Safety Of Administration Research Articles

The PreQuine Platform: A novel diagnostic tool for measuring glucose-6-phosphate dehydrogenase (G6PD) activity and hemoglobin concentration.

Quantitative diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is essential for the safe administration of 8-aminoquinoline based radical cure for the treatment of Plasmodium vivax infections. Here, we present the PreQuine Platform (IVDS, USA), a quantitative biosensor that uses a dual-analyte assay for the simultaneous measurement of Hemoglobin (Hgb) levels and G6PD enzyme activity within the same sample. The platform relies on a downloadable mobile application. The device requires 10μl of whole blood and works with a reflectance-based meter. Comparing the G6PD measurement normalized by Hgb of 12 samples from the PreQuine Platform with reference measurements methods (spectrophotometry, Pointe Scientific, USA and hemoglobin meter, HemoCue, Sweden) showed a positive and significant agreement with a slope of 1.0091 and an intercept of -0.0379 under laboratory conditions. Next steps will be to conduct field trials in Bangladesh, Cambodia, and the USA to assess diagnostic performance, user friendliness and acceptance.

Assessment of Key Factors Impacting Variability in AAV Vector Genome Titration by Digital PCR

Recombinant adeno-associated virus (rAAV) has emerged as a prominent vector for in vivo gene therapy, owing to its distinct advantages. Accurate determination of the rAAV genome titer is crucial for ensuring the safe and effective administration of clinical doses. The evolution of the rAAV genome titer assay from quantitative PCR (qPCR) to digital PCR (dPCR) has enhanced accuracy and precision, yet practical challenges persist. This study systematically investigated the impact of various operational factors on genome titration in a single-factor manner, aiming to address potential sources of variability in the quantitative determination process. Our findings revealed that a pretreatment procedure without genome extraction exhibits superior precision compared with titration with genome extraction. Additionally, notable variations in titration results across different brands of dPCR instruments were documented, with relative standard deviation (RSD) reaching 23.47% for AAV5 and 11.57% for AAV8. Notably, optimal operations about DNase I digestion were identified; we thought treatment time exceeding 30 min was necessary, and there was no need for thermal inactivation after digestion. And we highlighted that thermal capsid disruption before serial dilution substantially affected AAV genome titers, causing a greater than ten-fold decrease. Conversely, this study found that additive components of dilution buffer are not significant contributors to titration variations. Furthermore, we found that repeated freeze–thaw cycles significantly compromised AAV genome titers. In conclusion, a comprehensive dPCR titration protocol, incorporating insights from these impact factors, was proposed and successfully tested across multiple serotypes of AAV. The results demonstrate acceptable variations, with the RSD consistently below 5.00% for all tested AAV samples. This study provides valuable insights to reduce variability and improve the reproducibility of AAV genome titration using dPCR.

Outpatient administration of CAR T-cell therapy: a focused review with recommendations for implementation in community based centers

Chimeric Antigen Receptor T-cell (CAR-T) therapy has transformed the treatment landscape for hematological malignancies, showing high efficacy in patients with relapsed or refractory (R/R) disease and otherwise poor prognosis in the pre-CAR-T era. These therapies have been usually administered in the inpatient setting due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). However, there is a growing interest in the transition to outpatient administration due to multiple reasons. We review available evidence regarding safety and feasibility of outpatient administration of CD19 targeted and BCMA targeted CAR T-cell therapy with an emphasis on the implementation of outpatient CAR-T programs in community-based centers.

Optimizing the Use of Dose Error Reduction Software on Intravenous Infusion Pumps.

Intravenous infusions have the potential to cause significant harm in patients and are associated with a high rate of adverse drug events and medication errors. Infusion pumps with dose error reduction software (DERS) can be used to reduce errors by establishing safe infusion parameters. In 2019, a quality improvement project was initiated with the aim to increase DERS compliance from 46% to 75% at our specialty institution by October 1, 2022. An interdisciplinary group was tasked with improving compliance with DERS by identifying key drivers, including informed staff, engaged staff, and an accurate smart pump library. We used the Model for Improvement framework to guide this improvement project, and Plan-Do-Study-Act (PDSA) cycles were used to plan for interventions. PDSA cycles included drug library updates, education, and unit-level compliance reporting. Weekly average DERS compliance was monitored as the outcome measure, and weekly pump alerts per 100 infusions were monitored as a balancing measure; statistical process control charts were used to monitor measures from 2018 to 2022. Over the course of 25 months, 8 PDSA cycles resulted in 5 centerline improvements from a baseline mean of 46% to a final mean of 78%. Pump alerts per 100 infusions decreased from 15.9 to 6.4 with the first PDSA cycle and then continued to decrease to 3.9 with subsequent interventions. Although features like DERS can help ensure safe medication administration, continuous improvement efforts to increase DERS compliance without increasing alert burden are needed to ensure that benefits of this technology are optimized.

Knowledge about Administration and Regulation of High Alert Medication among Nurses in Oncology Department

Background: High alert medications (HAMs) are associated with a higher risk of causing significant patient harm when used in error. Understanding the administration and regulation of these medications within oncology settings is critical due to the complex nature of cancer treatment regimens and the severity of potential medication errors. Objective: To assess the knowledge of nurses regarding the administration and regulation of high alert medications in an oncology department of a tertiary care hospital. Methods: A descriptive cross-sectional study was conducted among 133 registered nurses in the oncology department of Jinnah Hospital, Lahore. Data were collected using a structured questionnaire designed to evaluate nurses' knowledge of HAMs. Participants included both male (29.3%) and female (70.7%) nurses, with varying educational backgrounds and work experiences. Statistical analysis was performed using SPSS version 25, focusing on descriptive statistics such as frequencies, percentages, means, and standard deviations. Results: The results revealed moderate knowledge levels among nurses with significant gaps in critical areas. Only 20.3% correctly identified the protocol for fast IV push of 1:1000 epinephrine in mild allergic reactions, and 33.8% mistakenly believed that 10% calcium gluconate and 10% calcium chloride were interchangeable. Additionally, 44.4% incorrectly used 'Amp' or 'Vial' for dose expression instead of 'mg' or 'gm', and 53.4% failed to recognize the importance of distinctive labeling on look-alike drugs. Conclusion: The study highlights the need for enhanced educational programs and standardized protocols to improve the safe administration and regulation of HAMs in oncology settings. Strengthening nurses' knowledge and practices regarding HAMs is essential to reduce medication errors and improve patient outcomes.

Evaluation of a Novel Enteral Phosphorus Therapy with Enteral Nutrition during a National Intravenous Sodium Phosphate Shortage.

The purpose of this study was to evaluate the efficacy and safety of intragastric administration of small volumes of sodium enema solution containing phosphorus as phosphorus replacement therapy in critically ill patients with traumatic injuries who required continuous enteral nutrition. Adult patients (>17 years of age) who had a serum phosphorus concentration <3 mg/dL (0.97 mmol/L) were evaluated. Patients with a serum creatinine concentration >1.4 mg/dL (124 µmol/L) were excluded. Patients were given 20 mL of saline enema solution intragastrically, containing 34 mmol of phosphorus and mixed in 240 mL water. A total of 55% and 73% of patients who received one (n = 22) or two doses (n = 11) had an improvement in the serum phosphorus concentration, respectively. The serum phosphorus concentration increased from 2.5 [2.1, 2.8] mg/dL (0.81 [0.69, 0.90] mmol/L) to 2.9 [2.2, 3.0] mg/dL (0.94 [0.71, 0.97 mmol/L) for those who received two doses (p = 0.222). Excluding two patients with a marked decline in serum phosphorus by 1.3 mg/dL (0.32 mmol/L) resulted in an increase in the serum phosphorus concentration from 2.3 [2.0, 2.8] mg/dL (0.74 [0.65, 0.90] mmol/L) to 2.9 [2.5, 3.2] mg/dL (0.94 [0.81, 1.03] mmol/L; n = 9; p = 0.012). No significant adverse effects were noted. Our data indicated that intragastric phosphate administration using a small volume of saline enema solution improved the serum phosphorus concentrations in most patients.

Outcomes of High-Dose Versus Low-Dose Vitamin D on Prognosis of Sepsis Requiring Mechanical Ventilation: A Randomized Controlled Trial.

Background: Critically ill patients with sepsis have a high incidence of vitamin D deficiency. Vitamin D promotes the synthesis of human cathelicidin antimicrobial peptide, a precursor of LL-37, which is a part of the innate immune system. This study investigated the effectiveness and safety of the early administration of high-dose enteral vitamin D3 in comparison with low-dose vitamin D3 in patients with sepsis requiring mechanical ventilation (MV). Methods: Eighty adult patients with sepsis requiring MV with known vitamin D deficiency were randomly assigned to receive either an enteral 50 000 IU (Group I) or 5000 IU (Group II) vitamin D supplementation. Clinical and laboratory parameters were evaluated at baseline and on days 4 and 7 between the study groups. The change in serum procalcitonin (PCT) levels on day 7 was the primary outcome, while the change in serum LL-37 levels on day 7, changes in sequential organ failure assessment (SOFA) score, and clinical pulmonary infection score on day 7, MV duration, and hospital length of stay (LOS) were the secondary outcomes. Results: The (day 7-day 0) change in serum PCT and LL-37 levels and SOFA score were significantly different in Group I (P = .010, P < .001, and P < .001, respectively). The SOFA score was significantly different on days 4 and 7 in Group I (P < .001 and P < .001, respectively). The incidence of early ventilator-associated pneumonia was significantly different between both treatment groups (P = .025). The hospital LOS was shorter in Group I (P < .001). No 25-hydroxyvitamin-D toxicity was observed in either group. Conclusions: Early enteral administration of high-dose vitamin D3 in critically ill patients with sepsis requiring MV along with standard treatment for sepsis decreased serum procalcitonin levels, increased serum LL-37 levels, and ameliorated illness severity scores.

Abstract PO4-18-05: Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer

Abstract Introduction- Cannabis is world’s oldest cultivated medicinal plant. It has potential applications in oncology, in reducing chronic pain, stimulating appetite, alleviating nausea/vomiting, improving overall well-being as well as its anti-cancer properties. We conducted a phase-1 dose escalation study to determine safety of pre-operative oral cannabis in breast and oral cavity squamous cell carcinoma (OC-SCC) with an intent to explore its anticancer potential in the “pre-operative” window. The primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Methodology- Primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Non-metastatic breast and OC-SCC patients planned for curative surgery were consented after thorough medical and mini-psychiatric evaluation with Brief Psychiatry Rating Scale (BPRS). The investigational product (IP) comprised of a capsule containing 2.5mg of tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD) in 100 mg monocrotolyn oil extract of dried leaves of C. sativa. The capsules were manufactured in an Ayurvedic GMP facility. The classical 3+3, phase-1 design used modified Fibonacci sequence for dose escalation, starting with 5mg THC+5mg CBD. Patients received IP once a day for 5 days after breakfast with hemodynamic and psychiatric monitoring and underwent the planned surgery on day-6. Pharmacokinetic samples were collected at predefined time-points and plasma levels of THC, 11-OH-THC, 11-COOH-THC and CBD were determined using a validated LC-MS/MS method. Tumour tissue was collected before 1st dose of cannabis and during surgery for biomarker analysis. Results- A total of 12 patients were enrolled (6-breast, 3-buccal mucosa, and 3-tongue cancers). First 3 patients completed the study without DLT at 5+5mg dose. A DLT was observed at dose level-2 (10+10mg) and therefore additional 3 patients were enrolled at the same dose. Two patients out of six at this dose had DLT (anxiety- grade-3 and somnolence- grade-2) necessitating dose de-escalation in the next cohort. At 7.5+7.5mg dose, all 3 patients tolerated the IP(MTD). Ten patients completed the study protocol. Common adverse effects were headache (2/12, grade-1), heavy head (8/12, grade-1), hypotension (2/12, grade-1 and 3), epigastric discomfort (1/12, grade-1), diarrhoea (1/12, grade-1), hyponatremia (1/12, grade-1), hypertension (1/12, grade-2), anxiety (1/12, grade-2). Pharmacokinetics of both CBD and THC was less than dose proportional. At the MTD (7.5+7.5), day-1 and day-5 AUC0-24 [median (range)] for CBD were 21.75 (12.44–41.44) ng/ml−1*h and 24.85 (13.72–35.93) ng/ml−1*h respectively. Similarly, for THC, day 1 and day 5 AUC0-24 were 11.79 (8.06–70.58) ng/ml−1*h and 68.98 (1.78 – 136.17) ng/ml−1*h, respectively. Significant accumulation of both CBD and THC was observed across all doses from day 1 to 5. A high variability in pharmacokinetics was observed for both constituents (CV Cmax = 101.26% and 117.48%; CV AUC0-24 = 102.50% and 112.37% for CBD and THC respectively. The median half-life of CBD and THC was 2.2 (1.6–10.7) and 1.9 (1.6–2.4) h respectively. There was no correlation observed between drug exposure and toxicity. There was no significant change in BPRS score before and after IP. Conclusion- We report the first phase-1 study of cannabis in breast and OC-SCC cancer in pre-operative setting for its anti-cancer potential. Biomarker analysis is awaited. MTD identified will be further explored in phase 2/3 clinical trials in breast, oral cavity, lung and pancreatic cancer with survival endpoints. Citation Format: Rajendra Badwe, Shalaka Joshi, Shiva Thiagarajan, Vikram Gota, Vaibhav Vanmali, Pallavi Daphale, Jayita Deodhar, Rohan Chaubal, Rohini Hawaldar, Jaya Chitra Aadhi, Saurabh Kumar Gupta, Delzaad Deolaliwala, Anil Bhansali, Siddhant Mistry, Satyajeet Singh, Nita Nair, Vani Parmar, Sudeep Gupta. Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-05.

Direct 3D printing of triple-responsive nanocomposite hydrogel microneedles for controllable drug delivery

Hydrogel microneedle patches have emerged as promising platforms for painless, minimally invasive, safe, and portable transdermal drug administration. However, the conventional mold-based fabrication processes and inherent single-functionality of such microneedles present significant hurdles to broader implementation. Herein, we have developed a novel approach utilizing a precursor solution of robust nanocomposite hydrogels to formulate photo-printable inks suitable for the direct 3D printing of high-precision, triple-responsive hydrogel microneedle patches through digital light processing (DLP) technology. The ink formulation comprises four functionally diverse monomers including 2-(dimethylamino)ethyl methacrylate, N-isopropylacrylamide, acrylic acid, and acrylamide, which were crosslinked by aluminum hydroxide nanoparticles (AH NPs) acting as both reinforcing agents and crosslinking centers. This results in the formation of a nanocomposite hydrogel characterized by exceptional mechanical strength, an essential attribute for the 3D printing of hydrogel microneeedle patches. Furthermore, this innovative 3D printing strategy facilitates facile customization of microneedle geometry and patch dimensions. As a proof-of-concept, we employed the fabricated hydrogel microneedles for transdermal delivery of bovine serum albumin (BSA). Importantly, these hydrogel microneedles displayed no cytotoxic effects and exhibited triple sensitivity to pH, temperature and glucose levels, thereby enabling more precise on-demand drug delivery. This study provides a universal method for the rapid fabrication of hydrogel microneedles with smart responsiveness for transdermal drug delivery applications.

Risk of Enzyme- and Transporter-Mediated Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2022: A Detailed Analysis of In Vitro and Clinical Data Available in New Drug Application Reviews

PurposeThis analysis aimed to provide mechanistic understanding and clinical relevance of pharmacokinetic drug-drug interactions (DDIs) associated with drugs approved by the Food and Drug Administration in 2022. MethodsDrug metabolism, transport, and DDI data available in New Drug Applications (NDAs) of small molecular drugs approved (n = 22) was analyzed. The mechanism and clinical magnitude of these interactions were characterized based on in vitro, in silico, and clinical data. FindingsAs victims, 10 drugs were identified as clinical substrates. Of these, 7 drugs were substrates of CYP3A, including the sensitive substrates daridorexant and mitapivat. As perpetrators, 3 drugs (adagrasib, lenacapavir, and vonoprazan) were clinical inhibitors of CYP enzymes, and 2 drugs (mavacamten and mitapivat) showed induction. Regarding transporter data, abrocitinib and deucravacitinib were found to be substrates of OAT3 and P-gp/BCRP, respectively, and 4 drugs (abrocitinib, adagrasib, lenacapavir, and oteseconazole) were found to inhibit P-gp and/or BCRP. As expected, all clinical DDIs with AUC changes ≥ 2-fold triggered label recommendations. Over half of DDIs with an AUC change < 2 also had label recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Overall, CYP3A played a major role in the drug disposition of the drugs approved in 2022, mediating all strong drug interactions. ImplicationsThe mechanistic information obtained from studying these new therapeutics with marker compounds can be extrapolated to common concomitant medications sharing the same pharmacokinetic properties, enhancing the safe and effective administration of these products in situations of polytherapy.

The impact of healthcare information technology on reducing medication errors: A review of recent advances

This review explores the impact of HIT on reducing medication errors, encompassing recent advances in electronic health records (EHRs), clinical decision support systems (CDSS), bar-coding technology, telemedicine, and mobile health applications. By synthesizing evidence from scholarly literature, case studies, and real-world implementations, this paper delineates the multifaceted benefits, challenges, and future prospects of integrating HIT into medication management processes. Understanding the evolving role of HIT in error reduction is pivotal for healthcare stakeholders to optimize patient outcomes and enhance the quality and safety of medication administration. In the dynamic realm of modern healthcare, medication errors loom as a formidable challenge, imperiling patient safety, compromising care quality, and inflating healthcare expenditures. However, amidst this backdrop of concern, healthcare information technology (HIT) emerges as a beacon of hope, offering potent remedies to counteract these errors. This review embarks on a journey to unravel the profound impact of HIT on ameliorating medication errors, delving into recent strides across various fronts including electronic health records (EHRs), clinical decision support systems (CDSS), bar-coding technology, telemedicine, and mobile health applications. Drawing upon a rich tapestry of scholarly literature, real-world case studies, and practical implementations, this paper meticulously examines the multifaceted landscape of HIT's influence on medication management. Through a comprehensive synthesis of evidence, we uncover the diverse benefits, confront the inherent challenges, and illuminate the promising vistas that emerge from the integration of HIT into medication-related processes. At the core of this exploration lies an urgent call to comprehend the evolving role of HIT in error reduction, recognizing its pivotal significance for healthcare stakeholders. By assimilating insights from disparate sources, we endeavor to empower stakeholders with the knowledge necessary to optimize patient outcomes, fortify the fabric of care delivery, and foster a culture of safety and excellence in medication administration. In essence, this review serves as a guiding compass amidst the labyrinth of healthcare challenges, illuminating pathways towards safer, more efficient, and more effective medication management practices. As we navigate this terrain, let us remain steadfast in our commitment to harness the transformative power of HIT, thereby ushering in a new era of enhanced patient safety, elevated care quality, and sustainable healthcare systems. In the contemporary healthcare landscape, medication errors represent a significant concern, posing risks to patient safety, quality of care, and overall healthcare costs. However, advancements in healthcare information technology (HIT) offer promising solutions to mitigate these errors.

HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation.

Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective anti-leukemic effect post-HCT. We conducted a phase I clinical trial employing a novel TCR-T product targeting the minor H antigen HA-1 to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms. The primary objective was to evaluate the feasibility and safety of administration of HA-1 TCR-T post-HCT. CD8+ and CD4+ T cells expressing the HA-1 TCR and a CD8-co-receptor were successfully manufactured from HA-1 disparate HCT donors. One or more infusions of HA-1 TCR-T following lymphodepleting chemotherapy were administered to nine HCT recipients who had developed disease recurrence post-HCT. TCR-T cells expanded and persisted in vivo after adoptive transfer. No dose-limiting toxicities occurred. Although the study was not designed to assess efficacy, four patients achieved or maintained complete remissions following lymphodepletion and HA-1 TCR-T, with one ongoing at >2 years. Single-cell RNA sequencing of relapsing/progressive leukemia after TCR-T therapy identified upregulated molecules associated with T cell dysfunction or cancer cell survival. HA-1 TCR-T therapy appears feasible and safe and shows preliminary signals of efficacy. This clinical trial is registered at clinicaltrials.gov as NCT03326921.

Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear. We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

Fabrication and characterisation of nabumetone transferosomal gel for effective topical delivery

Nabumetone is a lipophilic drug with a log P value of 3.2 and belongs to BCS class II due to its poor water solubility. When administered orally, it undergoes extensive first-pass metabolism, shows low bioavailability, and has unfavourable side effects that cause discomfort. Topical route has gain importance by delivering therapeutic agents via this route due to its safety and convenience of drug administration and as of there are no any gel formulations available for it. The present investigation aimed to prepare, optimise, and characterise Nabumetone-loaded transferosomes (Nb-TF) using 32 factorial designs. Transferosomes were prepared by the thin-film hydration method. The optimised formulation was incorporated into gel form (Nb-TG) and evaluated for its mechanical characteristics, in-vitro release, ex-vivo permeation, skin irritancy test, anti-inflammatory activity, and stability studies. The Nb-TF 5 transferosomal formulation was optimised based on vesicle size and entrapment efficiency and incorporated into the gel base. Both normal (Nb-gel) and transferosome-loaded (Nb-TG) gel pH was within the range of topical skin pH. The viscosities of Nb-gel and Nb-TG were 1262 ± 54 cP and 1327 ± 12 cP, respectively. The drug content of both gels was found to be 96.31 ± 1.16 and 97.18 ± 0.94, respectively. Nb-TG showed higher diffusion and drug permeation than Nb-gel. The skin irritancy test indicates that there was no sign of any edema or erythema observed. Nb-TG showed a curative and preventive anti-inflammatory effect. Gels were found stable at both refrigerator and room temperature. Nb-TFs were proven to be potential carriers for transdermal controlled delivery of Nabumetone as it has deep penetration in the dermis layer which directly goes into the systemic circulation, enhances the bioavailability and reduced toxicities.

Point Prevalence Survey of Acute Hospital Patients with Difficulty Swallowing Solid Oral Dose Forms

The safe administration of solid oral dose forms in hospital inpatients with swallowing difficulties is challenging. The aim of this study was to establish the prevalence of difficulties in swallowing solid oral dose forms in acute hospital inpatients. A point prevalence study was completed at three time points. The following data were collected: the prevalence of swallowing difficulties, methods used to modify solid oral dose forms to facilitate administration, the appropriateness of the modification, and patient co-morbidities. The prevalence of acute hospital inpatients with swallowing difficulties was an average of 15.4% with a 95% CI [13.4, 17.6] across the three studies. On average, 9.6% of patients with swallowing difficulties had no enteral feeding tube in situ, with 6.0% of these patients receiving at least one modified medicine. The most common method of solid oral dose form modification was crushing, with an administration error rate of approximately 14.4%. The most common co-morbid condition in these patients was hypertension, with dysphagia appearing on the problem list of two (5.5%) acute hospital inpatients with swallowing difficulties. Inappropriate modifications to solid oral dose forms to facilitate administration can result in patient harm. A proactive approach, such as the use of a screening tool to identify acute hospital inpatients with swallowing difficulties, is required, to mitigate the risk of inappropriate modifications to medicines to overcome swallowing difficulties.

Interventional diagnosis and treatment methods of discogenic and musculoskeletal low back pain

Low back pain (lumbar pain) is one of the most common causes of disability in the population. In cases where conservative treatment of discogenic or musculoskeletal low back pain does not have a positive effect, interventional methods of diagnosis and treatment are used, which are developing actively on the background of rapid technological progress. Being on the border of interdisciplinary interaction, interventional methods can significantly shorten the duration of conservative therapy and, in many cases, avoid surgical decompressive interventions, which are associated with a considerable risk of complications. The methods, efficacy and safety of epidural administration of glucocorticoids for discogenic radiculopathy and lumbar stenosis as well as the methods of radiofrequency denervation for musculoskeletal pain due to the facet joints and the sacroiliac joint involvement are discussed. The possibilities of drug therapy for musculoskeletal pain of the lumbar spine, and combination of non-steroidal anti-inflammatory drugs and a vitamin B complex, are discussed.

Application and evaluation of topical amphotericin B for the treatment of respiratory fungal infections

BackgroundIn recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections.MethodsWe conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023.ResultsData from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects.ConclusionThe combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

E077 Evaluation of group education for patients with large vessel vasculitis prescribed subcutaneous methotrexate

Abstract Background/Aims Patient education in rheumatology is of proven value to educate as well as to reduce demand on health care services. This can be delivered in a multitude of ways, in person and more recently with the use of multi-media modalities. There is limited evidence to specifically demonstrate the benefit of patient education for patients with vasculitis. Education needs to be adapted to meet patient needs. In addition to one-to-one appointments, we have been conducting in-person group education for this patient group. We present our experience. Methods Patients prescribed subcutaneous methotrexate for large vessel vasculitis were given the opportunity to attend a group education session run by the specialist nurse. The sessions were held over a 4-month period, in groups of 3-5 individuals. Patients were provided with written information including the links to online resources prior to attending the group education session which consisted of a verbal presentation and a short video. Patients also had the opportunity to ask questions during the group session. If patients were happy to proceed with the planned treatment, a prescription for the subcutaneous methotrexate was provided and initial blood monitoring commenced. After attending the group session, patients were given an evaluation form to complete Results The responses from the evaluation forms are shown in the following table: Conclusion Group education has proved to be a successful way of providing education to patients with large vessel vasculitis needing to learn about the indications for use, along with the safe handling and administration of subcutaneous methotrexate. Disclosure G. Ducker: None. C.B. Mukhtyar: None.

Time Savings and Safety of EMS Administration of Antibiotics for Open Fractures

ABSTRACT Introduction Early administration of antibiotics for open fractures reduces serious bone and soft tissue infections. The effectiveness of antibiotics in reducing these infections is time-dependent, with various surgical associations recommending administration within one hour of injury, or within one hour of patient arrival to the emergency department (ED). The extent to which prehospital antibiotic administration in these situations might reduce the time to treatment has not been previously reported. The purpose of this study was to describe current prehospital use of antibiotics for traumatic injury, to assess the safety of prehospital antibiotic administration, and to estimate the potential time-savings associated with antibiotic administration by EMS clinicians. Methods This was a retrospective analysis of the 2019 through 2022 ESO Data Collaborative research data set. Included subjects were patients that had a linked ICD-10 code indicating an open extremity fracture and who received prehospital antibiotics. Time to antibiotic administration was calculated as the elapsed time from EMS dispatch until antibiotic administration. The minimum potential time saved by EMS antibiotic administration was calculated as the elapsed time from administration until ED arrival. To assess safety, epinephrine and diphenhydramine administration were used as proxies for the adverse events of anaphylaxis and minor allergic reactions. Results There were 523 patients meeting the inclusion criteria. The median (and interquartile range [IQR]) elapsed time from EMS dispatch until antibiotic administration was 31 (IQR: 24-41) minutes. The median potential time savings associated with prehospital antibiotic administration was 15 (IQR: 8-22) minutes. Notably, 144 (27.5%) of the patients who received prehospital antibiotics had total prehospital times exceeding one hour. None of the patients who received antibiotics also received epinephrine for presumed anaphylaxis. Conclusions EMS clinicians were able to safely administer antibiotics to patients with open fractures a median of 15 minutes before arrival at the hospital, and 99 percent of the patients receiving antibiotics had them administered within one hour of EMS dispatch. EMS administration of antibiotics may be a safe way to increase compliance with recommendations for early antibiotic administration for open fractures.

Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.