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.

Pharmacokinetics and Pharmacodynamics of a Nanostructured Lipid Carrier Co-Encapsulating Artemether and miRNA for Mitigating Cerebral Malaria.

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood-brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

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 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 Pharmacist's Role in Managing COVID-19 in Chronic Kidney Disease Patients: A Review of Existing Strategies and Future Implications.

The global burden of the COVID-19 pandemic has not only disrupted healthcare delivery but has also compromised patients' access to healthcare on account of the scarcity of medications and trained healthcare professionals. COVID-19 has been particularly challenging for patient subpopulations constituting immunocompromised individuals, geriatric patients, and those afflicted by chronic ailments. Reports indicate that diminished kidney function in chronic kidney disease (CKD) renders patients highly susceptible to complications during COVID-19 treatment. Pharmacists, being medication experts, have a significant role in making treatment decisions during COVID-19 infection. This article describes pharmacists' interventions for monitoring and managing COVID-19 in patients with CKD. Given the massive increase in off-label use of medications to treat COVID-19, pharmacists can contribute substantially towards dosing decisions, reporting adverse medication events, and managing drug-drug interactions in COVID-19 patients suffering from CKD. In addition to traditional methods of delivering their services, the pharmacist should also adopt innovative tele-health systems to optimize patient care and ensure that patients receive safe and effective therapy during the pandemic.

Assessment of potential drug interactions among psychiatric inpatients receiving antipsychotic therapy of a secondary care hospital, United Arab Emirates.

The majority of the antipsychotic drugs are also known to interact with other co-administered drugs. Drug-drug interaction (DDI) reports among patients receiving antipsychotic medications are common. The study aims to identify the potential drug-drug, drug-tobacco, and drug-ethanol interactions associated with antipsychotics and significant predictors of potential DDIs (pDDIs). A prospective observational study was conducted among psychiatric inpatients receiving antipsychotic therapy and met the inclusion criteria that were reviewed for the presence of pDDIs using DRUGDEX-Micromedex database 2.0. The identified pDDIs were graded according to the severity and type of documentation. A total of 110 patients had a minimum of a single interaction, and the overall frequency of pDDIs reported was 64.7%. Of 158 pDDIs, 92 interactions (58.2%) were of major severity, while 66 interactions were of moderate severity (41.8%). Olanzapine with valproate (40 [25.3%]) was the most commonly documented pDDIs, followed by risperidone with valproate (20 [12.6%]). Olanzapine with tobacco (20 [69%]) was the most common drug-tobacco interaction. Simultaneously, olanzapine with ethanol was the most common potential drug and ethanol interaction (9 [50%]). Variables such as the number of drugs and polypharmacy statistically significantly predicted pDDIs (F[7, 162] = 8.155, P < 0.05, R2 = 0.26). Knowing the severity of different pDDIs will help clinicians and prescribers monitor patient safety through regular monitoring for interactions and adverse drug effects in future. The number of medications and polypharmacy was found to be the most significant predictor of pDDIs.

Intensive monitoring of adverse drug reactions in nephrology unit of tertiary care teaching hospital.

Adverse drug reactions (ADRs) are one of the common causes of morbidity and mortality. Renal insufficiency is considered as one of the risk factors for the development of ADR. The study determined the occurrence of ADRs in patients with renal failure and their incidence of hospital admission. The study also evaluated the nature and severity of ADRs. This was a prospective study conducted in the nephrology unit at a tertiary care teaching hospital for a period of nine months. Patients receiving regular hemodialysis and those either referred or admitted to the nephrology ward were included. ADRs were intensively monitored throughout the study. The causality of suspected ADRs was assessed with the WHO probability scale, Naranjo algorithm, and Karch and Lasagna's scale. The predictability and preventability of ADRs were also determined. A total of 45 ADRs were identified in 369 patients; incidence was 12.19%. Nine ADRs (20%) needed hospitalization. A total of 27 (60%) and 17 (37.8%) ADRs were found to be probable and possible, respectively when assessed by the WHO probability scale. On the contrary, 33 (73.3%) and 26 (57.8%) ADRs were possible in causality when assessed by Karch and Lasagna's scale and Naranjo scale, respectively. Most of the ADRs [26 (57.8%)] were predictable in nature. A wide range of ADRs was noticed in patients with renal impairment, and our study has systematically assessed the nature and severity of ADRs.

Frequency and Predisposing Factors for Drug-Induced Hypoglycemia in Patients with Type-2 Diabetes Mellitus.

OBJECTIVE: Hypoglycemia is the most common complication of the treatment for diabetes mellitus. Various factors predispose an individual for drug-induced hypoglycemia. The aim of this study was to explore the relative frequency and likely predisposing factors for drug-induced hypoglycemia among type-2 diabetic patients in the United Arab Emirates (UAE). METHODS: In this cross-sectional survey-based study which was conducted from February to April 2018 in two local community pharmacies in the UAE, diabetic patients underwent a structured interview on their diabetes mellitus status and management and specific open-ended questions related to hypoglycemic symptoms that they might have experienced and the occurrence of symptoms. Collected data were used to estimate the relative frequency of drug-induced hypoglycemia and to identify the probable predisposing factors and their contribution in causing hypoglycemia using relative risk, Chi-square test, and Fisher's exact test. FINDINGS: The relative frequency of drug-induced hypoglycemia in our study was 46.25%. Patients' age of ≥65 years, duration of diabetes mellitus for more than 1 year, patients with more than one comorbid condition, and patients using more than one antidiabetic medication were predisposing for developing drug-induced hypoglycemia. CONCLUSION: The relative frequency of drug-induced hypoglycemia in a nontrial environment which lacks the special cares routinely provided in drug development clinical trials is high. We suggest that more attention should be paid to identify, prevent, and manage drug-induced hypoglycemia in type-2 diabetic patients who have more than 1 year of diabetes, more than one comorbidity, using more than one antidiabetic medication, and elderly.

Assessment of Potential Drug-Drug Interactions in Hospitalized Cardiac Patients of a Secondary Care Hospital in the United Arab Emirates.

OBJECTIVE: To identify the types, severity, and documentation grades of potential drug-drug interactions (pDDIs) and to identify the predictors of pDDIs among hospitalized cardiac patients. METHODS: This was a cross-sectional study. All the patients who were admitted for >24 h in a cardiology ward of a general hospital of the United Arab Emirates and prescribed with cardiac medications were included. The occurrence of any pDDI between cardiac medications and other coprescribed medications was identified using Micromedex database 2.0® and graded and documented based on the severity and documentation. FINDINGS: A total of 842 pDDIs were identified in 155 patients. The overall relevant frequency for the occurrence of pDDIs was found to be 87.74%. A total of 79 pairs of pDDIs were identified. Among identified pDDIs, 41.33% and 56.65% were major and moderate severity type, respectively, whereas 12.32% were excellent and 36.81% were good documentation grade. The majority of pDDIs were between aspirin-bisoprolol (11.64%). Patients taking more than seven drugs (odds ratio [OR] = 9.90; 95% confidence interval [CI]: 2.28-42.99), polypharmacy (OR = 3.86; 95% CI: 0.93-16.08), and number of medical conditions (OR 0.25; 95% CI: 0.09-0.68) were significant predictors of pDDIs. CONCLUSION: The study fosters the importance of regular and close monitoring for pDDIs among cardiac patients. Thus, multicenter interventional studies are required to determine the exact nature and types of pDDIs in the local population.

Assessment of Perception, Experience, and Information-seeking Behavior of the Public of Ras Al-Khaimah, United Arab Emirates, Toward Usage and Safety of Complementary and Alternative Medicine.

AIMS AND OBJECTIVES: This study was conducted to identify the different types of complementary and alternative medicine (CAM) used, reasons for the use of CAM, and the perceptions, experience, and information seeking-behavior toward usage and safety of CAM by the general public of Ras Al-Khaimah, UAE. MATERIALS AND METHODS: This was a prospective cross-sectional study. A validated, self-administered, or interviewer-assisted survey questionnaire was used to collect the data. Data from 403 respondents satisfying inclusion criteria were collected and were analyzed using the Statistical Package for the Social Sciences version 24.0. RESULTS: A majority of the respondents (218 [54.1%]) were females. The most commonly (210 [52.1%]) used CAM among the study respondents was herbal medicine. A total of 91 (22.6%) of the survey respondents mentioned that they receive conventional medications along with their CAM. Majority (213 [52.9%]) of the survey respondents opted for CAM to prevent illness. Good number (208 [51.6%]) of the survey respondents mentioned that CAM usage was beneficial in improving their health condition, and they (216 [53.6%]) do believe it as safe and effective. However, a small group (26 [6%]) of respondents reported side effects or complications with the use of CAM. CONCLUSION: Widespread use of CAM for different medical problems was evident in our study. Although majority of the CAM users believe it as safe and effective, CAM usage should be discussed with the health-care providers to understand the safety issues involved in the use of majority of CAM.

Monitoring of adverse drug reactions in psychiatry outpatient department of a Secondary Care Hospital of Ras Al Khaimah, UAE.

BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, resulting in increased healthcare cost. Association of psychotropic medications with ADRs is common. Pharmacovigilance can play a vital role in alerting the healthcare providers from the possible ADRs and thus protecting the patients receiving psychotropic medications. AIM: To monitor and report the incidence and nature of ADRs in psychiatry outpatient department (OPD). MATERIALS AND METHODS: A prospective observational study was carried out in the psychiatry OPD. All the patients attending psychiatry outpatient and satisfying the inclusion criteria were monitored for ADRs. The causality, severity and preventability assessment of documented ADRs was done. Chi-square test was done to identify the association between ADRs and sociodemographic, disease and treatment-related variables. Paired Student's t-test was carried out to compare the significance difference in the weight of the patients who reported weight gain to psychotropic medications. RESULTS: The incidence rate of ADR was found to be 10.2%. A total of 112 ADRs were documented. Weight gain 18 (16.07%) followed by somnolence 8 (7.14%) was the most commonly reported ADR. Atypical antipsychotics 37 (33.0%) were the most common class of psychotropic drugs implicated in ADRs. Escitalopram 16 (14.28%) followed by quetiapine 14 (12.5%) were associated with a maximum number of ADRs. No significant association (P > 0.05) documented between demographic and treatment-related variables with number of ADRs. CONCLUSION: Study revealed a moderate incidence of ADRs in patients attending the psychiatry OPD. Majority of the ADRs reported during the study were mild in nature and not preventable type.

Assessment of prevalence of hypovitaminosis D in multiethnic population of the United Arab Emirates.

United Arab Emirates (UAE) has a high prevalence of hypovitaminosis D. Not much data are available regarding the prevalence of Vitamin D deficiency among multiethnic UAE adult population. (1) To determine the prevalence of hypovitaminosis D in multiethnic UAE population (2) To compare the Vitamin D status in Arab and non-Arab population (3) To identify the demographic variables associated with hypovitaminosis D. It was a retrospective study conducted at a secondary care hospital. Electronic case records of all the subjects who had checked their Vitamin D levels during the time period of May 2010-October 2012 were considered for the study. Vitamin D severe deficiency, deficiency, insufficiency, and sufficiency were defined as serum 25-hydroxy Vitamin D (25(OH)D) levels < 10 ng/mL, 10-20 ng/mL, 21-30 ng/mL, and > 30 ng/mL, respectively. A total 425 subjects were included for the data analysis. Vitamin D deficiency was diagnosed in 208 (48.9%) subjects followed by severe Vitamin D deficiency and insufficiency in 141 (33.2%) and 63 (14.8%) subjects, respectively. The overall prevalence of hypovitaminosis D was 96.9%. Negative association (r = -0.196, P < 0.01) was observed between body mass index (BMI) and 25(OH)D levels. Ethnicity was not (P = 0.103) a predictor of 25(OH)D levels. Majority of our study subjects had Vitamin D deficiency. There was no substantial difference in 25(OH)D levels of different ethnic groups. Female gender, age, and BMI were the predictors 25(OH)D levels.

Influences on Malaysian pharmacy students' career preferences.

OBJECTIVES: To identify and evaluate factors affecting the career preferences of fourth-year bachelor of pharmacy (BPharm) students in Malaysia in the presence of a 4-year period of mandatory government service. METHODS: A validated self-administered questionnaire was used in this cross-sectional study to collect data from final-year BPharm students enrolled at 3 government-funded universities and 1 private university in Malaysia. Both descriptive and inferential statistics were used for data analysis. RESULTS: Three hundred fourteen students responded (213 from public universities and 101 from the private university). Approximately 32% of public university students and 37% of private university students ranked their own interest in pharmacy as the reason for undertaking pharmacy degree studies; 40.4% of public and 19.8% of private university respondents stated that they would enter a nonpharmacy-related career upon graduation if given the choice. Public university students ranked hospital pharmacy as their choice of first career setting (4.39, p = 0.001), while private students ranked community pharmacy first (4.1, p = 0.002). On a scale of 1 to 5, salary received the highest mean score (3.9 and 4.0, p = 0.854) as the extrinsic factor most influencing their career choice. CONCLUSIONS: Final-year students at Malaysian public universities were most interested in hospital pharmacy practice as their first career step upon graduation, while private university students were most interested in community pharmacy. The top 3 extrinsic factors rated as significant in selecting a career destination were salary, benefits, and geographical location.