Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: Anemia is a prevalent complication in chronic kidney disease (CKD) that remains challenging to manage effectively. Daprodustat was recently approved for anemia in CKD. This meta-analysis aims to provide evidence-based insights for the clinical use of daprodustat in CKD-related anemia.

Method: A systematic review and meta-analysis were conducted in accordance with the PRISMA 2020 guidelines, with searches conducted in databases such as PubMed and ClinicalTrials.gov, encompassing studies published up to August 30, 2024. Data from 12 randomized controlled trials involving 9,278 CKD patients (both dialysis-dependent (DD) and non-dialysis-dependent (NDD)) were analyzed.

Results: Daprodustat significantly increased hemoglobin (Hb) levels compared to placebo in both NDD (MD = 1.92, 95% CI [0.67, 3.02], p = 0.001) and DD (MD = 1.72, 95% CI [0.34, 3.65], p = 0.01) patients. However, no significant difference in Hb levels was observed between daprodustat and recombinant human erythropoietin (rhEPO) (MD = 0.05, 95% CI [-0.10, 0.21], p = 0.50). Daprodustat improved iron metabolism by significantly lowering hepcidin and increasing total ironbinding capacity (TIBC) compared to rhEPO. Cardiovascular safety analysis showed no significant difference in major adverse cardiovascular events (MACE) between daprodustat and rhEPO (RR = 1.02, 95% CI [0.92, 1.14], p = 0.83), though a significant reduction in MACE incidence was observed in DD patients (RR = 0.98, 95% CI [0.87, 1.15], p = 0.02). Serious adverse events were significantly lower with daprodustat compared to rhEPO (RR = 0.82, 95% CI [0.66, 0.84], p = 0.02 in DD; RR = 0.61, 95% CI [0.48, 0.78], p = 0.008 in NDD patients).

Conclusion: Daprodustat offers a promising alternative to traditional anemia treatments in CKD, with efficacy comparable to rhEPO and a favorable cardiovascular safety profile, which marks its potential as a valuable therapeutic option.

Introduction: Antimicrobial Resistance (AMR) poses a significant global health threat, leading to increased morbidity, mortality, and healthcare costs. Intensive Care Units (ICUs) are particularly susceptible to AMR due to frequent invasive procedures, extended hospital stays, and the selective pressure exerted by broad-spectrum antibiotics. This review aims to shed light on the current landscape of antibiotic resistance within ICUs of Saudi hospitals. It also explores molecular patterns of bacterial resistance and identifies potential strategies to address this issue. Additionally, it discusses the challenges in implementing these strategies within the Saudi healthcare system.

Methods: We conducted a literature search across electronic databases, including Web of Science, PubMed, EMBASE, Scopus, and Google Scholar, until September 30th, 2024, to identify relevant studies. Selected studies were analyzed to extract insights into prevailing bacterial resistance trends in Saudi ICUs and the molecular mechanisms responsible.

Results: Our findings provide an overview of the current state of AMR in Saudi ICUs, including the emergence and prevalence of specific molecular patterns of bacterial resistance. Moreover, it presents potential strategies to combat antibiotic resistance, including antimicrobial stewardship programs, infection control measures, and the development of new antibiotics. It also highlights the inherent challenges in implementing these strategies within the unique healthcare landscape of Saudi Arabia.

Discussion: The increasing emergence and spread of MDR bacteria in Saudi Arabia are attributed to the unoptimized antibiotic use, over-the-counter antibiotics without prescription, a high volume of international travellers, and challenges in adherence to infection control practices. Addressing the challenges and implementing effective prevention strategies are critical to maintaining antibiotic efficacy and combating AMR. Several strategies have been employed by the National AMR Committee, in partnership with WHO, to address antibiotic resistance in intensive care units.

Conclusion: AMR in Saudi ICUs is a pressing concern requiring immediate attention. A multifaceted approach combining surveillance, education, and policy interventions is essential to overcome this issue. Addressing AMR is crucial for global efforts to preserve the efficacy of antibiotics and maintain the effectiveness of critical healthcare interventions.

Introduction: Treatment-Resistant Depression (TRD) is a complex clinical condition characterized by inadequate response to conventional antidepressant treatments. There is growing evidence that microRNAs (miRNAs) play a role in the underlying pathophysiology of TRD and may offer new avenues for diagnostics and therapy.

Methods: A structured literature review of peer-reviewed publications indexed in PubMed, Scopus, and Web of Science was conducted. The search strategy included combinations of keywords such as "treatment- resistant depression," "microRNAs," "biomarkers," and "miRNA-based interventions." Articles were selected based on relevance to miRNA expression patterns in TRD, therapeutic modulation, and their clinical potential.

Results: Dysregulation of several miRNAs-including miR-135a, miR-34a, and miR-155-was consistently observed in patients with TRD. These miRNAs were linked to impaired synaptic plasticity and persistent neuroinflammation. Therapeutic approaches using miRNA mimics or inhibitors showed potential in restoring neurobiological balance and enhancing response to traditional antidepressants. However, delivery system limitations and blood-brain barrier penetration remain significant challenges.

Discussion: miRNAs appear to play a dual role in TRD, serving both as biomarkers for diagnosis and as targets for novel therapies. Integrating miRNA profiling into clinical workflows could enhance diagnostic precision and guide individualized treatment strategies. Translational barriers, such as delivery specificity and standardization of detection protocols, must be addressed before the widespread clinical application of this technology.

Conclusion: This review highlights miRNAs as promising diagnostic and therapeutic tools in TRD. Continued advancements in delivery systems and validation of biomarker panels may pave the way for their clinical implementation in personalized psychiatry.

Introduction: Obesity is a condition that affects a large part of the global population, and especially in the Western world, leading to a significant systemic inflammatory response in the body, characterized by modification of the secretory inflammatory cytokines and adipokines. The combination of fat accumulation and inflammation can lead to concomitant conditions, such as Insulin Resistance (IR) and increased production and release of fatty acids, ultimately enhancing the occurrence of conditions like metabolic and cardiovascular disorders, with inflammation and oxidative stress being implicated in these phenomena and appearing as important interconnecting factors. In this review, an attempt is made to analyze, in terms of their full scope of action, the pharmaceutical approaches against obesity, which affect fats, sugars, adipokines, and also the central nervous system.

Methods: Using data from experimental animal procedures and clinical trials, the involvement of anti-obesity drugs against systemic chronic inflammation and oxidative stress, as well as in obesityrelated cardiometabolic disorders, is analyzed.

Results: Anti-obesity treatments targeting more than one factor at the mechanistic level and limiting the body's inflammatory responses could contribute in multiple ways to improving metabolic and cardiovascular conditions and derangements. However, they carry a high risk of adverse effects, which may be reduced with the combination of such treatments, leading to a more favorable activity- to-hazard ratio and elucidation of the complete mechanistic properties of these treatments.

Discussion: Until now, many gaps in the literature remain concerning one or more of these aspects for all these treatments. Through the prism of the multi-functional nature of these compounds, an attempt is made to clarify the multi-level nature of action of these substances against obesity, potentially allowing limiting the multi-drug treatment of these conditions, leading to the limitation of interactions, and the multiple side effects related to the drug combination.

Conclusion: In order to achieve the above-mentioned objectives, in addition to investigating the full range of action of these anti-obesity drug treatments, the full history of their dose-dependent side effects and contraindications is required, through further clinical studies and analyses. These findings will shed light on the complete anti-inflammatory, antioxidant, and metabolic changes that anti-obesity treatments could offer, and the clinical manipulation of conditions associated with obesity, since the current misalignment and, in some cases, the mixed results between the already existing research groups lead to less definite conclusions.

Introduction: Small fiber neuropathy (SFN) affects pain and autonomic function, and there is increasing evidence that immune pathways are linked to its pathology. Intravenous immunoglobulin (IVIG) has been proposed as a treatment option for patients with painful SFN but has yielded mixed results. This review evaluates the effectiveness of IVIGs in the treatment of painful SFN.

Methods: According to PRISMA guidelines, a thorough literature search was conducted using five major electronic databases (PubMed, Google Scholar, Scopus, EMBASE, and Web of Science) up to August 17, 2023. Data extraction was performed independently by two reviewers, and quality assessments were performed using Joanna Briggs Institute tools. The PRISMA guidelines ensured the transparency of the review.

Results: This systematic review included seven studies to evaluate the effectiveness of IVIG for the treatment of SFN. The review included 458 patients from various studies conducted between 2005 and 2023, covering various neuropathy subtypes such as idiopathic SFN, sarcoidosis-associated SFN, etc. Both double-blind RCTs reported no significant differences between IVIG and placebo in neuropathy severity or pain reduction. Retrospective cohort studies varied in quality and produced mixed results. Of note, some studies showed significant pain reduction with IVIG, while others did not. The effectiveness of IVIG on neuropathy severity and intraepidermal nerve fiber density was similarly variable, with some studies reporting efficacy and others indicate no significant changes. Overall, IVIG showed potential benefits, but the results were inconsistent across studies.

Discussion: IVIG shows potential efficacy in select SFN subtypes, particularly autoimmuneassociated forms (e.g., TS-HDS/FGFR-3 positive), with some retrospective studies reporting pain and functional improvements. However, two high-quality RCTs found no significant benefit over placebo. Marked heterogeneity in study design, IVIG protocols, diagnostic criteria, and outcome measures limits comparability and generalizability. Adverse events, including infusion reactions were common. These findings highlight IVIG's possible role in immunologically mediated SFN but underscore the need for standardized protocols, biomarker-based patient selection, and large, wellcontrolled trials to establish definitive efficacy.

Conclusion: Some evidence suggests the potential benefit of IVIG therapy for certain subgroups of patients with SFN. However, the overall effectiveness is still unclear, and further studies are needed.

Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is one of the main anticancer drugs, used for the treatment of various malignancies. However, clinical application of this drug is associated with various side effects, prominently nephrotoxicity. One of the promising tools to decrease the side effects of the drug and simultaneously improve its therapeutic effects is the loading the drug into nanoparticles (NPs). This literature review focuses on the efficacy of various types of NPs, such as liposome, micelle, dendrimer, poly (lactic-co-glycolic acid), chitosan, alginate, curcumin (CUR), and metallic NPs to improve the therapeutic effects of CDDP and to decrease the nephrotoxicity. The results of these studies demonstrated that the reviewed NPs are able to decrease the nephrotoxic effects of CDDP in one of four different ways, including as a conjugating agent, encapsulating agent, antioxidant agent, or nanocarrier. Finally, among these reviewed NPs, liposomal NPs and the co-treatment with CUR as an antioxidant agent have more promising effects in reducing the toxicity of CDDP. Overall, the wide use of nanoliposomes in drug delivery systems due to their high stability, biocompatibility, drug loading capacity, and high bioavailability prompts the authors to propose liposomal CDDP delivery as a potent candidate for future studies. Moreover, because of the synergistic effects of CUR and CDDP on cancerous cells, the antioxidative properties of CUR in mitigating CDDP-induced nephrotoxicity, and the radiosensitizing influence of CUR, there is potential for the co-delivery of CDDP and CUR via liposomes to the tumor region.

Background/objective: Type 2 diabetes mellitus (T2DM) increases the risk of fractures and its effects on bone health. The impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on bone fracture risk is unclear. We performed a network meta-analysis (NMA) to assess the impact of DPP-4i on fracture risk in patients with T2DM.

Methods: A comprehensive systematic literature search was conducted on PubMed/Medline, Cochrane Library, and ClinicalTrials.gov until June 2024 to identify RCTs reporting fracture events with DPP-4i among T2DM patients. A Bayesian NMA has been performed to calculate the odds ratio (OR) and 95% credible intervals (CrI). Surface under the cumulative ranking analysis (SUCRA) was utilized to assess the rank probability of DPP-4i.

Results: A total of 85 RCTs were identified, including 89,965 T2DM patients with 1,083 fracture events. In the direct meta-analysis, DPP-4i did not elevate fracture risk compared to placebo or other oral anti-diabetics (OADs) (OR (95%CI): 1.04 (0.91-1.18); p=0.57 and 1.18 (0.79-1.74); p=0.96, respectively). Alogliptin and sitagliptin indicated a non-significant trend towards reducing fracture risk compared to placebo (OR (95%CI): 0.59 (0.31-1.15); p=0.12) and OADs (OR (95%CI): 0.73 (0.41-1.30); p=0.28), respectively. In the NMA, alogliptin significantly reduced fracture risk compared to linagliptin and SGLT2i (OR (95%CrI): 0.41 (0.16-0.93) and 0.16 (0.017-0.83), respectively). Conversely, linagliptin increased fracture risk compared to sulfonylurea (OR (95%CrI): 2.3 (1.1-5.2)). According to SUCRA, alogliptin (84%) ranked as the preferred treatment for reducing fracture risk in T2DM patients.

Conclusion: Overall, DPP-4i was not associated with an increased risk of fractures in patients with T2DM. However, alogliptin demonstrated a reduced risk of fractures when compared to both linagliptin and SGLT2i. Further long-term clinical studies are needed to confirm the present findings.

Background and aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. It is associated with life-threatening conditions such as cardiovascular disease and hepatocellular carcinoma. This systematic review and meta-analysis aimed to evaluate ezetimibe in patients with NAFLD.

Methods: A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to August 8th, 2024, to identify relevant articles. The most used keywords for searching are "Ezetimibe" and "Nonalcoholic Fatty Liver Disease." A random-effects model evaluated the standardized mean difference (SMD) and its 95% confidence interval (CI). All analyses were performed using the "meta" package in the R programming language version 4.3.1.

Results: Ten studies included in our study (five non-controlled and five controlled trials, with a total of 516 participants) investigated the effect of ezetimibe on different parameters. Ezetimibe significantly improves AST (SMD: -0.63, 95% CI: [-1.12, -0.14]), ALT (SMD: -0.50, 95% CI: [-0.91, -0.10]), GGT (SMD: -0.30, 95% CI: [-0.49, -0.10]), and LDL (SMD: -0.85, 95% CI: [-1.16, -0.54]), but was unable to improve HDL, TG, and BMI. Ezetimibe was also able to improve steatosis (SMD: -0.30, 95% CI: [-0.49, -0.10]), but inflammation (SMD: 0.06, 95% CI: [-0.57, 0.69]), ballooning (SMD: -0.62, 95% CI: [-1.55, 0.31]), and fibrosis (SMD: 0.03, 95% CI: [-0.25, 0.31]) were not improved.

Conclusion: Based on the findings, the administration of ezetimibe can reduce liver enzymes as well as the hepatic steatosis, but its effects on liver inflammation and fibrosis remain controversial. Further research is required to study its effects in combination with other treatments.