Clinical Safety Assessment Research Articles

Pre Clinical Safety Assessment of AYUSH Carctol S through Acute and Sub Chronic Oral Toxicity Study: Safety Assessment of AYUSH Carctol S

AYUSH Carctol S is a coded Ayurvedic compound formulation developed for treatment of cancer. The safety of the test drug was not established in the experimental animals yet, hence the present study was highlighted the same through acute and sub-chronic toxicity studies. The acute oral toxicity study of the test drug was performed in swiss albino mice with a dose of 2600 mg/kg. Similarly, the sub-chronic oral toxicity study was carried out in wistar rats with three different test doses i.e., 180 mg/kg, 900 mg/kg, and 1800 mg/kg. Cage side observations, feed intake, body weight, gross morphology, and necropsy findings of the animals of test drug-treated animals were normal and no mortality was reported in both either study. During the sub-chronic toxicity study, the hematological and biochemical parameters of AYUSH Carctol S-treated animals were found to be non-significant when compared to the control animals. Further, the histopathological analysis of major organs of AYUSH Carctol S 1800 mg/kg treated animals showed no major lesions and treatment-related changes. The test drug was considered to be nontoxic during the acute and sub-chronic oral toxicity studies. The LD50 of AYUSH Carctol S estimated during the acute toxicity was found as 2600 mg/kg and the sub-chronic safety dose i.e., NOAEL is up to 1800 mg/kg.

Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study

IntroductionCancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is...

Clinical Outcomes and Safety Assessment of Flexible Ureteroscopy as an Outpatient Procedure: A Retrospective Single-Center Study.

Nephrolithiasis, or kidney stone disease, is a significant global health issue in urology, requiring effective management strategies. The management of nephrolithiasis through flexible ureteroscopy (fURS) is increasingly gaining acceptance; however, it is associated with significant costs related to consumables, pharmacotherapy, specialized equipment, and general anesthesia (GA). Limited resources and the need to optimize the cost effectiveness ratio have driven the shift to day-case procedures, offering financial and operational benefits and improving patient satisfaction. This outpatient care approach addresses clinical and economic challenges. For same-day discharge, spinal anesthesia (SA) is essential for fURS, as GA does not permit safe immediate discharge. This retrospective study investigates the feasibility of same-day discharge following fURS procedures performed under SA. Analyzing data from 401 patients who underwent 414 fURS procedures between January 2020 and December 2023, this study aims to evaluate whether same-day discharge is a viable option compared to conventional fURS under GA. The primary objectives are to assess the outcomes, including efficacy, stone-free rate (SFR), pain management, and complication rates, in the context of same-day discharge. Additionally, this study seeks to identify patient and kidney stone characteristics that may influence the suitability of one-day fURS under SA. Outcomes will be measured using the Dindo-Clavien (D-C) classification and Visual Analog Scale (VAS) scores post-procedure.

Percutaneous endoscopic interlaminar discectomy for high-grade migrated lumbar disc herniation: clinical efficacy and safety assessment.

This study aimed to assess the clinical effectiveness and safety of percutaneous endoscopic interlaminar discectomy (PEID) in the management of high-grade migrated Lumbar disc herniation (LDH). A total of 328 patients who underwent PEID for high-grade migrated LDH between May 2020 and January 2023 in our hospital were selected. Patients were categorized into high-grade migrated group and low-grade migrated group according to preoperative MRI findings. The preoperative and postoperative evaluations of clinical outcomes, such as Visual Analogue Scale (VAS) for lower backs and legs, Oswestry Disability Index (ODI), and modified MacNab criteria for surgical success, were compared between groups. No statistically significant differences were found in hospitalization time, surgery time, intraoperative hemorrhage, number of intraoperative fluoroscopies, or incision length between the two groups. The lower back and leg VAS scores and ODI exhibited a statistically significant decrease in both groups across all postoperative time intervals. However, the difference between the two groups was not statistically significant. Postoperative nerve root stimulation symptoms were reported in two and three cases in the high-grade migrated group and low-grade migrated group, respectively. One patient in the high-grade migrated group underwent reoperation due to re-herniation at the same segment. There was no significant difference in the rate of excellent-good cases between the two groups, with an overall rate of 94.7%. In treating high-grade migrated disc herniation, PEID offers advantages such as reduced trauma, small incision, quicker recovery and satisfactory clinical safety and efficacy.

A Clinical Safety Assessment of Hybrid Fractional Laser Use at Increased Depths for Facial Skin Rejuvenation

A Clinical Safety Assessment of Hybrid Fractional Laser Use at Increased Depths for Facial Skin Rejuvenation

Sleeve resection with end-to-end anastomosis in the reconstruction of tracheal defects exceeding six rings: a clinical feasibility study and safety assessment.

Reconstruction is always required for tracheal defects and sleeve resection with end-to-end anastomosis is the most common used. The aim of the study was to present surgical techniques and evaluate the outcomes of sleeve resection with end-to-end anastomosis in the reconstruction of tracheal defects exceeding six rings. The study included patients with primary or secondary malignancies and tracheal stenosis from 2014 to 2019, who were treated with sleeve resection exceeding six tracheal rings, and reconstructed with end-to-end anastomosis. Airway status and patient outcomes were the principal follow-up measures. A total of 16 patients were enrolled in the study including three primary tracheal malignancies, 12 invasive thyroid carcinomas and one with tracheal stenosis. The extent of tracheal resection ranged from seven to nine rings, and the primary end-to-end anastomosis was performed in all 16 patients. Performance of tracheostomy or cricothyroidotomy was done in 6 patients with decannulation at a median of 42 days (range, 28-56). No anastomotic dehiscence, infection or bleeding occurred postoperatively, and all 16 patients maintained an unobstructed airway through the end of follow-up. Sleeve resection reconstructed with end-to-end anastomosis can serve as an appropriate therapeutic strategy for the tracheal defects even exceeding six rings. Adequate laryngeal release is the key to surgical success.

Abstract CT108: Phase I data from TENDU101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment

Abstract Synthetic peptides are explored in the clinic in cancer vaccine development for the purpose of inducing tumor-directed T cell responses. Their immunogenicity is dependent on the chosen adjuvant and target organ exposure (lymphoid organs). To improve peptide immunogenicity, we have developed a technology enabling cross-linking of endogenous, pre-existing circulating antibodies (Abs) by employing a three-dimensional chemistry design. Multiple identical tetanus toxin-derived B cell epitopes (MTTEs) are conjugated to synthetically made antigenic tumor peptides intended to induce T cell responses. Here we report the first clinical safety assessment of the vaccine platform in the trial TENDU101 (NCT04701021). The cancer vaccine candidate (TENDU) was designed to include longer synthetic peptides harboring prostate cancer derived epitopes (CD4 and CD8) from PAP and PSMA. The study was a 3+3 design and doses were 40, 400 and 960 microgram in patients with documented recurrent disease after radical prostatectomy. A tetanus toxoid (TTd) containing vaccine boost was followed by TENDU vaccination via subcutaneous injection in the abdomen (4 doses in total with a 2 week interval) in n=9 patients (gr 1, 2, 3.1). For group 3.2 (n=3) TENDU vaccination was administrated in the same arm as the TTd vaccination. Primary objective was safety and secondary objective assessment of immune responses and preliminary anti-tumor responses. A total of 52 adverse events (AEs) were reported, most mild and deemed unrelated to vaccination. Six treatment-related AEs were reported of which 50% were mild transient injection site reactions in a single patient (gr 3.1), and three events of increases in lipase levels in two patients (gr 2). No serious AEs was reported. T cell responses pre/post TENDU were assessed in a total of six patients of which five patients displayed increased response against vaccine-related CD8 and CD4 epitopes (ELISpot). The three patients with the greatest increase in T cell responses were found to display the highest anti-MTTE IgG responses. A trend towards decrease in circulating tumor cells from screening to the end of treatment visit was observed in the patients with the highest levels of anti-MTTE IgGs post TENDU vaccination. There were no trends for decrease in PSA and/or PAP at the end of treatment and follow-up measurements were affected by initiation of radiation and short-term androgen deprivation. The administration of TTd and TENDU to the same anatomical location although spaced in time appeared to negatively influence immune responses to TTd and TENDU. In conclusion, the novel synthetic peptide conjugate vaccine conjugate was found safe with no serious AEs reported and a positive correlation between anti-MTTE and T cell responses was noted in patients when TENDU was administrated in the abdomen. Citation Format: Wolfgang Lilleby, Anna Bergqvist, Aikaterini Nasi, Wenche Rasch, Sara Mangsbo. Phase I data from TENDU101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT108.

Study protocol of a randomized, double-blind, placebo-controlled clinical trial on the efficacy and safety of an Ayurveda formulation (Ayush-SR) in the management of occupational stress among nurses

Abstract BACKGROUND: Work-related stress has been found to have a detrimental effect on the individual’s productivity, quality of work, health, and personal life. Nursing has been identified as an occupation with high stress levels owing to complex job requirements that demand full physical and mental attributes, high responsibility, and job timings. Many Ayurveda interventions have demonstrated adaptogenic properties, and the proposed manuscript presents the design and protocol of the study, an Ayurveda intervention, Ayush-SR, in occupational stress in nurses. OBJECTIVE: To assess the clinical efficacy and safety of Ayurvedic medicine Ayush-SR in the management of occupational stress among nurses. MATERIALS AND METHODS: A prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm study has been designed to enroll a total of 120 nurses from a tertiary hospital in New Delhi, India. They will be screened for occupational stress based on a Professional Life Stress Scale (PLSS) score between 15 and 45, to meet the selection criteria. The participants will be randomized in a 1:1 ratio and allocated to two tabs of either Ayush-SR in the dose of 500 mg or its matching placebo twice a day after food for 90 days. The two-arm intervention comparison study includes a follow-up of 90 days with an assessment at the end of every 30 days. OUTCOME MEASURES: The primary outcome is the change in scores of PLSS. The secondary outcomes include the clinical safety assessment, changes in the scores of Quality of Life (by WHOQOL-BREF), and Manasa Bhava (Ayurveda-based psychobehavioral parameters) factors. Ethics: Ethics approval was taken from the Institutional Ethics Committee following which recruitment commenced in February 2021. Clinical Trial Registration: CTRI/2020/07/2026276 dated 01.07.2020

A Phase 1 Trial of the Safety, Tolerability, and Biological Effects of Intravenous Enadenotucirev (EnAd), a Novel Oncolytic Virus, in Combination with Chemoradiotherapy in Locally Advanced Rectal Cancer (CEDAR)

Novel treatment combinations are required to increase response rates in rectal cancer. EnAd is an intravenous, tumor selective, oncolytic adenovirus with high affinity for malignant colorectal epithelial cells. Pre-clinical evidence of synergy with radiation warranted further clinical evaluation and assessment of safety in combination with chemoradiation (CRT), 25 × 2Gy and concurrent capecitabine. EnAd was escalated using 2 dose levels of viral particles (1 × 1012, 3 × 1012), given Monday, Wednesday, Friday over 3 schedules (pre-CRT, pre & post CRT). Toxicity and efficacy were used as dual end points in escalation decisions. A 2-parameter and 3-parameter logistic Time to Event Continual Reassessment Method (TiTE-CRM) were used estimate the dose-toxicity and dose-efficacy relationship, respectively. Results are shown as probability and 95% credible interval (Cr.I). The dose limiting toxicity (DLT) window was 13 weeks. Patients who had not completed their DLT window at the time of a dose decision were included in the safety analysis but down-weighted according to their follow-up time and amount of IMP received. Efficacy was assessed at 13 weeks using MRI Tumor Regression Grade (mrTRG), where mrTRG 1-2 equals response. The trial (NCT03916510) was conducted in 4 UK centers. A total of 13 patients were enrolled, 12 of whom were evaluable. Median age was 57 (range 31-84), and 10/13 were male. One patient had two G3 adverse events (AE); diarrhea, acute kidney injury. All other adverse events (AEs) were G1 or 2, with no G4/5 events. The most common AE by organ system was gastrointestinal (20.8%, G1). There were two observed DLTs on Dose schedule 3; leg swelling and acute kidney injury. Responses and toxicities increased with escalating schedules of EnAd (Table 1). CEDAR is the first trial to successfully combine an intravenous oncolytic adenovirus with radiation, demonstrating the feasibility and acceptability of this approach, and a new paradigm in radiosensitization in rectal cancer. Within this small Phase I study, EnAd demonstrated an acceptable safety profile with evidence of a higher-than-expected rate of response by mrTRG. Translation analysis of tissue, blood and microbiome for biological correlates of radiation synergy is underway. PsiOxus, CRUK (A24474). University of Oxford.

Mental health considerations for athlete removal from play and return to play planning

Abstract: Introduction: Athletes experience the same mental health disorders as the general population. When mental health symptoms or disorders are experienced more acutely, there may be occasions when the treating team needs to decide if it is in the best interest of the athlete to be removed from the sport environment for treatment and recovery. If an athlete has been away from the sport environment due to mental health symptoms or disorders, the treating team should be deliberate and collaborative in guiding their return. Removal-from-play (RFP) and return-to-play (RTP) decisions involving an athlete who has experienced mental health challenges can be complex. Methods: The literature around athlete mental health was reviewed to explore contributing and mitigating factors to mental health challenges in this population. General psychiatric recovery trajectories for selected mental illnesses were reviewed to inform RTP planning through and beyond illness episodes. The literature related to RFP and RTP for athletes in terms of specific physical factors (concussion and musculoskeletal injury) and mental health factors (specifically, depression, anxiety, and eating disorders) was also reviewed. Results: A scoping overview of athlete- and sport-specific factors yielded a framework that can be used to guide athlete support, RFP and RTP planning through and beyond mental health-related sport interruption. Conclusion: When mental health symptoms and disorders are present, decisions guiding RFP and RTP should be guided by clinical assessment of safety, stability and function. Due to the complex nature of mental disorders and the interaction of sport elements, it is recommended that sports psychiatrists are involved in the assessment and management process.

CardioMotion: identification of functional and structural cardiotoxic liabilities in small molecules through brightfield kinetic imaging.

Cardiovascular toxicity is an important cause of drug failures in the later stages of drug development, early clinical safety assessment, and even postmarket withdrawals. Early-stage in vitro assessment of potential cardiovascular liabilities in the pharmaceutical industry involves assessment of interactions with cardiac ion channels, as well as induced pluripotent stem cell-derived cardiomyocyte-based functional assays, such as calcium flux and multielectrode-array assays. These methods are appropriate for the identification of acute functional cardiotoxicity but structural cardiotoxicity, which manifests effects after chronic exposure, is often only captured in vivo. CardioMotion is a novel, label-free, high throughput, in vitro assay and analysis pipeline which records and assesses the spontaneous beating of cardiomyocytes and identifies compounds which impact beating. This is achieved through the acquisition of brightfield images at a high framerate, combined with an optical flow-based python analysis pipeline which transforms the images into waveform data which are then parameterized. Validation of this assay with a large dataset showed that cardioactive compounds with diverse known direct functional and structural mechanisms-of-action on cardiomyocytes are identified (sensitivity = 72.9%), importantly, known structural cardiotoxins also disrupt cardiomyocyte beating (sensitivity = 86%) in this method. Furthermore, the CardioMotion method presents a high specificity of 82.5%.

E059 A retrospective analysis of the effectiveness & safety of platelet rich plasma injections in primary osteoarthritis in knee joint, in patients attending a tertiary care hospital, Sri Lanka; a cohort study

Abstract Background/Aims Osteoarthritis (OA) is a common, challenging condition and is a leading cause of disability and impaired quality of life in Sri Lanka due to its ageing population and obesity pandemic. Conventional therapies for OA such as non-pharmacological measures, analgesics and surgical interventions have their own limitations. Platelet rich plasma (PRP) has been suggested as a second-line treatment by European Alliance of Associations for Rheumatology (EULAR) for early and moderate OA, which needs further evaluation to prove its efficacy and safety. This is a retrospective analysis of the effectiveness and safety of PRP injections, in a cohort of patients, attending the National Hospital of Sri Lanka for primary knee OA. Methods A total of 33 patients who had been treated with PRP injections were examined immediately prior to injection as well as 3 weeks, 3 months and 6 months later. Details of clinical variables, demographic data, and assessment of efficacy and safety were gathered by the pre-treatment form filled at the routine clinics. Pre-treatment form is comprised of inclusion and exclusion criteria, gender, biochemical investigations, radiological evidences in the knee joint, usage of previous pharmacological and non-pharmacological treatment received by the patient, weight, height and body mass index (BMI). Pain at the site of infection, stiffness, bleeding and local infection were examined as measures of safety. Pain score according to visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score were used as measures of effectiveness. Descriptive statistics was used to present demographic and clinical variables. Friedman test with Wilcoxon signed rank test for pairwise comparisons were used in the analysis of related samples of pain scores and WOMAC scores pre and post PRP therapy in order to assess effectiveness. Results Stiffness following PRP injection was experienced by 8 (24.2%) participants but none of the patients developed pain and bleeding. Median of pain score before PRP injection was 7.00 and it was reduced to 3.00 after 6 months of therapy. Median of WOMAC score before PRP injection was 54.00 and it was reduced to 30.00 after 6 months of therapy. Significant reduction of pain score (p = 0.000) as well as WOMAC score (p = 0.000) was observed. A significant gradual reduction of both pain score and WOMAC score was observed at 3 weeks, 3 months and 6 months post PRP injection (p = 0.000). Conclusion PRP injections had a good safety profile in our study. A similar trend of improvement of knee OA was observed in terms of both pain score and WOMAC score which ensures its effectiveness. However, with a guidance of these data in Sri Lankan patients, a randomized double blinded clinical trial is recommended. Disclosure R.M. Wickramarachchi: None. S. Janagan: None. W. Udeshika: None. G. Chandana: None. Y. Udara: None. S. Fernando: None.

Missed opportunities for suicide prevention in teens with ADHD

Epidemiological evidence links Attention Deficit Hyperactivity Disorder (ADHD) to increased risk of suicide. The research aimed to describe awareness among primary care pediatricians (PCPs) of ADHD as a risk factor for suicide and PCPs’ practices of suicide risk assessment (SRA) and firearms safety assessment (FSA) in teens with ADHD. An online survey was conducted among residents and attendings (N =68, response rate 72%) at an academic medical center. An open-ended question asking respondents to list up to 10 suicide risk factors was followed by Likert-scale items measuring knowledge, attitudes and self-reported practice. Analysis of variance and Pearson correlations were used to assess relationships between physicians’ personal and practice parameters and their SRA and FSA practices. Unprompted, only two doctors mentioned ADHD as a risk factor for suicide. Respondents rated ADHD significantly lower than depression as a factor that would motivate them to perform a clinical assessment of suicide risk and firearm safety; 4.07 (1.62) v 6.49 (0.97), p<0.001 and 4.01 (1.87) v 6.19 (1.22), p<0.001, respectively. Study data set is limited to a single institution and the sample size is small. PCPs are unlikely to recognize ADHD as a risk factor for suicide, and are therefore unlikely to thoroughly assess and intervene to prevent suicide in teens with ADHD.

Preclinical and clinical safety and efficacy assessment of an organic cotton medical device for the management of moderate to heavy urinary incontinence

Urinary incontinence (UI) is a widespread condition affecting about 200 million people worldwide, with women affected more often than men and prevalence increasing with age. UI is a significant health problem that negatively impacts affected women’s well-being, sociality, and productivity. Therefore, seeking medical advice is highly recommended since valid treatment options exist. However, a definitive solution to the problem is not always possible. In these cases, absorbent containment products can help women deal with the persistent symptoms of incontinence, minimising the effects on the quality of life. High-quality products are paramount to avoid or reduce the onset of irritating skin phenomena, which can sometimes lead to more serious consequences, such as skin infections. Cotton is a natural fibre characterised by softness and hypoallergenic properties that has already shown its ability to improve skin health when used as a component of pads and other absorbent containment products. The aim of this work was to assess the safety and efficacy of a new organic cotton pull-on absorbent product in reducing skin erythema and oedema in women suffering from moderate to heavy urinary incontinence. In-vitro and clinical studies were performed. Results showed that the tested product effectively reduces skin erythema and oedema caused by the conventional use of synthetic pull-on absorbent products. Moreover, good compliance with the use was demonstrated compared to a non-cotton competitor device available on the market. In conclusion, the organic cotton absorbent device tested has improved the quality of life of women suffering from moderate to heavy urinary incontinence.

Evaluation of levocetirizine in beagle dog and cynomolgus monkey telemetry assays: Defining the no QTc effect profile by timepoint and concentration-QTc analysis.

In prior clinical studies, levocetirizine (LEVO) has demonstrated no effect on ventricular repolarization (QTc intervals), therefore it is a relevant negative control to assess in nonclinical assays to define low proarrhythmic risk. LEVO was tested in beagle dog and cynomolgus monkey (nonhuman primate [NHP]) telemetry models to understand the nonclinical-clinical translation of this negative control. One oral dose of vehicle, LEVO (10mg/kg/species) or moxifloxacin (MOXI; 30 mg/kg/dog; 80 mg/kg/NHP) was administered to instrumented animals (N=8/species) using a cross-over dosing design; MOXI was the in-study positive control. Corrected QT interval values (QTcI) were calculated using an individual animal correction factor. Blood samples were taken for drug exposure during telemetry and for pharmacokinetic (PK) analysis (same animals; different day) for exposure-response (C-QTc) modeling. Statistical analysis of QTc-by-timepoint data showed that LEVO treatment was consistent with vehicle, thus no effect on ventricular repolarization was observed over 24 h in both species. PK analysis indicated that LEVO-maximum concentration levels in dogs (range: 12,300-20,100 ng/ml) and NHPs (range: 4090-12,700 ng/ml) were ≥4-fold higher than supratherapeutic drug levels in clinical QTc studies. Slope analysis values in dogs (0.00019 ms/ng/ml) and NHPs (0.00016 ms/ng/ml) were similar to the human C-QTc relationship and indicated no relationship between QTc intervals and plasma levels of LEVO. MOXI treatment caused QTc interval prolongation (dog: 18 ms; NHP: 29 ms). The characterization of LEVO in these non-rodent telemetry studies further demonstrates the value and impact of the in vivo QTc assay to define a "no QTc effect" profile and support clinical safety assessment.

Suprachoroidal injection of polyzwitterion hydrogel for treating glaucoma

Glaucoma is the primary cause of irreversible blindness worldwide. The current treatments are primarily based on drug usage or surgical operation to reduce intraocular pressure (IOP). However, it is expensive and requires patients to insist on taking the medicine for a long time. The suprachoroidal space (SCS) is the space between the choroid and the sclera, which forms part of the uveovortex pathway in the circulation of aqueous humor. So far, it is still challenging to realize the injection of hydrogels into the SCS with long-term duration. In this work, an in situ-forming polyzwitterionic polycarboxybetaine hydrogel is designed and injected to expand SCS to increase the drainage of aqueous humor from the eye via the uveovortex pathway, thus reducing IOP for at least 6 weeks, while commercial hyaluronic acid hydrogel can only last for about 4 weeks. The clinical ophthalmological safety assessment examination shows that the treatment of polyzwitterion hydrogel is well-tolerated that leads to minimal inflammatory reaction, and histopathology assessment demonstrates that the SCS is expanded after injection of the hydrogel. Further analysis of ultrasound biomicroscopy reveals that there is a strong correlation between IOP reduction and SCS expansion. In short, the polyzwitterion hydrogel developed in this work can prolong the period of IOP reduction by expanding SCS, thus treating ocular hypertension and glaucoma without resorting to drugs or regular surgery.

Understanding the Pharmacology of COVID-19 mRNA Vaccines: Playing Dice with the Spike?

Coronavirus disease-19 (COVID-19) mRNA vaccines are the mainstays of mass vaccination campaigns in most Western countries. However, the emergency conditions in which their development took place made it impossible to fully characterize their effects and mechanism of action. Here, we summarize and discuss available evidence indicating that COVID-19 mRNA vaccines better reflect pharmaceutical drugs than conventional vaccines, as they do not contain antigens but an active SARS-CoV-2 S protein mRNA, representing at the same time an active principle and a prodrug, which upon intracellular translation results in the endogenous production of the SARS-CoV-2 S protein. Both vaccine-derived SARS-CoV-2 S protein mRNA and the resulting S protein exhibit a complex pharmacology and undergo systemic disposition. Defining COVID-19 mRNA vaccines as pharmaceutical drugs has straightforward implications for their pharmacodynamic, pharmacokinetic, clinical and post-marketing safety assessment. Only an accurate characterization of COVID-19 mRNA vaccines as pharmaceutical drugs will guarantee a safe, rational and individualized use of these products.

Characterization and comparison of efficacy and safety of calcipotriene and clobetasol in severe chronic plaque psoriasis patients

Calcipotriene and Clobetasol ointments efficiently treat psoriasis. The purpose of the study was to characterize and compare the efficacy and safety of Calcipotriene and Clobetasol in chronic plaque psoriasis patients. 70 patients with chronic plaque psoriasis were recruited and randomly divided into two groups of 35 each. One group received 0.005% Calcipotriene, and the other group received 0.05% clobetasol twice daily for 12 weeks. Efficacy evaluations comprise global improvement assessed by the clinician by using the Physician Global Assessment (PGA) score. Efficacy further included the 'Dermatological Sum Score' (DSS) and Psoriasis Area and Severity Index (PASI) score at each study visit. The safety evaluations included clinical assessment of cutaneous safety and assessment of cutaneous discomfort by the clinician as well as the subject. Calcipotriene and Clobetasol were significantly effective in reducing PASI and DSS. However, the two experimental groups have shown no statistically significant observations. The PGA score assessed clinically was 1.27 for calcitriene and 1.79 for Clobetasol (p&gt;0.05). The cutaneous safety score was higher in the clobetasol group compared to the Calcipotriene group. 4% of cutaneous discomfort was reported with Clobetasol compared to 2% with Calcipotriene. Calcipotriene showed a better safety profile than Clobetasol.

Emerging strategies in nanotechnology to treat respiratory tract infections: realizing current trends for future clinical perspectives

A boom in respiratory tract infection cases has inflicted a socio-economic burden on the healthcare system worldwide, especially in developing countries. Limited alternative therapeutic options have posed a major threat to human health. Nanotechnology has brought an immense breakthrough in the pharmaceutical industry in a jiffy. The vast applications of nanotechnology ranging from early diagnosis to treatment strategies are employed for respiratory tract infections. The research avenues explored a multitude of nanosystems for effective drug delivery to the target site and combating the issues laid through multidrug resistance and protective niches of the bacteria. In this review a brief introduction to respiratory diseases and multifaceted barriers imposed by bacterial infections are enlightened. The manuscript reviewed different nanosystems, i.e. liposomes, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, nanogels, and metallic (gold and silver) which enhanced bactericidal effects, prevented biofilm formation, improved mucus penetration, and site-specific delivery. Moreover, most of the nanotechnology-based recent research is in a preclinical and clinical experimental stage and safety assessment is still challenging.

Efficacy and Safety of Ferric Carboxymaltose in the Management of Iron Deficiency Anemia: A Multi-Center Real-World Study from India.

BackgroundParenteral iron preparations, like ferric carboxymaltose (FCM), are commonly used to manage moderate-to-severe iron deficiency anemia (IDA). Real-world data on efficacy and safety of FCM is limited in India.MethodsA retrospective, observational and real-world study was conducted to assess the efficacy and safety of FCM in adolescents and adults with IDA across 269 centers in India. Data was retrieved from medical records of patients who received FCM for management of IDA. Physicians’ clinical assessment of efficacy and safety of FCM was also assessed. Data were analyzed for hematological parameters at baseline and at 4 ± 1 week for study population, and for severity of anemia.ResultsIn 1800 patients with IDA, intravenous FCM resulted in a significant increase in hemoglobin (Hb) of 2.76 g/dL, serum ferritin of 35.85 µg/L, red blood cell (RBC) count, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) (P < 0.001 for all) at 4 ± 1 week as compared to baseline. In subjects with severe IDA, an increase in Hb was of 3.31 g/dL, serum ferritin increased of 35.84 µg/L, RBC count, hematocrit and MCH improved significantly (P < 0.001 for all). In subjects with moderate IDA, Hb (increase of 2.63 g/dL), serum ferritin (increase of 35.92 µg/L), RBC count, hematocrit, MCV, and MCH improved significantly (P < 0.001 for all). In subjects with mild IDA, only the mean Hb values at 4 weeks were significantly higher (P < 0.001; increased by 1.89 g/dL). Physicians rated efficacy of FCM as very good to good in 97.5% of patients. Similarly, safety of FCM was rated very good to good in 97.2% subjects.ConclusionFCM efficiently, safely and quickly corrects moderate-to-severe anemia in Indian patients in a short span of 4 weeks. Physicians’ positive clinical impression of efficacy and safety supports clinical usage of FCM in real-world scenario.