Drug Administration Research Articles

Evaluating the efficacy of simulation-based training on clinical competency transfer

Introduction. Efficient learning transfer is crucial for training specialists to ensure the provision of quality medical services. This study investigates the impact of simulation-based training on the transfer of medical students' clinical competencies in parenteral drug administration: subcutaneous (SC), intramuscular (IM), and intravenous (IV). Material and methods. Using a quasi-experimental design, the research incorporates pre- and post-intervention testing, observational assessments, and a satisfaction survey to evaluate the educational impact. Results. The results indicate significant improvements in theoretical knowledge and practical skills post-intervention, with notable score increases for all types of injections (SC: from 50% to 83.33%, IM: from 57.14% to 85.71%, IV: from 42.86% to 85.71%; p<0.001). Similarly, improved clinical performance was demonstrated, highlighting the transferability of the learned competencies to real settings. Student satisfaction recorded a score of 4.71 (95% CI 4.64; 4.79), reflecting strong acceptance and appreciation of the training. Conclusions. The study emphasizes the crucial role of simulation in competency-based medical education, bridging the gap between theoretical knowledge and practical application, and advocates for the systematic integration of simulation into the medical curriculum, suggesting future research directions for optimizing the design and implementation of simulations.

Pharmacological management of pediatric insomnia

Insomnia is the most commonly reported sleep disorder among children and adolescents, impacting their cognitive, emotional, behavioral, and physical development. The prevalence of insomnia generally increases with age, often persisting into adulthood if unaddressed. Insomnia is exceedingly common among those with developmental disabilities and is frequently comorbid with a great range of psychiatric diagnoses. The COVID-19 pandemic has only increased the prevalence of insomnia among children and adolescents. Health care providers are routinely called upon to treat insomnia in the pediatric population. Psychoeducation and behavioral interventions, especially cognitive behavioral therapy for insomnia (CBT-I), remain the first line treatments, given empirical evidence for their efficacy and success in relapse prevention. However, medications are frequently employed in clinical practice, despite the fact that no medications are approved by the Food and Drug Administration (FDA) for the treatment of pediatric insomnia. This review was designed to educate and support practitioners who are treating children and adolescents who struggle with insomnia. A thorough narrative review was completed to identify all published medication studies of pediatric insomnia; the identified studies are described and then graded into four categories according to the strength of the evidence supporting their use, side effect profiles, co-morbidities, and overall risk vs. benefit of each pharmacological treatment. This review will help practitioners in making clinical decisions for their pediatric patients who suffer with insomnia.

Medication errors involving intravenous paracetamol in children: experience from enquiries to the National Poisons Information Service

IntroductionChildren are at higher risk of medication errors due to the complexity of drug prescribing and administration in this patient group. Intravenous (IV) paracetamol overdose differs from overdose by ingestion...

Ethnobotanical Studies of Reputed Aphrodisiac Plants Used in Traditional Medicine in Haut-Katanga in DR of Congo

The goal of this study is to identify the plants used to treat sexual dysfunction in Haut-Katanga (DRC). Since most couples in sexual distress believe that resolving sexual dysfunction (SD) is the key to happiness, an ethnobotanical survey using a questionnaire guide was conducted among 36 traditional practitioners in four sites in Haut-Katanga province, including Lubumbashi, the provincial capital. The survey identified 52 species of aphrodisiac plants that are used to treat SD. Of these, 51 have been scientifically identified; they belong to 45 different genera and are contained in 28 families, with the Fabaceae having the highest representation (15.7%). These species are employed singly or in combination to prepare eighty recipes; the most common plant organ was the root bark (63%) in these recipes. Aqueous decoction (44%) and oral administration (75.3%) are the most commonly used routes of drug preparation and administration. Nearly 80 additional indications for the same plant species were discovered to be employed, such as sexually transmitted infections (7.17%), diabetes (3.69%), and hemorrhoids (4.07%). For every species, the Informant Consensus Factor (ICF) was determined. The plants with higher values (ICF≥0.17) included Bersama abyssinica Fres, Garcinia huillensis Welw, Cassia petersiana Bolle, Chenopodium album L, Clerodendrum capitatum (Willd) Schumach, Dialiopsis africana Radlk., Albizia adianthifolia (Schum.) W. Wight, and Crossopteryx febrifuga Mull.Arg.

Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension.

Sildenafil, approved for pulmonary arterial hypertension (PAH), has a recommended adult dose of 20 mg TID, with a previously approved 5-mg TID dose by the US Food and Drug Administration. Safety concerns arose because of common off-label use of higher doses, particularly after pediatric data linked higher doses to increased mortality. To assess this, the Food and Drug Administration mandated a study evaluating the effects of various sildenafil doses on mortality in adults with PAH. This randomized, double-blind study compared sildenafil at doses of 5, 20, or 80 mg TID in adults with PAH. The primary objective was noninferiority of 80 mg of sildenafil versus 5 mg for all-cause mortality. Secondary end points included time to clinical worsening and change in 6-minute walk distance at 6 months. Interim analyses were planned at 50% and 75% of the anticipated mortality events. Safety and tolerability were assessed in the intention-to-treat population. The study was halted after the first interim analysis, demonstrating noninferiority for 80 mg of sildenafil versus 5 mg. Of 385 patients enrolled across all dose groups, 78 died. The primary analysis showed a hazard ratio of 0.51 (99.7% CI, 0.22-1.21; P<0.001 for noninferiority) for overall survival comparing 80 mg of sildenafil with 5 mg. Time to clinical worsening favored 80 mg of sildenafil compared with 5 mg (hazard ratio, 0.44 [99.7% CI, 0.22-0.89]; P<0.001). Sildenafil at 80 mg improved 6-minute walk distance from baseline at 6 months compared with 5 mg (least square mean change, 18.9 m [95% CI, 2.99-34.86]; P=0.0201). No significant differences were found between 80 mg of sildenafil and 20 mg in mortality, clinical worsening, and 6-minute walk distance. Adverse event-related drug discontinuations were numerically higher with 80 mg of sildenafil. Sildenafil at 80 mg was noninferior to sildenafil at 5 mg when examining all-cause mortality in adults with PAH. Secondary efficacy end points favored 80 mg of sildenafil over 5 mg. On the basis of these findings, the Food and Drug Administration recently revoked the approval of 5 mg of sildenafil for adults with PAH, reinforced 20 mg TID as the recommended dose, and now allows dose titration up to 80 mg TID, if needed. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060487.

Real-Life Evidence of Mepolizumab Treatment in Chronic Rhinosinusitis with Nasal Polyps: A Multicentric Study

Background: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. Methods: A retrospective data analysis was jointly conducted at the Otolaryngology–Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow–up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. Results: Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. Conclusions: Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients’ response to biological treatment in CRSwNP.

Alterations in pharmacogenetic genes and their implications for imatinib resistance in Chronic Myeloid Leukemia patients from an admixed population.

Imatinib is the tyrosine kinase inhibitor used as the gold standard for the treatment of Chronic Myeloid Leukemia. However, about 30% of patients do not respond well to this therapy. Variants in drug administration, distribution, metabolism and excretion (ADME) genes play an important role in drug resistance especially in admixed populations. We investigated 129 patients diagnosed with Chronic Myeloid Leukemia treated with imatinib as first choice therapy. The participants of the study are highly admixed, populations that exhibit genetic diversity and complexity due to the contributions of multiple ancestral groups. Thus, the aim of this work was to investigate the association of 30 SNVs in genes related to response to treatment with Imatinibe in CML. Our results indicated that for the rs2290573 of the ULK3 gene, patients with the recessive AA genotype are three times more likely to develop resistance over time (secondary resistance) (p = 0.019, OR = 3.19, IC 95%= 1.21-8.36). Finally, we performed interaction analysis between the investigated variants and found several associations between SNVs and secondary resistance. We concluded that the variant rs2290573 of the ULK3 gene may be relevant for predicting treatment response of CML with imatinib, as well as possible treatment resistance. The use of predictive biomarkers is an important tool for therapeutic choice of patients, improving their quality of life and treatment efficacy.

Recent advancements in lipid nanoparticle technology for oral insulin delivery

Nanotechnology is important in many industries, particularly in drug delivery and administration. This technology has been used to create nanocarriers for enteral drug delivery. There are different types of nanocarriers including polysaccharide-based and lipid-based nanocarriers. Lipid nanoparticles have recently been developed for loading and administering insulin via the enteral route to treat diabetes mellitus. Insulin cannot be administered orally due to its low bioavailability, extreme gastrointestinal conditions, and instability. When insulin is loaded onto these nanocarriers, it increases bioavailability, stability, drug release pattern control, and protects insulin from extreme conditions. This review article aims to discuss recent applications as well as novel methods and approaches for oral insulin delivery using liposomes, solid lipid nanoparticles, and nanostructured lipid carriers.

Factors influencing serum concentrations of levetiracetam in dogs with epilepsy.

Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy. Higher PO doses of levetiracetam will be needed in dogs to achieve serum concentrations shown to be effective in humans. Determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in some epileptic dogs. Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam. Retrospective cohort study. Linear mixed models were used to assess the effect of patient signalment and concurrent drug administration on serum concentrations of levetiracetam and the effect of serum concentration of levetiracetam on seizure frequency reduction. The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R2 = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R2 = 0.30, P = .003). Based on our model, a levetiracetam dosage of 99-216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified. Our data suggest that a dosage of 99-216 mg/kg/day of levetiracetam is needed to achieve a serum concentration known to be therapeutically effective in humans, especially when administered concomitantly with phenobarbital.

Comparison of the effectiveness of temporomandibular joint osteoarthritis treatment with corticosteroids, hyaluronic acid, and platelet-rich plasma mono-therapy

The prevalence of temporomandibular joint (TMJ) osteoarthritis is 18–85 % of all TMJ dysfunctional conditions. Most patients are elderly, especially women. Today, intra-articular injections are often used for treatment, so it is necessary to study the effectiveness of drug administration on the course of the disease. The number of studies on the effectiveness of certain drugs most commonly used to treat TMJ osteoarthritis is limited, that does not allow correct treatment planning in each individual case. Aim: to evaluate the effectiveness of TMJ osteoarthritis treatment with monotherapy with hyaluronic acid, corticosteroids, and platelet-rich plasma. Materials and methods. We included 90 patients who received intra-articular injections. Patients were randomly divided into 3 groups: group I, which received platelet-rich plasma (PRP, n = 30), group II, which received hyaluronic acid (HA, n = 30), group III, which received corticosteroids (CS, n = 30). To objectively evaluate the effectiveness of TMJ osteoarthritis treatment with monotherapy of hyaluronic acid, corticosteroids and platelet-rich plasma, the following indicators were used: filling in the visual analogue pain scale, maximum mouth opening (mm) and cortical plate density of the articular head of the mandible according to the Hounsfield scale using CBCT. Results. PRP therapy demonstrated the highest efficacy in the form of monotherapy for all study parameters (p &lt; 0.05). The fastest pain reduction was achieved with the use of corticosteroids (p &lt; 0.05). In general, during the treatment period, the reduction of pain according to the visual analogue scale in group I was 85.71 %. In patients of group II (HA) and group III (CS) – by 71.42 %. Maximum mouth opening after treatment in group I increased by 24.32 %, in group II – by 15.79 %, in group III – by 18.92 %. The density of the articular head according to the Hounsfield scale after treatment in group I increased by 12.56 %, in group II – by 6.97 %, in group III – by 4.87 %. Conclusions. All of the studied drugs demonstrated a positive effect on the treatment of TMJ osteoarthritis, but monotherapy with intra-articular PRP injections demonstrated the highest effectiveness according to the studied parameters (p &lt; 0.05).

NFS-07. RESPONSE OF A CENTRAL NERVOUS SYSTEM (CNS) HEMANGIOBLASTOMA TO BELZUTIFAN IN A PEDIATRIC PATIENT WITH VON HIPPEL-LINDAU DISEASE (VHL)

Abstract BACKGROUND VHL is a rare cancer predisposition syndrome which affects many organ systems, leading to renal clear cell carcinoma (RCC), pheochromocytoma, retinal angiomas and CNS hemangioblastomas. Surgical resection has traditionally been the mainstay of treatment of VHL-associated tumors. In 2021, belzutifan, a Hypoxia Inducible Factor 2-alpha inhibitor was approved by the Food and Drug Administration for the treatment of VHL-associated RCC based on efficacy in adults. There is a paucity of data in pediatric VHL patients with hemangioblastoma treated with this novel agent. Herein we present such a case. CASE A 15-year-old male, diagnosed with VHL caused by a de novo germline mutation at the age of 12, was found to have a left craniocervical junction lesion consistent with a hemangioblastoma on surveillance MRI. The lesion demonstrated growth upon serial imaging but remained asymptomatic. Due to location, the patient was started on medical treatment using once daily oral belzutifan (120mg) continuously, sperm banking was performed prior to initiation of therapy. Hematologic and metabolic laboratory values were monitored, in addition to regular physical examinations including blood oxygen saturation recordings. The first MRI on therapy (3 months after treatment started) demonstrated a major radiologic response using RANO criteria. Treatment has been overall very well tolerated with few treatment-related toxicities limited to CTCAE v5 grade 1 fatigue and grade 2 anemia. No dose reductions or interruptions were required. The patient remains on therapy and has completed 11 months of treatment with further reduction in the size of this target lesion. CONCLUSION Hemangioblastomas are preponderantly characterized by their highly vascular nature making surgical resection in some cases arduous depending on location. This unique pediatric case adds to the growing evidence that therapy with belzutifan may be a safe and efficacious option for VHL-associated CNS Hemangioblastomas. Prospective studies in children are needed.

Comparison of the effectiveness of temporomandibular joint osteoarthritis treatment with corticosteroids, hyaluronic acid, and platelet-rich plasma mono-therapy

The prevalence of temporomandibular joint (TMJ) osteoarthritis is 18–85 % of all TMJ dysfunctional conditions. Most patients are elderly, especially women. Today, intra-articular injections are often used for treatment, so it is necessary to study the effectiveness of drug administration on the course of the disease. The number of studies on the effectiveness of certain drugs most commonly used to treat TMJ osteoarthritis is limited, that does not allow correct treatment planning in each individual case. Aim: to evaluate the effectiveness of TMJ osteoarthritis treatment with monotherapy with hyaluronic acid, corticosteroids, and platelet-rich plasma. Materials and methods. We included 90 patients who received intra-articular injections. Patients were randomly divided into 3 groups: group I, which received platelet-rich plasma (PRP, n = 30), group II, which received hyaluronic acid (HA, n = 30), group III, which received corticosteroids (CS, n = 30). To objectively evaluate the effectiveness of TMJ osteoarthritis treatment with monotherapy of hyaluronic acid, corticosteroids and platelet-rich plasma, the following indicators were used: filling in the visual analogue pain scale, maximum mouth opening (mm) and cortical plate density of the articular head of the mandible according to the Hounsfield scale using CBCT. Results. PRP therapy demonstrated the highest efficacy in the form of monotherapy for all study parameters (p &lt; 0.05). The fastest pain reduction was achieved with the use of corticosteroids (p &lt; 0.05). In general, during the treatment period, the reduction of pain according to the visual analogue scale in group I was 85.71 %. In patients of group II (HA) and group III (CS) – by 71.42 %. Maximum mouth opening after treatment in group I increased by 24.32 %, in group II – by 15.79 %, in group III – by 18.92 %. The density of the articular head according to the Hounsfield scale after treatment in group I increased by 12.56 %, in group II – by 6.97 %, in group III – by 4.87 %. Conclusions. All of the studied drugs demonstrated a positive effect on the treatment of TMJ osteoarthritis, but monotherapy with intra-articular PRP injections demonstrated the highest effectiveness according to the studied parameters (p &lt; 0.05).

Phloroglucinol ameliorated methylglyoxal induced harmful effects in rats.

Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug.

A Comprehensive Review on Niosomes in Drug Delivery and Recent Advancements

The recent emphasis on nanocarrier development for drug delivery stems from the need to target specific diseased areas while sparing healthy tissues. Effective and safe drug administration has long posed challenges in medicine. Over the past decade, the emergence of vesicles as a means to enhance drug delivery has captivated researchers in the field of drug delivery systems. Among vesicular systems, niosomes have gained attention due to their nonionic features. Unlike liposomes, niosomes offer superior stability, making them a preferred choice. Non-ionic in nature niosomes offer unique advantages in drug delivery providing a versatile platform for encapsulating various drugs to enhance bioavailability and ensure controlled release. Understanding preparation techniques enables tailored applications from oral to transdermal delivery. Characterization methods such as morphology and particles size are pivotal in ensuring the stability and effectiveness of niosomes. Applications span cancer therapy, diagnostic imaging, and vaccination adjuvants, showcasing niosomes versatility. Ongoing research reflects dynamic efforts to enhance capabilities, emphasizing their pivotal role in evolving drug delivery systems. In this comprehensive review, we aim to encapsulate fundamental aspects of niosomes, encompassing diverse preparation methods, various niosomal types, methods for characterization and the advancements witnessed in niosomal research over the past decade, drawing insights from a literature review. Keywords: Niosomes, Drug delivery, Nanocarrier, Vesicles, Nanomedicines

Pharmacovigilance of esketamine nasal spray: an analysis of the FDA adverse event reporting system database

Pharmacovigilance of esketamine nasal spray: an analysis of the FDA adverse event reporting system database

ТЕРАПЕВТИЧЕСКИЙ ЛЕКАРСТВЕННЫЙ МОНИТОРИНГ БЕДАКВИЛИНА ПРИ ЛЕЧЕНИИ ДЕТЕЙ С ТУБЕРКУЛЕЗОМ ОРГАНОВ ДЫХАНИЯ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ

Use of Bedaquiline in children is studied relatively rarely therefore, according to the WHO experts, it is necessary to further conduct the research on the effectiveness and safety of including of the Bedaquiline drug in chemotherapy regimens in children as well as to obtain the new data on the characteristics of its metabolism in routine clinical practice. The purpose of this research was to evaluate the therapeutic monitoring performance of the Bedaquiline drug use in treatment of pediatric patients with multidrug-resistant tuberculosis (TB). Materials and methods used: pharmacokinetic (PK) parameters were determined in 10 patients of both genders aged 6 to 17 y/o who had received Bedaquiline drug as part of complex therapy in the treatment regimen for multidrug-resistant TB (MDR-TB). All patients had not received anti-tuberculosis drugs previously. Results: during the period of initial daily administration (saturation) of the Bedaquiline drug, Cmax was 3901 ng/ml, Cmin 165 ng/ml, Me 1672 (781.7-2562.3; 95% CI) ng/ml. During the period of maintenance dose intake (3 times per week) prior to taking the drug, Cmax was 987 ng/ml, Cmin 251 ng/ml, Me 504 (340.2-667.7; 95% CI) ng/ml, two hours after Bedaquiline intake Cmax was 2387 ng/ml, Cmin 576 ng/ml, Me 1429 (1005.9-1852.1; 95% CI) ng/ml. Conclusion: the data obtained coincide with the bibliographical data on the Bedaquiline PK in children aged 5 to 8 y/o issues.

Bridging the Clinical-Computational Transparency Gap in Digital Pathology.

Computational pathology combines clinical pathology with computational analysis, aiming to enhance diagnostic capabilities and improve clinical productivity. However, communication barriers between pathologists and developers often hinder the full realization of this potential. To propose a standardized framework that improves mutual understanding of clinical objectives and computational methodologies. The goal is to enhance the development and application of computer-aided diagnostic (CAD) tools. The article suggests pivotal roles for pathologists and computer scientists in the CAD development process. It calls for increased understanding of computational terminologies, processes, and limitations among pathologists. Similarly, it argues that computer scientists should better comprehend the true use cases of the developed algorithms to avoid clinically meaningless metrics. CAD tools improve pathology practice significantly. Some tools have even received US Food and Drug Administration approval. However, improved understanding of machine learning models among pathologists is essential to prevent misuse and misinterpretation. There is also a need for a more accurate representation of the algorithms' performance compared to that of pathologists. A comprehensive understanding of computational and clinical paradigms is crucial for overcoming the translational gap in computational pathology. This mutual comprehension will improve patient care through more accurate and efficient disease diagnosis.

Update on “Cell Therapy” Clinics Offering Treatments of Ocular Conditions Using Direct-To-Consumer Marketing Websites in the U.S.

To assess the scope of U.S.-based companies advertising and administering non-Federal Drug Administration (FDA) approved cell-based therapy (herein called NFACT) for ocular conditions based on information from companies' public websites after the FDA's legal actions against specific NFACT clinics in 2018 and 2019. Current findings are compared to previously published data from 2017. Trend study looking at U.S.-based companies that use direct-to-consumer marketing and have websites advertising therapy for ocular conditions. A systematic and extensive keyword-based Internet search was utilized to identify, document, and analyze U.S. business websites offering NFACT for ocular conditions as of August 2022. Main outcomes measured include, clinic locations, marketed ocular conditions, types of NFACT offered, source of stem cells used, routes of administration, and treatment costs. From the prior analysis in 2017 to the 2019 analysis, there was a decrease in the number of NFACT clinics from 76 to 62 and companies from 40 to 39. Given the concerning persistence of NFACTs in August 2019 an additional analysis was performed in 2022 which showed a drastic decrease in NFACT clinics from 62 in 2019 to 18 in 2023 and from 39 companies to 13 in 2023. In both 2019 and 2022, the most commonly referenced ocular condition was age-related macular degeneration (2019 - 72%, 2022 - 92%). The state with the most clinics was in Texas (2019 - 12; 2022 - 5). Autologous adipose-derived stem cells were the most common cell type used in both analyses. In 2019 U.S.-based direct-to-consumer companies marketing NFACT persisted despite (1) a lack of high-quality clinical evidence supporting the efficacy of these procedures, (2) the association of some of these treatments with severe vision loss, and (3) increasing FDA oversight and recent legal action. In 2022 the number of clinics and companies decreased, but their persistence is a reminder that continued concern is necessary and ophthalmic associations need to continue advocacy efforts to protect patients from these potentially predatory organizations.

Disproportionality Analysis of Nusinersen in the Food and Drug Administration Adverse Event Reporting System: A Real-World Postmarketing Pharmacovigilance Assessment

BackgroundNusinersen is the first drug for precise targeted therapy of spinal muscular atrophy, a rare disease that occurs in one of 10,000 to 20,000 live births. Therefore, thorough and comprehensive reports on the safety of nusinersen in large, real-world populations are necessary. This study aimed to mine the adverse event (AE) signals related to nusinersen through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. MethodsWe extracted reports of AEs with nusinersen as the primary suspect from FAERS between December 2016 and March 2023. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for AE signal detection. ResultsWe extracted a total of 4807 suspected AE cases with nusinersen as the primary suspect from the FAERS database. Among them, 106 positive signals were obtained using the ROR and BCPNN. The highest frequency reported systemic organ class was general disorders and administration site conditions. Common clinical AEs of nusinersen were detected in the FAERS database, such as pneumonia, vomiting, back pain, headache, pyrexia, and post–lumbar puncture syndrome. In addition, we identified potential unexpected serious AEs through disproportionality analysis, including sepsis, seizure, epilepsy, brain injury, cardiorespiratory arrest, and cardiac arrest. ConclusionsAnalyzing large amounts of real-world data from the FAERS database, we identified potential new AEs of nusinersen by disproportionate analysis. It is advantageous for health care professionals and pharmacists to concentrate on effectively managing high-risk AEs of nusinersen, improve medication levels in clinical settings, and uphold patient medication safety.

Keeping patients in the dark: perioperative anesthetic considerations for patients receiving 5-aminolevulinic acid for glioma resection.

5-Aminolevulinic acid hydrochloride (5-ALA), available under the trade name Gleolan, is an orally administered fluorophore drug used to enhance visual differentiation of cancerous tissue from healthy tissue, primarily during surgical resection of high-grade gliomas. Although given preoperatively, 5-ALA has important implications for anesthetic care throughout the perioperative period. This article reviews pharmacology, safety concerns, and perioperative considerations for patients who receive oral 5-ALA. Although approved for clinical use by the United States Food and Drug Administration in 2017, studies and case reports published since then have further delineated side effects of this medication and its mechanisms and pharmacokinetics. Mitigating the possible side effects of 5-ALA requires an understanding of its basic mechanism as well as focused perioperative planning and communication. Administration of this medication may result in nausea and vomiting, photosensitivity, increases in serum concentration of liver enzymes, and hypotension. Patients who receive 5-ALA must be protected from prolonged light exposure during the first 48 h after consumption and administration of other photosensitizing agents should be avoided (Supplemental Video File/Video abstract).