like Pakistan, and can be performed using only one assistant and materials that are locally and readily available for the same cost This paper and its attached educational videos can help spread the technique among providers in low-resource settings.

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.

Comparison of Biosimilar Filgrastim with Innovator Fligrastim for Peripheral Blood Stem Cells Mobilization, Collection of CD34+ Stem Cells, and Engraftment in Patients Undergoing Autologous and Allogeneic Stem Cell Transplantation: A Single-Center Experience.

BACKGROUND In the Middle East, there is lack of data on peripheral blood CD34+stem cells mobilization by using biosimilar filgrastim. We have been using both Neupogen and a biosimilar G-CSF) Zarzio® (as a mobilizing agent since February 2014 for both allogenic and autologous stem cell transplantations. MATERIAL AND METHODS This was a single-center retrospective study. All patients and healthy donors who received either the biosimilar G-CSF (Zarzio®) or original G-CSF (Neupogen®) for mobilization of CD34+ stem cells were included in the study. The primary goal was to determine and compare the rate of successful harvest and amount of CD34+ stem cells collected in either adult cancer patients or healthy donors between Zarzio® and Neupogen® groups. RESULTS A total of 114 patients, including 97 cancer patients and 17 healthy donors, underwent successful CD34+ stem cell mobilization using G-CSF with chemotherapy (35 with Zarzio® +chemotherapy, 39 with Neupogen® +chemotherapy) or G-CSF as monotherapy (14 with Zarzio®, 9 with Neupogen®) in autologous transplantation. In an allogeneic stem cell transplantation, successful harvest was achieved by using G-CSF monotherapy (8 with Zarzio®, 9 with Neupogen®). There was no difference between Zarzio® and Neupogen® in the amount of CD34+ stem cells collected at leukapheresis. There was no difference with regards to secondary outcomes between the 2 groups. CONCLUSIONS Our study showed that biosimilar G-CSF (Zarzio®) has comparable efficacy to the original G-CSF (Neupogen®) when used for mobilization in both autologous and allogenic stem cell transplantation and was associated with significant cost saving.

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.

Cost-efficiency analysis of conversion to biosimilar filgrastim for supportive cancer care and resultant expanded access analysis to supportive care and early-stage HER2+ breast cancer treatment in Saudi Arabia: simulation study.

AIMS: This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient. MATERIALS AND METHODS: Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment. RESULTS: Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio). CONCLUSION: This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.

Pyrimethamine 3D printlets for pediatric toxoplasmosis: design, pharmacokinetics, and anti-toxoplasma activity.

OBJECTIVES: The focus of the present research is to develop printlet formulations of pyrimethamine (PMT). METHODS: Printlets formulation of PMT were developed by screening design by varying laser scanning speed, Kollidon® VA 64, polyvinylpyrrolidone, and disintegrant. RESULTS: Laser scanning speed, Kollidon® VA, and disintegrant had statistically significant effect on hardness, disintegration time, and/or dissolution (p < 0.05). Dissolution was almost 100% in 30 min. X-ray powder diffraction indicated partial amorphous transformation of the crystalline drug. Pharmacokinetic and anti-toxoplasma activity profiles of the printlets and compressed tablets were superimposable with no statistical difference (p > 0.05). CONCLUSION: Clinical performance of the printlets would be similar to the compressed tablets.