International journal of clinical pharmacology and therapeutics最新文献

Background and objectives: The potential association between testosterone therapy and cardiovascular disease remains a topic of debate. While some studies suggest a link between testosterone treatment and heart disease, definitive evidence for a causal relationship is lacking. This study aimed to investigate the causal relationship between testosterone gel use and cardiovascular disease, including stroke, coronary heart disease, hypertension, and cardiomyopathy, using a two-sample Mendelian randomization (MR) approach.

Materials and methods: This study utilized data from Genome-Wide Association Studies and applied MR analysis to assess causal relationships. The primary method was the inverse variance weighted method, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses were conducted to evaluate the robustness of the results.

Results: The inverse variance weighted analysis showed no significant causal link between testosterone gel use and cardiovascular disease risk. Sensitivity analyses revealed no evidence of horizontal pleiotropy or heterogeneity.

Conclusion: The study findings suggest that testosterone treatment does not significantly increase the risk of developing cardiovascular disease.

Objective: Diabetes mellitus (DM) causes various long-term complications and has, e.g., a direct negative effect on bone metabolism. Pioglitazone, which is used to treat DM, increases the risk of fractures. Reduced bone metabolism in patients with DM substantially impairs their quality of life. Therefore, this study aimed to determine the association of fractures with incretin-related drugs, dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients treated with pioglitazone using a pharmacovigilance database.

Materials and methods: Data from the U.S. Food and Drug Administration Adverse Event Reporting System from the first quarter of 2013 to the end of 2019 were analyzed. The reporting odds ratio and information component values were used to evaluate the positive and inverse associations between the abovementioned drugs and fractures.

Results: Inverse associations were observed between incretin-related drugs and fractures in patients treated with DPP-4Is (sitagliptin) and GLP-1RAs (dulaglutide, exenatide, and liraglutide). A subgroup analysis revealed inverse associations between fractures and GLP-1RAs (exenatide and liraglutide) in patients treated with pioglitazone.

Conclusion: Our results suggest that incretin-related drugs, especially GLP-1RAs, reduce the risk of fractures in patients treated with diabetes medications such as pioglitazone.

Objective: To explore the clinical characteristics of dabigatran-induced bleeding and analyze its risk factors in patients with nonvalvular atrial fibrillation (NVAF).

Materials and methods: A retrospective analysis was conducted on patients with NVAF who received 110 mg of dabigatran twice daily from January 2020 to March 2023. Patients were divided into a long-term-use group and a first-time-use group on the basis of their duration of medication use. The impact of long-term dabigatran use on coagulation function was analyzed. Furthermore, patients in the long-term-use group were divided into bleeding and nonbleeding subgroups. Multivariate logistic regression analysis was used to determine the risk factors for bleeding. Clinical data such as underlying diseases, concomitant medications, bleeding types, and bleeding sites were collected.

Results: A total of 531 cases were collected, including 214 in the long-term-use group and 317 in the first-time-use group. In addition to fibrinogen (p > 0.05), coagulation function indicators, including the prothrombin time, prothrombin time percentage, international normalized ratio, activated partial thromboplastin time, and thrombin time (TT), were greater in the long-term-use group than in the first-time-use group, whereas D-dimer values were significantly lower in the long-term-use group (p < 0.05). A total of 63 bleeding cases were found, with an overall bleeding rate of 11.86%. The bleeding type was BARC type 1 (87.30%), and the bleeding site was mainly gastrointestinal bleeding (77.78%). Multivariate logistic regression analysis revealed that a TT value > 116 s (OR 0.385, 95% CI 0.150 - 0.984; p = 0.038) and the presence of heart failure (OR 0.341, 95% CI 0.133 - 0.875; p = 0.025) were risk factors for bleeding in patients on long-term dabigatran therapy.

Conclusion: The probability of bleeding caused by long-term use of dabigatran is relatively high, but it is mainly minor bleeding. The long-term use of dabigatran has an impact on multiple coagulation function indicators. Clinical physicians and pharmacists need to closely monitor patients' TT values and whether they have heart failure and identify high-risk populations for bleeding as early as possible.

Cytomegalovirus is a common opportunistic infection that often affects individuals with impaired immune function. It may present with a variety of clinical manifestations. Treatment for ulcerative colitis (UC) usually requires immunosuppressants and steroids, increasing patients' susceptibility to cytomegalovirus infection. We report the case of a 53-year-old female patient with corticosteroid-resistant UC and recurrent cytomegalovirus infection. The patient had exacerbations, and the diagnosis of cytomegalovirus infection was confirmed through serology and detection of high levels of cytomegalovirus DNA in biopsies using quantitative polymerase chain reaction (PCR). After requiring intravenous ganciclovir, the patient improved. However, she had further relapses requiring treatment with foscarnet, with marked improvement in symptoms and endoscopic results. This case shows the importance of evaluating acute cytomegalovirus infections in patients with corticosteroid resistance. Quantitative PCR appears to be a valuable tool in guiding treatment decisions. In addition, the case is evidence for the satisfactory efficacy of foscarnet in managing cytomegalovirus infections.

Objective: To evaluate the changes in hematological parameters after replacement therapy with either iron dextran or ferumoxytol in patients with iron deficiency.

Materials and methods: We conducted a retrospective review of 246 consecutive patients with iron deficiency treated with a single intravenous (IV) infusion of a fixed dose of 1,025 mg of iron dextran (145 patients) or 1,020 mg of ferumoxytol (101 patients). Laboratory data were collected at baseline and at 2 - 3 months after replacement therapy.

Results: The median hemoglobin (Hb) and ferritin levels pre- and post-iron dextran were 9.5 (95% CI, 9.2 - 10.0) g/dL and 17 (95% CI, 14 - 20) ng/mL, and 12.0 (95% CI, 11.7 - 12.2) g/dL (p < 0.0001) and 123 (95% CI, 98 - 162) ng/mL (p < 0.0001), respectively. The median Hb and ferritin levels pre and post ferumoxytol were 10.4 (95% CI, 9.8 - 10.9) g/dL and 22 (95% CI, 18 - 28) ng/mL, and 12.5 (95% CI, 12.1 - 12.9) g/dL (p < 0.0001) and 129 (95% CI, 90 - 174) ng/mL (p < 0.0001), respectively. No statistically significant difference was observed between iron dextran and ferumoxytol in change of Hb levels, ferritin, transferrin saturation, mean corpuscular volume (MCV), and red cell distribution width (RDW). Transfusion reactions with iron dextran and ferumoxytol were observed in 2 (1.4%) and 3 (3%) patients, respectively (p = 0.65).

Conclusion: In patients with iron deficiency, the change of the hematological parameters after replacement therapy was not statistically different between iron dextran and ferumoxytol. Our data suggests that these two formulations have similar efficacy and safety after the IV administration of equivalent doses.

Hematologic responses (< 1%) to piperacillin/tazobactam were uncommon, and mostly reported in non-pregnant adults. The use of piperacillin/tazobactam during pregnancy is considered to be moderately safe for the human embryo-fetus (pregnancy grade B). However, changes in pharmacokinetics during pregnancy (such as an increase in plasma volume and an increase in renal clearance rate) may alter the toxicity threshold of the drug. This is a case of a pregnant woman (26 weeks of gestation) treated with piperacillin/tazobactam for psoas abscess (Proteus mirabilis). After 22 days, the patient developed low-grade fever, leukopenia, neutropenia, and thrombocytopenia. Three days after discontinuation of piperacillin/tazobactam, the above adverse reactions were all reversed. The Naranjo scale yielded a score of 7, which indicates a definite result for this adverse drug reaction. This was the first report of piperacillin-tazobactam-induced pancytopenia in pregnancy.

Background: Linezolid is classified under the reserve group of antibiotics, and it exerts its antibacterial activity by disrupting protein synthesis. Clinically, linezolid is used for treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). It is eliminated through both renal and hepatic routes. Being a narrow therapeutic index drug, linezolid needs special dosing considerations for safe and effective treatment.

Materials and methods: A plasma concentration dataset of 94 patients with 347 samples was used for development of a population pharmacokinetic model on NONMEM software. The influence of significant covariates on pharmacokinetic parameters was analyzed by stepwise covariate modeling, and dosing simulations were performed on the basis of significant covariates.

Results: The data was best analyzed using a one-compartment model with first-order elimination. The clearance (CL) of linezolid was estimated as 3.38 L/h, while volume of distribution (Vd) was 36 L. The between-subject variability on linezolid CL was 29.8%, and that of Vd was 39.6%. Creatinine clearance (CrCl) and age of the patients were proven to be significant covariates on CL, while no significant covariate was observed for Vd during stepwise covariate modeling. The dosing simulations revealed that a different dose should be administered based on the CrCl of patients.

Conclusion: The renal status and age of the patients are significant covariates responsible for linezolid CL, and a dose of 200, 300, 400, and 600 mg is appropriate for patients with CrCl of 20, 40, 80, and 120 mL/min, respectively.

Objective: To screen differentially expressed genes (DEGs) in triple-negative breast cancer (TNBC) by bioinformatic methods and explore their relationship between TNBC prognosis and related biological functions.

Materials and methods: Microarray dataset GSE65194 was downloaded from Gene Expression Omnibus (GEO) database. The whole TNBC-related datasets were downloaded from The Cancer Genome Atlas (TCGA) database. After screening DEGs in R software, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the function of these DEGs. The survival curve examination of the DEGs was performed based on TCGA database and Kaplan-Meier plotter website. In addition, the gene-drug interaction network was explored using the Comparative Toxicogenomics Database (CTD).

Results: A total of 2,496 up-regulated and 142 down-regulated DEGs were revealed in GEO database and TCGA database simultaneously. The GO and KEGG analysis revealed enrichment in regulation of nucleobase, nucleoside, nucleic acid metabolism, DNA binding, and integrin family cell surface interactions. Furthermore, up-regulation of quinolinate phosphoribosyl transferase (QPRT), member RAS oncogene family (RAB26), and SRP receptor subunit beta (SRPRB) were significantly associated with survival in TNBC patients.

Conclusion: QPRT, RAB26, and SRPRB may be three potential novel prognostic biomarkers for TNBC and will provide potential guidance value for future research on TNBC.

Objective: To investigate the colonization rate of group B Streptococcus (GBS) during the second trimester of pregnancy, the correlation between GBS infection and miscarriage as well as the impact of intervention on pregnancy outcomes.

Materials and methods: 228 GBS-positive pregnant women at 14 - 28 weeks of gestation were divided into 3 groups according to their preferences to receive medical intervention: group A (antibiotic group, n = 54) received oral antibiotic, group B (probiotic group, n = 96) received oral probiotic, and group C (non-intervention group, n = 78) received no drug treatment. 300 GBS-negative pregnant women were selected voluntarily and randomly as the control group (group D). The incidence of miscarriage-related conditions, negative conversion rate of GBS were compared between the 4 groups. Perinatal outcomes were compared between the GBS persistent positive and negative groups.

Results: GBS colonization rate was 14.7%. The incidence of threatened miscarriage and miscarriage in group A were 1.85 and 1.85%, both of which were lower than those in group B at 21.9 and 6.3%, and group C at 33.3 and 7.7%, with all differences being statistically significant (p < 0.05). The incidence of threatened miscarriage and miscarriage in group B and group C were significantly higher than those in group D at 3.3 and 2.7% (p < 0.05). The negative conversion rate of GBS in group A was significantly higher than that in group C (14.8 vs. 2.7%, p < 0.05). There was a difference in the incidence of fetal distress, premature delivery, premature rupture of the fetal membrane, chorioamnionitis, and neonatal infection between the continuously positive and negative pregnant women (p < 0.05).

Conclusion: GBS colonization rate was 14.7% in the second trimester of pregnancy. GBS infection can increase the risk of threatened miscarriage and miscarriage as well as the risk of adverse pregnancy outcomes. Early intervention with antibiotics can increase the negative conversion rate of GBS, reduce the incidence of threatened miscarriage and miscarriage, and ameliorate the adverse outcome of pregnancy. The effect of probiotic intervention on the negative conversion of GBS was insignificant.

Ocrelizumab is a recombinant humanized IgG1 monoclonal antibody that depletes B lymphocytes by binding their surface antigen CD20 and is approved for the relapsing forms of multiple sclerosis (MS). Several studies report that in utero exposure to ocrelizumab is not associated with an increased risk of malformations, and very few cases of neonatal B-cell count depletion are described after therapy ending shortly before conception or during early pregnancy. We report the first case of transient and complete neonatal B-cell depletion, while conception took place 3 months after the last administration.