International journal of clinical pharmacology and therapeutics最新文献

Background: Extracorporeal membrane oxygenation (ECMO) provides life support for critically ill tuberculosis (TB) patients. However, during ECMO therapy, significant fluctuations in the plasma concentration of anti-TB drugs occur due to drug adsorption in the ECMO circuit, hemodilution, and metabolic disturbances.

Materials and methods: This single-case study monitored the plasma concentration of anti-TB drugs in a TB patient supported by ECMO.

Results: The differences in peak plasma concentrations (C_max) measured at the end of ECMO support vs. 7 days after ECMO withdrawal were as follows: isoniazid (66%), linezolid (63%), ethambutol (56%), and levofloxacin (12%).

Conclusion: We analyzed ECMO's impact on drug concentrations and implemented therapeutic drug monitoring to optimize therapy. However, this single-case study has inherent limitations; future multi-center studies are warranted to validate these findings.

Introduction: Asthma is a chronic disease that requires careful management, and its exacerbations can be life-threatening. The aim of this study was to ascertain whether inhaled corticosteroids (ICS)-containing inhaler in combination with oral montelukast and levocetirizine could lessen the exacerbation of asthma in comparison to inhaler alone.

Materials and methods: Among 437,915 asthma patients receiving ICS-containing inhaler, 91,122 participants were included. Treatment groups were categorized as (1) ICS-containing inhalers (ICS with or without long-acting β-2 agonist (LABA)), and (2) ICS-containing inhalers used in combination with both oral montelukast and levocetirizine, and (3) severe exacerbation of asthma (visit of emergency room or hospitalization). After 1 : 1 propensity score matching of treatment groups, survival analysis utilizing Cox regression was conducted for estimating the effect of treatment on asthma exacerbation.

Results: We found that the inhaler plus montelukast and levocetirizine group exhibited a lower crude incidence rate and was associated with a lower risk of all-cause death and moderate to severe exacerbation. Specifically, the adjusted hazard ratios (HRs) were 0.71 (p = 0.006) for all-cause death, 0.57 (p < 0.001) for moderate exacerbation. For severe exacerbations, the adjusted HRs were 0.59 for emergency room visits and 0.66 for hospitalizations (p = 0.018 and 0.011, respectively), compared to the ICS-only group, demonstrating a statistically significant reduction.

Conclusion: Treatment with ICS-containing inhaler plus oral montelukast and levocetirizine was significantly associated with a lower risk of exacerbations in asthma patients. Alongside the growing burden of healthcare utilization and costs in South Korea, consideration of the treatment of ICS with montelukast and levocetirizine may serve as an effective treatment option for patients with severe, uncontrolled asthma, potentially improving disease management and reducing healthcare costs.

Hand-foot syndrome (HFS) is a relatively common, dose-limiting dermatologic toxic reaction associated with multiple chemotherapeutic agents, including pegylated liposomal doxorubicin (PLD). Early symptoms of HFS include erythema, marked discomfort, swelling, and tingling on the palms and soles of the feet, which may progress to blistering and even ulceration in severe cases. We report a case of a breast cancer patient who developed HFS after receiving 3 cycles of PLD. The patient presented with redness, swelling, blistering, ulceration, and exudation in her palms, soles, axillae, groin, and waist. After symptomatic treatment, her HFS symptoms were significantly relieved. At the same time, we have also examined the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data for further reports of the relationship between different anthracyclines and risk of HFS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options for the prevention of progression. Relieving swallowing difficulties, reducing breathing difficulties, and alleviating muscle spasms are essential to improving the quality of life in patients with ALS. Many symptoms can be treated clinically with medication; however, the evidence level of related research is relatively low. Rehabilitation management can aid in improving various functional impairments and enhancing quality of life. This review introduces and describes the relevant evaluations of rehabilitation and nonpharmacological symptomatic treatment methods for functional disorders from the perspectives of motor and nonmotor symptoms. This review may promote the popularization of ALS rehabilitation management and provide an additional reference for ALS treatment.

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.

Background: Since its approval by the U.S. Food and Drug Administration in January 2021, vericiguat, a novel soluble guanylate cyclase stimulator, has been increasingly utilized in the treatment of heart failure with reduced ejection fraction. However, comprehensive long-term safety data on vericiguat in large populations are lacking.

Objective: This study analyzed the adverse events reported to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to assess the safety profile of vericiguat.

Materials and methods: We selected four algorithms to evaluate the signals of adverse events related to vericiguat: Multi-item Gamma Poisson Shrinker, Bayesian Confidence Propagation Neural Network, Proportional Reporting Ratio, and Reporting Odds Ratio.

Results: We conducted a retrospective analysis of the FAERS database from January 19, 2021, to December 31, 2024, encompassing 6, 981, 085 reports. Among these, 1,863 adverse events from 886 reports were identified with vericiguat as the primary suspect. After applying all four algorithms at the preferred term level, 64 preferred terms were recognized, encompassing 853 signals. The most common adverse events, such as hypotension, dizziness, dyspepsia, and anemia, were consistent with findings of clinical trials. Additionally, we identified new adverse events, including gastrointestinal hemorrhage and renal impairment.

Conclusion: Our analysis provides a comprehensive safety assessment of vericiguat. Most of these results align with findings from previous studies. In addition, our data revealed several new adverse events. This study provides valuable insights that can inform future research and clinical practice.

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.