European Journal of Clinical Pharmacology最新文献

Purpose: This study aimed to describe the role and perceptions of clinical pharmacologists (CPs) in conducting economic evaluations of health technologies within the Spanish National Health System from a healthcare provider perspective.

Methods: We conducted a cross-sectional descriptive study using an online survey distributed to members of the Spanish Society of Clinical Pharmacology between September 2024 and September 2025. Eligible participants were CPs working within or linked to the Spanish National Health System. The questionnaire included four sections addressing respondent characteristics, direct involvement in economic evaluations, economic evaluations conducted by other professionals, and training and opinions. Data were analyzed using descriptive statistics.

Results: Of 106 eligible CPs working within or linked to the Spanish National Health System, 48 completed the survey (response rate: 45.3%). The mean age was 51 years, and 56.3% were women. More than half of respondents (54.2%) reported conducting or having conducted economic evaluations, mainly cost-effectiveness and cost-minimisation analyses, often in collaboration with other healthcare professionals. Results were integrated into care protocols in 15 cases, although follow-up and outcome verification were performed in 7 cases. Among CPs not directly involved, 63.7% reported that economic evaluations are conducted at their centres by other professionals. Despite 91.7% of respondents considered that economic evaluation of health technologies is an activity that should be conducted in their centres, and all considered that a CP should participate in these evaluations, only 35.4% felt sufficiently trained, while 77.1% expressed interest in further training.

Conclusion: Among the surveyed CPs, there is active involvement and a high level of motivation to participate in economic evaluations of health technologies in Spain. Strengthening training opportunities and collaborative networks could enhance their contribution to value-based healthcare.

Background: Hydroxychloroquine (HCQ) usage in COVID patients was a popular topic of study, especially during the first wave of the pandemic. However, the long-term impact of HCQ therapy on infected COVID-19 patients remains unclear.

Objectives: Holding a PROSPERO registration (CRD42025113906), this study aimed to investigate the impact of long-term treatment with HCQ in patients with autoimmune diseases on mortality, as well as on the development of disease-related complications.

Methods: A comprehensive search was conducted across multiple databases. Full-text reports were included for clinical trials and observational studies on adult patients with autoimmune disease and confirmed COVID-19 infection subjected to HCQ therapy.

Results: The search process has identified 1,126 studies, of which 17 observational studies were included.No randomized controlled trials meeting the inclusion criteria were found. Eligible studies involved 229,142 autoimmune patients treated with HCQ, of which 197,118 patients were diagnosed with COVID-19. In 14 observational studies (196,965 patients), HCQ use was associated with a lower overall mortality rate by 21% in patients with autoimmune diseases and COVID-19 (RR 0.79; 95% CI: 0.64-0.97, p = 0.02). This association may reflect a potential survival benefit; however, given the observational nature of the studies included, causal inference cannot be established, and the findings should be interpreted cautiously. There was no significant difference between HCQ-treated patients and untreated patients regarding hospitalization (12 studies with 2,238 patients included), ICU admission (8 studies with 527 patients included), mechanical ventilation (8 studies with 546 patients included), sepsis (2 studies with 132 patients included), or thrombo-embolic events rates (2 studies with 195 patients included) (RR 0.92, 95% CI 0.75- 1.14; p = 0.46), (RR 1.45; 95% CI; 0.82- 2.56, p = 0.2) and (RR 1.28; 95% CI; 0.68- 2.4, p = 0.44), (RR 1.44; 95% CI; 0.57 - 3.65, p = 0.44), (RR 0.89; 95% CI; 0.16-4.97, p = 0.89), respectively. Nonetheless, the incidence of Acute Kidney Injury (AKI) in 2 studies (136 patients) was higher in HCQ-treated groups compared to the untreated groups (RR 2.31; 95% CI; 1.29-4.12, p = 0.0047).

Conclusion: HCQ was associated with a significantly lower overall mortality rate in patients with autoimmune diseases and COVID-19; this association is consistent with its known immunomodulatory properties. On the other hand, it does not prevent COVID-19-related complications and could be associated with an increased risk for developing AKI. However, given the observational nature of all included studies, causal inference cannot be established. Future research is needed to confirm these observed survival benefits and to establish clear safety parameters regarding renal toxicity.

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients.

Materials and methods: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality.

Results: A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07 mg/dL; 95% CI, -17.92 to -14.21; 14 randomized controlled trials [RCTs], 10,510 patients), total cholesterol (MD, -25.25 mg/dL; 95% CI, -29.70 to -20.81; 10 RCTs, 5,538 patients), triglycerides (MD, -19.70 mg/dL; 95% CI, -30.78 to -8.61; 9 RCTs, 4,616 patients), but also decreased HDL-C (MD, -4.91 mg/dL; 95% CI, -6.80 to -3.02; 9 RCTs, 5,132 patients). Desidustat significantly reduced LDL-C and total cholesterol, but showed no significant effects on triglycerides or HDL-C, whereas molidustat showed no significant lipid-lowering effects. Overall, treatment with HIF-PHIs was not associated with significant differences in cardiovascular death (RR, 1.00; 95% CI, 0.84 to 1.18; 10 RCTs, 9,371 patients), myocardial infarction (RR, 1.12; 95% CI, 0.90 to 1.38; 15 RCTs, 11,265 patients), stroke (RR, 1.18; 95% CI, 0.86 to 1.61; 14 RCTs, 11,136 patients), or all-cause mortality (RR, 1.06; 95% CI, 0.96 to 1.17; 19 RCTs, 11,903 patients), compared with ESAs or placebo.

Conclusion: Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo.

Background: Chronic low back pain (CLBP) is a leading cause of pain and disability worldwide. Most cases are nonspecific, lacking a clear pathological cause, and management remains challenging. Botulinum toxin type A (BoNT-A), a neurotoxin that blocks acetylcholine release and reduces muscle hyperactivity, has been studied in CLBP with inconsistent results. This meta-analysis aimed to determine the efficacy of BoNT-A compared with placebo or saline in the management of nonspecific CLBP.

Methods: A comprehensive search of PubMed, Embase, Cochrane Library, and the WHO ICTRP databases was conducted for randomized controlled trials (RCTs) involving adults with nonspecific CLBP who received BoNT-A or placebo injections and were registered in PROSPERO (CRD42024559735). The primary outcome was pain response, defined as a ≥ 50% reduction in VAS score, while the secondary outcome was functional improvement. A random-effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI).

Results: Five eligible RCTs involving 177 participants were analyzed. BoNT-A improved pain response compared with placebo [RR = 2.09, 95% CI: 1.11-3.95; p = 0.02; I² = 62%]. Functional outcomes also favored BoNT-A [RR = 2.25, 95% CI: 1.09-4.67; p = 0.03; I² = 69%]. Sensitivity analyses confirmed robustness. Exploratory meta-regression suggested a possible decrease in pain effect with longer follow-up, while functional outcomes showed no significant association; dose was not a significant moderator. Risk of bias was low in one trial, some concerns in three, and high in one. Certainty of evidence was low for both outcomes.

Conclusion: BoNT-A may improve pain and functional outcomes in nonspecific CLBP, although the certainty of evidence is low. Exploratory analyses suggested a possible decline in pain benefit over time, and safety data are limited. Larger, high-quality RCTs are needed to confirm these findings.

Purpose: This research sought to systematically evaluate the effects of pentoxifylline on renal function, anemia parameters, inflammatory status, and safety among individuals with chronic kidney disease (CKD).

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to April 9, 2026 for RCTs of pentoxifylline in CKD. Two reviewers independently performed study selection, data extraction, and quality assessment. Meta-analysis was conducted using Stata 15; continuous outcomes were pooled as MD or SMD with 95% CIs. Heterogeneity was evaluated using the I² statistic.

Results: In total, 19 studies involving 1166 patients were included. Meta-analysis showed that, compared to the control group, pentoxifylline significantly increased the estimated glomerular filtration rate (7 studies, N = 547, MD = 4.59 mL/min/1.73 m², 95% CI: 2.57-6.61) and reduced the urinary albumin excretion rate (6 studies, N = 494, SMD = -0.57, 95% CI: -1.01--0.12), C-reactive protein (10 studies, N = 594, SMD = -0.70, 95% CI: -1.08--0.31), and tumor necrosis factor-α levels (5 studies, N = 246, SMD = -0.68, 95% CI: -1.19--0.18). Regarding anemia and nutritional indicators, pentoxifylline increased hemoglobin levels (9 studies, N = 424, SMD = 0.51, 95% CI: 0.08-0.94) and potentially improved serum albumin levels (7 studies, N = 355, MD = 0.19 g/dl ,95% CI: 0.00-0.38). Nevertheless, the effects of pentoxifylline on serum ferritin, transferrin saturation, and urinary albumin-to-creatinine ratio were not significant. Regarding safety, the main adverse events included gastrointestinal symptoms, and overall tolerability appeared promising.

Conclusion: In patients with CKD, pentoxifylline safely improves renal function and reduces inflammation and anemia, with its efficacy potentially linked to the dosage and duration of treatment.

Background: In patients with reduced renal function, drug monographs recommend reduced doses of oral beta-lactams. However, dose reductions could result in suboptimal pharmacokinetic-pharmacodynamic target attainment, compromising efficacy. This study evaluated the safety of full doses of oral beta-lactams in patients with reduced renal function by assessing the incidence of neurotoxic symptoms.

Methods: This single-site, retrospective cohort study included patients with renal insufficiency prescribed full dose or renally adjusted doses of oral beta-lactams. Neurotoxicity symptoms were graded via chart review using the Naranjo Adverse Drug Reaction Probability Scale. The primary outcome was incidence of 'probable' or 'definite' beta-lactam related neurotoxicity. Multivariate logistic regression was used to adjust for differences in baseline characteristics.

Results: The cohort included 987 patients with renal insufficiency receiving 1001 full-dose courses and 122 renally adjusted dose courses. The rate of 'probable' or 'definite' neurotoxicity was 0.1% (1/1001) in the full dose group and 0.8% (1/122) in the renally adjusted group (p = 0.08). There was no difference between groups when stratified by early or late stage renal insufficiency. After adjustment for differences in baseline characteristics, receiving full dose oral beta-lactams was not associated with an increased odds of 'possible', 'probable' or 'definite' neurotoxicity as the aOR was less than 1 [aOR = 0.52, 95% CI 0.30-0.89, p = 0.02].

Conclusion: There was no increase in 'probable' or 'definite' neurotoxicities detected among patients with renal insufficiency receiving full dose as compared to renally adjusted doses of oral beta-lactams, suggesting that using full doses are a safe way to optimize the pharmacokinetic-pharmacodynamic parameters of these drugs.

Purpose: Drug supply shortages are a recurring issue in developed countries, with consequences for patients even before the COVID-19 pandemic. Questions arise regarding the effectiveness and tolerability of alternative treatments chosen by physicians due to these shortages.

Methods: To answer these questions, a survey for practicing physicians was distributed to medical associations in Germany and Austria and conducted from November 2022 to January 2024. 895 physicians responded to the survey. The survey targeted 20 drugs with known supply shortages, namely amoxicillin, amoxicillin/clavulanic acid, penicillin V (phenoxymethylpenicillin), cefuroxime, cefaclor, erythromycin, cotrimoxazole, ibuprofen, paracetamol, urapidil, metoprolol, amlodipine, candesartan, tamoxifen, methotrexate, fluoxetine, lorazepam, human insulin, salbutamol and prednisolone.

Results: Physicians most frequently chose a different antibacterial drug (> 60% of the physicians), while for analgesics, they more often used a different dosage form of the same drug (> 33%). For antihypertensive drugs, physicians more often chose a different dosage of the same drug. In many cases, alternative antibiotics were chosen that carried a greater risk of antimicrobial resistance than the antibiotic originally intended. The treatment success for replacing antibacterials and analgesics with a different drug was rated with 4-5 on a predefined scale of 1 (very poor) to 6 (very good) in comparison to the original drug. Using the same drug in a different dosage/dosage form was also around 4-5/6 effective.

Conclusions: Supply shortages can foster antimicrobial resistance through the use of antibacterials with a higher potential for resistance. The success of alternative treatments was not always considered to be very good in comparison to the original medication.

BACKGROUND: We aim to evaluate the impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). METHODS: We conducted a PRISMA-guided systematic review and meta-analysis of studies comparing SGLT2 inhibitor therapy with standard care in adults undergoing TAVI. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception to November 2025. Outcomes included all-cause mortality, heart failure (HF) hospitalization, myocardial infarction (MI), cardiac death, stroke, pacemaker implantation, acute kidney injury (AKI), and bleeding events. Effect sizes were pooled using random-effects models, while time-to-event data were reconstructed for survival analyses. RESULTS: Four studies comprising 12,374 patients were included. SGLT2 inhibitor therapy significantly reduced all-cause mortality (RR 0.62, 95% CI 0.49–0.78), HF hospitalization (RR 0.67, 95% CI 0.50–0.91), MI (RR 0.83, 95% CI 0.73–0.93), and bleeding events (RR 0.81, 95% CI 0.72–0.90). Effects on cardiac death, stroke, pacemaker implantation, and AKI were not statistically significant (P > 0.05). CONCLUSION: SGLT2 inhibitor therapy in patients undergoing TAVI was associated with reductions in all-cause mortality, HF hospitalization, and MI. However, these findings are based on a limited and heterogeneous evidence base, largely derived from observational studies, and should be interpreted with caution. The results should not be considered definitive or generalizable to all TAVI populations. Further adequately powered randomized trials are required.

PURPOSE: Certain women with heart disease require lifelong antithrombotic therapy. However, the impact of such therapy during pregnancy on maternal and neonatal outcomes remains unclear. This study aimed to investigate the prescription patterns and clinical outcomes associated with antithrombotic therapy in pregnant women with heart disease. METHODS: Using a Japanese administrative claims database, we identified pregnant women diagnosed with valvular heart disease or complex congenital heart disease between January 2008 and July 2023. In this retrospective observational study, we compared maternal clinical outcomes between women who were prescribed antithrombotic drugs during pregnancy and those who were not. For infants who could be linked to their mothers in the database, neonatal outcomes were also assessed. RESULTS: A total of 550 pregnant women with a history of heart disease were identified, of whom 90 (16.4%) received antithrombotic therapy during pregnancy. Women who received antithrombotic therapy had a higher proportion of cesarean delivery (90.0% vs. 49.8%, p < 0.001). Intensive care unit (ICU) admission rate was significantly higher in this group (24.4% vs. 10.5%, p < 0.001), as was critical obstetric bleeding (13.3% vs. 1.7%, p = 0.009). No in-hospital maternal deaths or fatal arrhythmias were observed. Among the neonates associated with their mothers, a total of 238 were identified. Admission to a neonatal ICU was significantly more frequent among infants born to women who received antithrombotic therapy (35.7% vs. 13.3%, p = 0.001). CONCLUSION: Although careful maternal and neonatal management is necessary, no in-hospital maternal deaths or severe cardiovascular events were observed among women prescribed antithrombotic therapy. This study provides valuable evidence to inform clinical decision-making in pregnant women with valvular heart disease requiring antithrombotic therapy in Japan.

Purpose: To develop and validate an age-stratified nomogram for predicting the risk of voriconazole (VRC) trough concentrations exceeding the safety threshold in pediatric patients with hematologic malignancies (HM).

Methods: We retrospectively enrolled pediatric patients with HM who received VRC treatment and underwent therapeutic drug monitoring (TDM) in our hospital, stratifying them by age and randomly assigning them to the training and test cohorts at a ratio of 6:4 and in each stratum. We screened the variables by Least Absolute Shrinkage and Selection Operator (LASSO) regression and established age-stratified prediction models using multivariate logistic regression (Models 1 and 2: ≥ and < 11 years, respectively). We evaluated model performance using the area under the receiver operating characteristic curve (AUC) and assessed the clinical net benefit by decision curve analysis.

Results: LASSO regression identified C-reactive protein, albumin, and neutropenia as well as blood urea nitrogen and direct bilirubin as independent VRC supratherapeutic concentration-influencing factors in children ≥ and < 11 years, respectively. In the test cohort, Model 1 and 2 AUCs were 0.835 and 0.814, respectively. At a high sensitivity threshold (≥ 95%), the models yielded specificities of 43.75% and 29.76%, which could reduce TDM frequency by 33.70% and 23.41%, respectively. Decision curve analysis showed both models yielded greater clinical net benefit than the "treat-all" or "treat-none" strategies.

Conclusions: The developed age-stratified prediction model could effectively identify pediatric patients with HM at high risk of VRC over-exposure, demonstrating good discrimination and clinical utility, potentially facilitating early risk warning.