Precision arrows: Navigating breast cancer with nanotechnology siRNA.

Nanotechnology-based drug delivery systems, including siRNA, present an innovative approach to treating breast cancer, which disproportionately affects women. These systems enable personalized and targeted therapies, adept at managing drug resistance and minimizing off-target effects. This review delves into the current landscape of nanotechnology-derived siRNA transport systems for breast cancer treatment, discussing their mechanisms of action, preclinical and clinical research, therapeutic applications, challenges, and future prospects. Emphasis is placed on the importance of targeted delivery and precise gene silencing in improving therapeutic efficacy and patient outcomes. The review addresses specific hurdles such as specificity, biodistribution, immunological reactions, and regulatory approval, offering potential solutions and avenues for future research. SiRNA drug delivery systems hold promise in revolutionizing cancer care and improving patient outcomes, but realizing their full potential necessitates ongoing research, innovation, and collaboration. Understanding the intricacies of siRNA delivery mechanisms is pivotal for designing effective cancer treatments, overcoming challenges, and advancing siRNA-based therapies for various diseases, including cancer. The article provides a comprehensive review of the methods involved in siRNA transport for therapeutic applications, particularly in cancer treatment, elucidating the complex journey of siRNA molecules from extracellular space to intracellular targets. Key mechanisms such as endocytosis, receptor-mediated uptake, and membrane fusion are explored, alongside innovative delivery vehicles and technologies that enhance siRNA delivery efficiency. Moreover, the article discusses challenges and opportunities in the field, including issues related to specificity, biodistribution, immune response, and clinical translation. By comprehending the mechanisms of siRNA delivery, researchers can design and develop more effective siRNA-based therapies for various diseases, including cancer.

Development and validation of standardized severity rating scale to assess the consistency of drug-drug interaction severity among various drug information resources.

BACKGROUND: The consistency in reporting the severity of drug interactions across the drug information resources is important in guiding the appropriate clinical use of drug-pairs, to minimize the associated adverse events. This necessitates the need of a standardized severity rating scale, that can accommodate the different severity ratings of the same interacting drug-pair into a reasonable severity category, that can ease the consistency assessment among different drug information resources. OBJECTIVE: To develop and validate a standardized severity rating scale that can ease the consistency assessment among the various drug information resources. METHODS: The definitions of various severity rating categories as documented in the eight drug information resources was consolidated to develop a standardized severity rating scale. Thus developed rating scale was validated using twenty commonly used drug-pairs. Fleiss' kappa score was used as an indicator for assessing overall consistency among various drug information resources, whereas, Cohen's kappa was used as an indicator of level of consistency between two drug information resources and between individual drug information resource and newly developed standardized severity rating scale. RESULTS: The newly developed standardized severity rating scale classifies the severity of drug-drug interactions into three categories namely mild, moderate and major. The Fleiss' kappa score was improved from 0.047 to 0.176, indicating improved strength of agreement [Average pairwise agreement: 16% Vs 36.7%] among various drug information resources. The average pairwise Cohen's kappa was 0.082 [Strength of agreement: poor] in original severity ratings whereas it was improved to 0.198 [Strength of agreement: almost equal to fair] in standardized severity rating scale. CONCLUSION: The newly developed standardized severity rating scale can be used as a tool to assess the consistency of severity rating categories among the various drug information resources.

Assessing Consistency of Drug-Drug Interaction-Related Information Across Various Drug Information Resources.

Background Information related to drug-drug interactions (DDIs) varies significantly from one drug information (DI) resource to another. These variations pose challenges for healthcare professionals in making the right decisions regarding using some of the drug combinations in needy patients. The objective of this study was to review eight different DI resources for scope, completeness, and consistency of information related to DDIs. Methodology A total of eight DI resources, namely, Micromedex®, Portable Electronic Physician Information Database©, UpToDate®, Medscape.com drug interaction checker, Drugs.com drug interaction checker, Stockley's Drug Interactions (ninth edition, 2010), Drug Interactions Analysis & Management: Facts and Comparisons 2014 (ninth edition, 2014), and the drug interaction appendix of the British National Formulary-76, were compared. Each DI resource was scored for scope by calculating the percentage of interactions that had an entry in each resource. A completeness score was calculated for each resource describing severity, clinical effects, mechanism, and DDI management. The consistency of the information was assessed using Fleiss Kappa (k) score estimated using ReCal3 0.1 (alpha) web service and Statistical Package for the Social Sciences version 24. Results The scope score was the highest (100%) for UpToDate® and Portable Electronic Physician Information Database©, whereas the completeness score was the highest (100%) for Drug Interaction Analysis & Management: Facts and comparisons 2014. The inter-source reliability scores among the eight different DI sources were poor (k < 0.20, p < 0.05) for documentation of information related to severity, clinical effects, mechanism, and management of DDIs. Conclusions Variations in the information cause uncertainty among healthcare professionals concerning interacting drug pairs in clinical practice. This may also increase the possibility of adverse drug outcomes when interacting drug pairs are used in at-risk patients. We recommend comprehensive preventive and management strategies for DDIs depending on a uniform scale of severity and clinical effects across various DI resources.

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.

Prevalence and associations of moderately increased albuminuria in patients with type 2 diabetes in United Arab Emirates.

BACKGROUND AND AIMS: Our study sought to investigate the prevalence of moderately increased albuminuria in United Arab Emirates (UAE) nationals with type 2 diabetes, and to identify the associated factors. METHODS: This prospective cross-sectional study was conducted in two hundred and seven UAE nationals with type 2 diabetes mellitus attending the internal medicine department of a secondary care hospital. Moderately increased albuminuria was estimated in random spot urine samples and was defined as urinary albumin-to-creatinine ratio (UACR) of 3-30 mg/mmoL. Prevalence and associations of moderately increased albuminuria were evaluated. RESULTS: The study population had a mean UACR of 7.2 ± 10.2 mg/mmoL with mean eGFR of 94.5 ± 11.7 mL/min/1.73 m2. Prevalence of moderately increased albuminuria in our study population was found to be 44.0%. Multivariate logistic regression analysis showed that duration of diabetes (OR:1.72, 95% CI:1.34-2.19; p<0.001), presence of hypertension (OR:3.42, 95% CI:0.96-12.20; p=0.050) and neuropathy (OR:2.85, 95% CI:1.03-7.84; p=0.042), BMI (OR:1.08, 95% CI:1.01-1.16; p=0.019), HbA1c (OR:1.39, 95% CI:1.00-1.93; p=0.045), CRP (OR:1.10, 95% CI:1.00-1.22; p=0.035), serum creatinine (OR:1.04, 95% CI:1.02-1.06; p<0.001) and HDL-C (OR:0.10, 95% CI:0.01-0.28; p<0.001) were independently correlated with moderately increased albuminuria. Stepwise multiple linear regression analysis demonstrated that duration of diabetes, HbA1c, CRP and serum creatinine were independent predictors of UACR. CONCLUSION: We report a high prevalence of moderately increased albuminuria in UAE nationals with type 2 diabetes in a secondary care setting. Routine screening and timely management of moderately increased albuminuria in type 2 diabetes mellitus can lead to better patient outcomes.

Impact of pharmacists' intervention on identification and management of drug-drug interactions in an intensive care setting

<p><b>INTRODUCTION</b>The primary and secondary objectives of this study were to identify and assess the risks associated with the occurrence of drug-drug interactions (DDIs) and to determine the value of pharmacists' interventions in the management of clinically significant DDIs, respectively.</p><p><b>METHODS</b>A prospective, case-control study was carried out on patients admitted to the intensive care unit (ICU), and involved a review of patients' medication chart daily by the pharmacist and the clinical parameters. All identified DDIs were carefully analysed in order to provide recommendations on the management of clinically significant DDIs.</p><p><b>RESULTS</b>The majority of DDIs were categorised as Type-C severity level (n = 305, 75.9%). 'Substitution' was recommended in 34 cases of clinically significant DDIs, 'dosage adjustment' in 17 (4.2%) and 'stop or avoid' in 13 (3.2%). The number of drugs prescribed (p = 0.001, rS = 0.539) and length of ICU stay (p = 0.001, rS = 0.364) were significantly associated and positively correlated with the occurrence of DDIs. Patients with DDIs had a longer length of ICU stay than those without DDIs (9.5 days vs. 2.4 days, p = 0.001). No significant difference was found between patients aged below 50 years and those above 50 years (odds ratio 0.488, 95% confidence interval 0.166-1.434) in terms of the risk of DDIs.</p><p><b>CONCLUSION</b>A large number of DDIs were identified in this study, but only a small number were clinically significant. Pharmacists' participation in daily ward rounds could play an important role in the detection and management of clinically significant DDIs.</p>