Effectiveness Of Drugs Research Articles

Drug-Drug Interaction Potential of Mavacamten with Midazolam: Combined Results from Clinical and Model-Based Studies.

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single-center, open-label study in healthy participants. Participants received: on day 1, midazolam 5 mg; on days 2-3, mavacamten 25mg; on days 4-16, mavacamten 15 mg; and on day 17, mavacamten 15 mg and midazolam 5 mg. Plasma concentrations of mavacamten, midazolam, and the midazolam metabolite 1'-hydroxymidazolam were measured. A physiologically based pharmacokinetic (PBPK) model was used to simulate the effect of mavacamten-mediated CYP3A4 induction on midazolam exposure by CYP2C19 phenotype. Thirteen adult participants were enrolled (46.2% were female; mean [SD] age: 34.0 [9.0] years). Compared with midazolam alone, midazolam coadministered with mavacamten decreased the maximum observed plasma concentration (Cmax), area under the drug concentration-time curve (AUC) from time zero to infinity (AUC0-inf), and AUC from time zero to last measurable concentration (AUC0-last) for midazolam by 7%, 13%, and 24%, respectively; for 1'-hydroxymidazolam, AUC0-inf and AUC0-last increased by 20% and 11%, respectively. Ten participants experienced adverse events and the majority were mild in severity. The PBPK model predicted the clinical trial data well. The PBPK simulation assessed that the overall impact of mavacamten on midazolam Cmax and AUC was predicted to be weak regardless of CYP2C19 phenotype. At clinically relevant exposures, mavacamten had a negligible effect on midazolam exposure.

Comprehensive Review of Pharmaceutical Innovations: The Role of Pharmacists in Modern Healthcare Systems

He found that advanced medical drugs are amongst the most defining features of modern healthcare systems, as they offer far better patient results than earlier technologies due to the introduction of distinct new therapies, better treatment of symptoms, and novel administration systems. These changes have also impacted pharmacists' roles, from simple mule dispensers to clinical experts in medication management, patient counseling, and decision-making. It aims to investigate the new pharmacopeia in pharmaceutical technological development and the new role of pharmacists in such changes. The paper discusses the concept of personalized medicine, the place and role of biologics biosimilar, and the increasing function of pharmacists in managing a vast number of related and interconnected processes of pharmacotherapy. Therefore, this paper aims to highlight through a synthesis of prior research, case-study investigations, and concept-based studies the role and contribution of pharmacists, particularly in balancing the therapeutic effectiveness of new drugs while dispersing related risks, adherence, and quality of life.

Drug safety: an integrated approach

Drug safety is a system of established principles and practical recommendations aimed at ensuring the safe and effective use of medicines. The aim of the study was to develop principles and design a conceptual model of drug safety based on a systematic analysis and an integrated approach. Material and methods. Systematic analysis of literary and Internet sources, a systematic approach, logical analysis, graphical method, modeling. Based on the study of the specifics of the existing pharmaceutical market and its participants, the regulatory framework, literary and Internet sources characterizing the circulation of medicines, drug-related problems of patient treatment, ethical norms and rules and system analysis, the principles of drug safety are proposed. The concept of drug safety is considered as a three-dimensional phenomenon requiring an integrated approach. Taking into account the system analysis, a conceptual model of drug safety has been developed, which includes 6 key elements: ensuring the safety of medicines from the state, manufacturers of medicines, medical and pharmaceutical workers, patients, the need for support and training of specialists, as well as directions for their implementation. The external factors influencing the clinical effectiveness of drugs and improving the quality of work of medical and pharmaceutical specialists are shown.

Assessment of tuberculosis drug efficacy using preclinical animal models and in vitro predictive techniques

Tuberculosis (TB) killed approximately 1.3 million people in 2022 and remains a leading cause of death from the bacteria Mycobacterium tuberculosis (M.tb); this number of deaths was surpassed only by COVID-19, caused by the SARS-CoV-2 virus. The alarming emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M.tb strains presents an urgent need for effective new treatments. Our study aimed to determine the synergistic effects of antibiotic combinations against M.tb. Using a high-throughput in vitro checkerboard assay, we evaluated the interactions of Bedaquiline (BDQ) and other antibiotics including Capreomycin (CAP), Linezolid (LIN), and Sutezolid (SUT) against M.tb H37Rv. BDQ and CAP demonstrated in vitro enhanced effect, which prompted further investigation in vivo using the murine low dose aerosol (LDA) model. After aerosol challenge with M.tb, C57BL/6 mice were treated with BDQ, CAP, or their combination, starting 28 days post-infection. The antimicrobial treatment lasted four weeks, and the bacterial burden in lung and spleen tissues was assessed at the end of treatment. At 4 weeks post-treatment, a significant reduction in bacterial load was observed within the lungs and spleens of mice given BDQ alone or given as a BDQ/CAP combination compared to the untreated group. In contrast, CAP monotherapy led to an increase in bacterial load within the lung and no significant difference in bacterial burden in the spleen in comparison to the untreated mice. These results were confirmed in the guinea pig model of TB, where both BDQ and the BDQ/CAP combination treatment led to a decrease in bacterial burden in the lung and spleen, whereas CAP had no significant effect on bacterial burden at the 4-week post treatment timepoint. We next determined whether there may be differences in vitro with the BDQ/CAP combination against M.tb lineages 1, 2 and 4. We determined that in vitro enhanced effect was not observed in some representative strains of M.tb lineage 4, indicating variability in drug effectiveness across M.tb lineages. This research underscores the complexity of TB treatment and the critical need for innovative approaches to combat this global health threat.

Anemia in oncological practice. Eralfon – the optimal opportunity for personalization of drug therapy

Anemia has a noticeable negative impact on the quality of life of cancer patients and determines the prognosis of the disease. The need to treat anemia is determined by its negative impact on life expectancy, since hypoxia caused by anemia can be associated with resistance to chemotherapy, radiation therapy, causes stimulation of genetic mutations and neoangiogenesis in the tumor, which makes it difficult to control it. The methods of correction of anemia are determined by the clinical picture and the antitumor treatment being carried out. The use of blood transfusions is limited and involves a number of risks. Erythropoiesis-stimulating drugs can reduce the need for blood transfusions. The article describes the mechanisms of action, indications and side effects of recombinant erythropoietin (rEPO) drugs. The analysis of the effectiveness of rEPO drugs in the treatment of anemia in oncology based on the historical experience of clinical trials is presented. The recommendations of the leading communities on the use of rEPO drugs in various categories of patients are presented, and the Russian experience of using epoetin alpha in patients receiving chemotherapy is reflected. The use of erythropoietins clearly in accordance with the indications can significantly improve the results of treatment of cancer patients.

Establishment and application of a rapid new detection method for antimicrobial susceptibility testing of Klebsiella pneumoniae based on MALDI-TOF MS.

The earlier appropriate treatment of Klebsiella pneumoniae infections according to the antimicrobial susceptibility profile based on the minimum inhibitory concentration (MIC) has a great clinical benefit. Our objective was to establish a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based antimicrobial susceptibility test (AST) for K. pneumoniae that produces reliable results within a few hours. Our rapid method is similar to the classical turbidity-based microdilution method. We confirmed, theoretically and experimentally, that MALDI-TOF MS can replace the naked eye in judging the results (MICMS) by "seeing" the bacterial growth in the presence of different concentrations of antibiotics, including determination of the lower limit of bacterial count detection (4 × 105 cfu), the optimal period of incubation (2 h), and bacterial growth curve assay. Based on the study mentioned above, we determined the susceptibility of K. pneumoniae to imipenem. The MICMS and MIC data agreed over 85% (40/46) within 1 dilution range. Susceptibility profiles determined with our rapid method and the reference broth microdilution method were also compared. MICMS resulted in 97.9% (45/46) category agreement, 2.2% minor discrepancies, no major discrepancies, and no very major discrepancies. The summarized category agreement resulted in a kappa coefficient of almost 1 for weighted Cohen's kappa, which could be considered a nearly perfect agreement. It took just 2 h to produce a susceptibility profile with a low failure rate using our new rapid AST method, a work day earlier than the broth microdilution method.IMPORTANCEEmpirical antimicrobial use before antimicrobial susceptibility test (AST) is necessary but risks patient harm and excess costs. It is particularly worrying that the inappropriate use of carbapenems has allowed carbapenem-resistant Klebsiella pneumoniae to become the commonest transmissible carbapenem-resistant Enterobacterales worldwide. Guidelines recommend targeted therapy based on minimum inhibitory concentration results, which directly reflect the effectiveness of antibacterial drugs. The gold standard method of AST relies on visible bacterial growth, causing long turnaround times. Current rapid AST techniques are hampered by factors such as high costs, technological complexities, and limited detection capabilities. We present a novel rapid method and applied to the determination of the susceptibility of K. pneumoniae to imipenem. It took just 2 h to produce a susceptibility profile with a low failure rate, a work day earlier than the standard method. Our method is potentially a faster, more precise, cost-efficient, and user-friendly AST method that can enhance the effectiveness of treatment strategies.

Recent progress in topical and transdermal approaches for melanoma treatment.

The global incidence of melanoma, the most lethal form of skin cancer, continues to escalate, emphasizing the urgent need for more effective therapeutic strategies. This review assesses the latest advancements in topical and transdermal drug delivery systems, positioning them as promising alternatives. These systems allow for the direct application of therapeutic agents to tumor sites, enhancing drug effectiveness, improving patient compliance, and reducing systemic toxicity. Specifically, innovations such as nanoparticles, microneedles, and vesicular systems are explored for their potential to optimize topical and localized drug delivery. By incorporating a graphical overview of these drug delivery vehicles, we visually underscore their roles in enhancing therapeutic outcomes across various treatment categories such as chemotherapy, immunotherapy, phototherapy, phytotherapy, and targeted therapy. This article critically evaluates recent breakthroughs, addresses the current challenges faced by researchers, and explores the future directions of topical and transdermal approaches in melanoma management. By presenting a summary of the latest research and predicting future trends, this review aims to inform ongoing developments and encourage further innovation in strategies for treating melanoma.

Biosynthesis, Characterization, and Antibacterial Activity of Gold, Silver, and Bimetallic Nanoparticles Using Annona squamosa L. Leaves

The utilization of nano-sized drug delivery systems in herbal drug delivery systems has a promising future for improving drug effectiveness and overcoming issues connected with herbal medicine. As a consequence, the use of nanocarriers as novel drug delivery systems for the improvement of traditional medicine is critical to combating infectious diseases globally. In line with this, we herein report the biosynthesis of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), and bimetallic nanoparticles (BMNPs) as antibacterial agents against pathogenic bacterial strains using Annona squamosa L. leaf extract as a bio-reductant and bio-stabilizing agent. The as-synthesized metal nanoparticles were characterized by transmission electron microscopy (TEM), ultraviolet–visible (UV–Vis) absorption spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and the dynamic light scattering (DLS) method. The as-synthesized MNPs had an average particle size of 6.98 nm ± 2.86 nm (AgNPs), 21.84 ± 8.72 nm (AuNPs), and 2.05 nm ± 0.76 nm (BMNPs). The as-synthesized AgNPs and BMNPs showed good antibacterial activity against pathogenic bacterial strains of Gram-positive Staphylococcus aureus (ATCC 25923) and Gram-negative Escherichia coli (ATCC 25922). The obtained results offer insight into the development of benign nanoparticles as safe antibacterial agents for antibiotic therapy using Annona squamosa L. leaf extract.

DFT Study of Coordination of N-Monochlorosubstituation Derivatives of Biguanide

Biguanides [HN=C(NR1R2)-NH-C(NR3R4)=NH] constitute an important family of molecules used as drugs in the treatment of diabetes. It is known that some transition metal complexes with given organic compounds deeply increase both therapeutic actions of the metal and the organic compound. The chlorine atom, a preferred substitute in pharmacy, improves the effectiveness of drugs and reduces their side effects. The mesmeric +M effect of the chlorine atom would make it possible to enhance the nucleophilic character of any N-chlorosubstituted nitrogen. In this work a theoretical study of coordination of N-chlorine derivatives of biguanide is carried out mainly at the DFT/B3LYP/6-31G (d, p) level. The Gaussian 09 & 03, HyperChem softwares and the DCENT-QSAR program are used. The coordinating possibility of each ligand were studied analyzing some coordinating indicators as: interatomic bond lengths, atomic charges, molecular electrostatic potentials, frontier orbital structures and electrophilic superdelocalizability. Then, the formation of its complex with zinc (II) has been calculated. The results of the calculations revealed the imine nitrogen atoms as the most favorable coordination sites. Bioactive complexes of these ligands with Zn (II) are modelled. Testing the bioavailability of obtained complexes according to the Lipinski rules of 5, we noticed that they can be considered as drug-candidates.

Overcoming Low Adherence to Chronic Medications by Improving their Effectiveness using a Personalized Second-generation Digital System.

Low adherence to chronic treatment regimens is a significant barrier to improving clinical outcomes in patients with chronic diseases. Low adherence is a result of multiple factors. We review the relevant studies on the prevalence of low adherence and present some potential solutions. This review presents studies on the current measures taken to overcome low adherence, indicating a need for better methods to deal with this problem. The use of first-generation digital systems to improve adherence is mainly based on reminding patients to take their medications, which is one of the reasons they fail to provide a solution for many patients. The establishment of a second-generation artificial intelligence system, which aims to improve the effectiveness of chronic drugs, is described. Improving clinically meaningful outcome measures and disease parameters may increase adherence and improve patients' response to therapy.

Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.

Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments. The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations. The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals. Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities. The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

Leveraging solid solubility and miscibility of etoricoxib in Soluplus® towards manufacturing of 3D printed etoricoxib tablets by additive manufacturing

This research focuses on exploring the solid solubility and miscibility of Etoricoxib, a poorly water-soluble anti-inflammatory drug, within Soluplus®, a polymer used as a matrix for 3D-printed tablets. By utilizing hot-melt extrusion (HME), the drug was dispersed within Soluplus® to enhance its solubility. The extrudates were then employed in 3D printing to create customized solid oral dosage form. This study’s novelty lies in combining HME and 3D printing, aiming to improve drug incorporation, stability, and effectiveness in the final formulation. Comprehensive characterization techniques, including hot stage microscopy (HSM), scanning electron microscopy (SEM), micro-computed tomography (Micro-CT), florescence microscopy, optical microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), solubility studies, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and aqueous solubility study were utilized to elucidate the physicochemical properties, thermal stability, and structural integrity for the extruded filaments (the printing ink), and 3D printed tablets made thereof. Furthermore, the in vitro drug release profile of the 3D printed tablet was systematically evaluated, revealing a controlled drug release pattern from the finished dosage form. The systematic investigation reported herein, starting from theoretical miscibility to the printing ink development through HME, detailed characterization of the extruded filaments, and further solid oral formulation development by additive manufacturing can be utilized as a platform technology or a pathway for the development of personalized medicine with drugs having similar physicochemical properties.

Противоревматическая активность производного амида 3-имидазол-замещенной-4,5-дигидроизоксазолкарбоновой кислоты — ингибитора протеиназа-активированного рецептора II типа

Treatment of rheumatoid arthritis is a complex and time-consuming process that does not always lead to significant results both due to poor effectiveness of drugs and drug toxicity. It means we need to search for new pharmacological targets to influence the pathological process, one of which is inhibition of proteinase-activated receptors 2 (PAR2 receptors) activity. In 2016–2019, synthesis of low-molecular-weight antagonists of PAR2 receptors belonging to 4,5-dihydroisoxazole-5-carboxamide derivatives was carried out, and in 2023 their anti-inflammatory efficacy was examined using the formaldehyde edema model. The most effective laboratory R004 compound was tested on a model of autoimmune pristane-induced inflammation in rats. During treatment of chronic inflammation in rats, R004 inhibited significant development of edema of feet, damage to small joints, and specific changes in the formula of white blood, and according to biochemical blood test led to normalization of liver and kidney functions and energy metabolism. R004 turned out to be more effective and safer than the comparator drugs such as diclofenac sodium and dexamethasone.

Chronic Heart Failure: Focus on Differences Between Men and Women

This review focuses on the sex-related differences of patients in etiological factors, clinical picture, and objective laboratory and instrumental signs of heart failure. The authors performed an analysis of the effectiveness of drug and non-drug treatments depending on the gender of patients with low and preserved left ventricular ejection fraction, which should improve the quality of medical care and outcomes in patients with heart failure.

Nutritionally physiological cell culture medium and 3D culture influence breast tumour proteomics and anti-cancer drug effectiveness

Many drugs have been discontinued during phase II/III breast cancer clinical trials due to lack of clinical efficacy, indicating shortcomings in predictive value of preclinical data. Nutrient availability in the tumour cell microenvironment and the dimensionality of in vitro tumour cells likely impact on drug responsiveness. Global proteomics experiments were conducted to assess the impact of nutrient availability and dimensionality of culture. Protein set enrichment analyses identified “pathways in cancer”, “focal adhesion” and “ECM receptor in interaction” related to cell culture dimensionality in MDA-MB-231 cells. In MCF-7 cells, 4 pathways were influenced by medium composition, and 2 pathways were influenced by cell culture dimensionality (2D vs. 3D). These pathways were also identified using KEGG analyses. Eight drugs were selected for investigation according to the differential expression of their putative or known target proteins. The influence of medium composition on drug effectiveness was explored using the “Melbourne Medium” (MM), developed to have nutritionally physiological levels of metabolites as compared with conventional (hyper-nutritional) cell culture medium (CM). The influence of dimensionality on drug effectiveness was also explored, using an innovative 3D viability assessment combining automated confocal microscopy and image analysis. Dimensionality of culture appeared to have a greater influence on the proteome and drug effects than variation in nutrient levels. The number of differentially expressed proteins in the different media was greater in 2D than 3D. We conclude that the risk of qualifying inactive compounds in preclinical assessment may be mitigated using additional models incorporating physiological media and 3-dimensionality.

Effectiveness and Monitoring of Side Effects of Hypertension Drugs in the Elderly in Kalijaga Village

Hypertension is the disease with the highest prevalence in Indonesia. Prevalence of hypertension in the elderly aged 55-75 years and above, which is 62.63% of the overall percentage of people with hypertension. However, many elderly people are not aware and responsive to the treatment of hypertension. The use of anti-hypertensive drugs is often not taken with good procedures. The purpose of this study was to determine the effectiveness and side effects of anti-hypertensive drugs consumed by the elderly in Kalijaga. Sampling using purposive sampling technique with a sample of 30 respondents with blood pressure criteria ≥140/90 mm Hg. Data analysis used wilcoxon and chi-square tests. The results showed a significant effectiveness after the administration of anti-hypertensive drugs as shown by 26 people reaching the target blood pressure therapy. Many of the side effects felt were derived from the use of anti-hypertensive drugs.

Exploring the enhanced bioactivity and reactivity of novel Fe(III) and Co(II) complexes incorporating sulfadiazine tetradentate ligand: Structural, DFT, molecular docking, and biological applications

This current work presented the synthesis, characterization and bio-evaluation of new Fe(III) (FePSD), and Co(II) (CoPSD) complexes based on N-[4-amino-5-cyano-6-(methylthio)pyridin-2-yl]-3-oxobutanamide in pyridine afford N-(4-amino-5-cyano-6-(methylthio) pyridin-2-yl)-3-oxo-2-([4-(pyrimidin-2-ylsulfamoyl) phenyl]hydrazono) butanamide (PSD). Interestingly, the FePSD and CoPSD complexes exhibit notable stability and solubility in organic solvents, with molar conductivity values of 79.35 Ω−1 cm2 mol−1 for FePSD and 8.89 Ω−1 cm2 mol−1 for CoPSD, indicating a 1:1 electrolytic nature for FePSD and non-electrolytic behavior for CoPSD. FTIR analysis confirmed metal–ligand interactions, as shifts in key bands were observed, while UV–Vis spectra and magnetic moment measurements supported octahedral geometries for both complexes. DFT calculations provided insights into the electronic structure, revealing that CoPSD has higher reactivity and electrophilicity, while FePSD showed moderate reactivity. Thermal and mass spectral analyses further characterized their stoichiometry and stability. The antibacterial and antifungal activities were evaluated against a range of Gram-positive and Gram-negative bacteria and fungal strains. The FePSD and CoPSD complexes demonstrated significantly enhanced antimicrobial efficacy compared to the parent ligand, as evidenced by larger inhibition zones, higher activity indices, and lower minimum inhibition concentrations (MIC). CoPSD exhibited superior antibacterial and antifungal activity compared to FePSD, nearing the effectiveness of standard antibiotics and antifungal drugs. Additionally, the anti-inflammatory potential of these compounds was assessed using the egg albumin denaturation method. Both FePSD and CoPSD showed remarkable inhibition of protein denaturation, surpassing the parent ligand and even outperforming the standard drug Ibuprofen at higher concentrations. The enhancement in biological activity is attributed to the metal chelation effect, which improves cell membrane permeability and reactive oxygen species (ROS) generation. Molecular docking studies further elucidated the binding interactions of PSD, FePSD, and CoPSD with target proteins, revealing stronger hydrophobic interactions and hydrogen bonding in the metal complexes, correlating with their superior biological activity. These findings highlight the potential of FePSD and CoPSD as promising antimicrobial and anti-inflammatory agents.

Comparative Economic and Clinical Utility of Adding Candesartan for Hypertension Management

Introduction: Antihypertensive drugs require high costs because they are used over a long period. Therefore, consideration is needed in drug selection requirements, effectiveness, and price. This study aimed to see the beneficial results of hypertension therapy and the non-medical costs incurred by patients using cost-utility analysis (CUA). Method: This research was a prospective study. The incremental Cost-Utility Ratio (ICUR) of antihypertensive treatment was calculated using cost-utility data obtained through EQ-5D-5L questionnaires from outpatients at Universitas Andalas Hospital in January- March 2023 who met the inclusion and exclusion criteria. The costs used were from a patient perspective, consisting of direct medical and non-medical costs. This study compared standard treatment (amlodipine) with the addition of candesartan. Results: The number of respondents in this study was 67, consisting of 23 respondents (34.33%) using amlodipine alone and 44 respondents (65.67%) using the amlodipine-candesartan combination. The ICUR value obtained was IDR7,318,674/QALY. The difference in the average utility value of the amlodipine-candesartan combination with amlodipine alone is -0.02, and the difference in cost is -IDR12,224. Based on the cost-utility diagram, the amlodipine-candesartan combination group is included in the southwest quadrant (quadrant III), which illustrates that the cost required for the amlodipine-candesartan combination group is lower than the cost of the amlodipine single treatment group and the outcome is also not better (slightly lower or the same). Conclusion: It was recommended to prioritize using amlodipine alone for hypertension management, as it provides similar outcomes to the amlodipine-candesartan combination while incurring lower costs.

Cost Effectiveness of Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with substantial morbidity and mortality. Current international guidelines recommend antiarrhythmic drugs or catheter ablation (CA) as rhythm-control strategies for AF. This study aimed to comprehensively assess economic evaluations (EEs) of the treatment of AF by country income level. Seven electronic databases were systematically searched for EE literature until March 30, 2024, with no constraints on time or language. Two independent reviewers selected the studies, extracted the data, and assessed the quality of the data. Full EEs comparing CA with antiarrhythmic drugs for rhythm-control treatment were included; surgical or rate-control treatments were excluded. The quality of the included articles was assessed using the ECOBIAS checklist. Costs were converted to purchasing power parity US dollars for 2023. A random-effects meta-analysis was applied to pool incremental net benefit (INB) based on a heterogeneity test and its degree (I2 > 25% or Cochran's Q test < 0.1). We also explored heterogeneity and potential publication bias and conducted sensitivity and subgroup analyses. In total, 27 studies across nine countries were eligible, predominantly from high-income countries (n = 25), with a smaller subset from upper-middle-income countries (n = 2). Because of the heterogeneity among the studies, a random-effects model was selected over a fixed-effects model to pool INBs. Most studies (n = 21) favored CA as the cost-effective intervention, yielding an INB of $US23,796 (95% confidence interval [CI] 15,341-32,251) in high-income countries. However, heterogeneity was substantial (I2 = 99.67%). In upper-middle-income countries, the estimated INB was $US18,330 (95% CI - 11,900-48,526). The publication bias results showed no evidence of asymmetrical funnel plots. In this meta-analysis, CA emerged as a cost-effective rhythm-control treatment for AF when compared with antiarrhythmic drugs, particularly in high-income countries. However, economic evidence for upper-middle-income countries is lacking, and no primary evaluations were found for low-middle-income and low-income countries. Further EEs are necessary to expand the understanding of AF treatment globally.

Influence of Gut Microbiota on Drug Metabolism and Therapeutic Efficacy

Background: The natural complex of microorganisms that inhabit the digestive system is estimated to be trillions of bacteria and is known as the gut microbiota. It is now being appreciated more for its involvement in metabolism of drugs, and effects exerted on efficacy and toxicity of drugs. Differences in the composition of the microbiota in the gut cause differences in drug response among people, and therapeutic processes.Objectives: To evaluate the modulation of gut microbiota on drug metabolism and outcome, and analyze the therapeutic outcomes influenced by the microbiome, and to also identify microbial indicators predictive of variable therapeutic outcomes.Study Design: A Cross-Sectional Study.Place and Duration of the Study: Department of Biochemistry, Saidu Medical College, Swat KP – Pakistan from January 2022 to January 2023.Methodology: The current study recruited a sample of 150 patients. The bacterial structure in the gut was investigated using 16S rRNA analysis, and drug metabolism was determined through the blood plasma samples taken at the required time points. Patients were categorized according to their drug efficacy performance, and statistical comparisons were made to evaluate the relationships, accompanied by standard deviations and p-values, respectively, for proper testing of the results’ significanceResults: Among the 150 patients, a higher number of bacterial strains was also associated with better drug outcomes in terms of SD (.35, p &lt; 0.05). The comparison of the rates of metabolism of the drugs between both groups revealed a group difference (SD = 0.28, p = 0.01). They found that those patients who had longer and more complex bacterial signatures had better outcomes from their treatment than patient with less diverse levels of bacteria in their gut.Conclusion: The buy-in of the study is that a direct association between the gut microbiota profile and Drug metabolism efficiency and effectiveness exists. It may also help in identifying biomarkers of microbial origin that may help to improve treatment outcomes, improve compliance with individual treatment plans, and reduce side effects.