Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline.

Marburg virus disease (MVD) presents a significant global health threat, lacking effective antivirals and with current supportive care offering limited therapeutic options. This mini review explores the emerging landscape of novel antiviral strategies against MVD, focusing on promising therapeutics currently in the development pipeline. We delve into direct-acting antiviral approaches, including small molecule inhibitors targeting viral entry, replication, and assembly, alongside nucleic acid antisense and RNA interference strategies. Host-targeting antivirals are also considered, encompassing immune modulators like interferons and cytokine/chemokine modulators, broad-spectrum antivirals, and convalescent plasma and antibody-based therapies. The paper then examines preclinical and clinical development for the novel therapeutics, highlighting in vitro and in vivo models for antiviral evaluation, safety and efficacy assessments, and the critical stages of clinical trials. Recognizing the challenges of drug resistance and viral escape, the mini review underscores the potential of combination therapy strategies and emphasizes the need for rapid diagnostic tools to optimize treatment initiation. Finally, we discuss the importance of public health preparedness and equitable access to these promising therapeutics in achieving effective MVD control and global health security. This mini review presents a comprehensive overview of the burgeoning field of MVD antivirals, highlighting the potential of these novel approaches to reshape the future of MVD treatment and prevention.

Solid Self-Nanoemulsifying Drug Delivery Systems of Furosemide: In Vivo Proof of Concept for Enhanced Predictable Therapeutic Response.

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 µL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 µL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

Assessment of drug utilization pattern of antimicrobial agents in hospitalized patients with Infectious Diseases: A cross-sectional study in the United Arab Emirates.

Efficacious use of antimicrobial agents (AMAs) is paramount to combat a wide range of infections, ensure patient safety, and reduce antimicrobial resistance. To assess the drug utilization patterns of AMAs in hospitalized patients with infectious diseases in a secondary care hospital. A prospective observational study was conducted for 6 months in the internal medicine department. Data were collected, antimicrobial prescription patterns were screened, and drug utilization was assessed using the anatomical therapeutic chemical/defined daily dose methodology. Furthermore, predictors of the prescription of multiple AMAs were also analyzed. A total of 146 patient case records were reviewed and 285 AMAs were prescribed during the study period with a mean patient age of 54.2 ± 24.4 years. The average number of antimicrobials administered per patient was 1.94 ± 0.94. Respiratory tract infection and urinary tract infection were the common indications, and penicillins were the most prescribed class of AMAs. Multivariate analysis showed that the presence of comorbidities (P < 0.05) and longer hospital stays (P < 0.0001) increased the likelihood of prescribing multiple AMAs. The study provides insight into the pattern of prescribing of AMAs which help to improve the quality of care. Prescribing AMAs by generics and from the hospital formulary list according to the recommendations of the World Health Organization is a good sign of clinical practice. The study signifies the need to continuously monitor AMAs to optimize drug therapy and enhance the quality of drug use in clinical practice.

Assessment of the scope, completeness, and consistency of various drug information resources related to COVID-19 medications in pregnancy and lactation.

BACKGROUND: Drug use in pregnancy and lactation is challenging. It becomes more challenging in pregnant and lactating women with certain critical clinical conditions such as COVID-19, because of inconsistent drug safety data. Therefore, we aimed to evaluate the various drug information resources for the scope, completeness, and consistency of the information related to COVID-19 medications in pregnancy and lactation. METHODS: Data related to COVID-19 medications from various drug information resources such as text references, subscription databases, and free online tools were used for the comparison. The congregated data were analyzed for scope, completeness, and consistency. RESULTS: Scope scores were highest for Portable Electronic Physician Information Database (PEPID), Up-to-date, and drugs.com compared to other resources. The overall completeness scores were higher for Micromedex and drugs.com (p < 0.05 compared to all other resources). The inter-reliability analysis for overall components by Fleiss kappa among all the resources was found to be 'slight' (k < 0.20, p < 0.0001). The information related to the older drugs in most of the resources, provides in-depth details on various components such as pregnancy safety, clinical data related to lactation, the effect of the drug distribution into breast milk, reproductive potential/infertility risk and the pregnancy category/recommendations. However, the information related to these components for newer drugs was superficial and incomplete, with insufficient data and inconclusive evidence, which is a statistically significant observation. The strength of observer agreement for the various COVID-19 medications ranged from poor to fair and moderate for the various recommendation categories studied. CONCLUSION: This study reports discrepancies in the information related to pregnancy, lactation, drug level, reproductive risk, and pregnancy recommendations among the resources directing to refer to more than one resource for information about the safe and quality use of medications in this special population.The present study also emphasizes the need for development of comprehensive, evidence-based, and precise information guide that can promote safe and effective drug use in this special population.

The Effect of Polymers on Drug Release Kinetics in Nanoemulsion In Situ Gel Formulation.

Glaucoma is an ocular condition characterized by elevated intraocular pressure (IOP). Conventional treatments of glaucoma face poor corneal permeability and bioavailability. To address these issues, a nanoemulsion in situ gel of Timolol maleate was developed in this study by adding the polymer Carbopol 934p. Using Carbopol 934p, a novel ophthalmic pH-induced nanoemulsion in situ gel was formulated. The formulation was liquid at pH 4 and quickly gelled when the pH was raised to 7.4 (Lacrimal pH). The pH-triggered in situ gelling mechanism demonstrated continuous drug release over a 24 h cycle. A total of nine trial formulations were prepared (NEI1-NEI9) and subjected to various physicochemical and in vitro evaluations. According to the in vitro release kinetics, the drug release of Timolol maleate nanoemulsion in situ gel NEI5 followed zero-order kinetics, with a release exponent value of 0.902, indicating that the mechanism of release was non-Fickian diffusion regulated. In vivo results showed that Timolol maleate nanoemulsion in situ gel NEI5 provided a better-sustained release of the drug, compared with the Timolet OD eye drops. The formulation is stable in storage, with no distinguishable change in appearance, physical properties, quality, and percentage drug release. NEI5 also reduces drug administration frequency, which improves patient compliance. Timolol maleate nanoemulsion in situ gel NEI5 achieved the goal of controlled drug delivery with extended-release and cost-effectiveness, lowering the dosage and frequency of drug administration, and thus may improve patient compliance. In conclusion, the stable nanoemulsion in situ gel of Timolol maleate NEI5 decreases intraocular pressure (IOP) over a prolonged period.

Potential Psychotropic and COVID-19 Drug Interactions: A Comparison of Integrated Evidence From Six Database Programs.

Background Drug interactions are a significant issue in mental illnesses and coronavirus disease 2019 (COVID-19) infections. Inconsistency in drug interaction resources makes prescribing challenging for healthcare professionals. To assess the scope, completeness, and consistency of drug-drug interactions (DDIs) between psychotropic and COVID-19 medications in six specific drug information (DI) databases. Methodology For the comparison, six DI resources were used: Portable Electronic Physician Information Database, Micromedex®, Medscape.com, UpToDate®, Drugs.com drug interaction checker, and WebMD.com drug interaction checker. Using the Statistical Package for the Social Sciences (SPSS) software version 27 (IBM Corp., Armonk, NY), the gathered data were examined for scope, completeness, and consistency. Results Scope scores were higher for PEPID© than all the other resources (p < 0.001) for each comparison. PEPID© had better overall completeness scores (median 5, Interquartile range [IQR] 5 to 5; p<0.05 for each comparison), except for Drugs.com (p < 0.05 for each comparison), and were more remarkable for Micromedex® (median 5, IQR 5 to 5). The Fleiss kappa scores among the six different DI sources were poor (k < 0.20, p < 0.05) for the category of information related to clinical effects and level of documentation, moderate agreement (k = 0.4 - 0.6, p < 0.05) for the severity and course of action of DDIs, and fair agreement (k = 0.4 - 0.6, p < 0.05) for mechanism. Conclusion A comprehensive, accurate information among DI resources is essential for healthcare professionals that will significantly impact patient care in the clinical practice. Banking on high-quality resources will help healthcare professionals to make an informed decision while prescribing to avoid inappropriate combinations that can adversely affect patient outcomes.

Assessment of clinical pharmacist interventions in drug therapy in patients with diabetes mellitus in a tertiary care teaching hospital.

AIM: To assess the impact of clinical pharmacist interventions in drug therapy in hospitalized patients with diabetes mellitus. METHODS: A Prospective interventional study was carried out in the medicine wards of a tertiary care teaching hospital over a period of 10 months from September 2013 to June 2014. The drug therapy details of the patients were collected from inpatient case records in the respective clinical wards. Clinical pharmacist reviewed the drug therapy, identified the drug related problems during ward rounds and discussed with the physicians and suitable suggestions was provided which had been documented. RESULTS: A total of 189 drug therapy problems were identified from 151 patient case records. The number of drug related problems was found to more in males than females. Drug related problems were commonly seen in patients aged between 61 and 70 years of age. The most common drug related problems was found to be drug use without indication (17.98%) followed by improper drug selection (16.40%). The most frequent suggestions by the clinical pharmacist were on cessation of drug (30.68%). The acceptance rate of suggestions and the changes in drug therapy was found to be high (58.20%). The majority of the level of significance of drug related problems was seen to have moderate significance in grade. CONCLUSION: Involvement of clinical pharmacist as a member of healthcare team during ward rounds in hospitalized patients with diabetes mellitus helps in identification and prevention of drug related problems which will helps to rationalize drug therapy, achieve better therapeutic outcomes and improved patient care.