European Journal Of Clinical Pharmacology[JOURNAL]
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200 papers
The Effect of the combination therapy of statin and dapagliflozin, a selective inhibitor of sodium_glucose Co-transporter type 2, in the treatment of Ischemic heart disease with heart failure: A randomized controlled trial.
Abdelkader AM, Osama H, Hassan ES … +5 more , Alsfouk BA, Elmasry TA, Elkhashab K, Hussein RRS, Kamal M
Eur J Clin Pharmacol · 2026 May · PMID 42133048 · Full text
PURPOSE: Gliflozins (SGLT2 inhibitors) and statins are key treatments commonly used in patients with ischemic heart failure. Although both are well known for diminishing cardiovascular risk and heart failure-related mort...
PURPOSE: Gliflozins (SGLT2 inhibitors) and statins are key treatments commonly used in patients with ischemic heart failure. Although both are well known for diminishing cardiovascular risk and heart failure-related mortality, the possible synergistic benefits of using them together have not been thoroughly investigated. This study aimed to correlate serum levels of Statins and SGLT2i in addition to estimate the ejection fraction and selected laboratory parameters to indicate the synergistic effect of their combination in ischemic heart disease patients. METHODS: In this prospective, randomized, controlled trial, 81participating patients with ischemic heart disease at department of cardiology, Fayoum University, were randomly enrolled into three groups: SGLT2i group (GPI) (n = 26) who took Dapagliflozin (10 mg) daily, Statin group (GPII) (n = 34) who administrated Atorvastatin (40 mg) or Rosuvastatin (40 mg) daily and Combination group (GPIII) (n = 21) who took both Statin and Dapagliflozin. They had been on treatment for three months before blood sampling. The trough plasma concentrations of the included patients were assessed by ultra-performance liquid chromatography (UPLC). Ejection fraction was assessed by echocardiography, laboratory tests were performed, and data were analyzed with SPSS v22 (p < 0.05). RESULTS: Group: III showed no adverse effects, maintained stable drug levels as the mean was 7.3 ng/ml and SD was 4.4 ng/ml (p-value 0.66), demonstrated improved ejection fraction, lipid profiles and additional metabolic benefits from SGLT2i. CONCLUSION: Dapagliflozin-statin combination therapy appears potentially beneficial for heart disease patients without affecting drug levels, though larger studies are needed to confirm.
Healthcare professionals' perspectives on medication adherence-supporting tools: a cross‑sectional survey in Italy.
Donati M, Lunghi C, Grillini G … +10 more , Domenicali M, Lunardelli ML, Pasini V, Milandri S, Mussoni M, Pieraccini F, Sangiorgi E, Raschi E, Colonnello V, Poluzzi E
Eur J Clin Pharmacol · 2026 May · PMID 42128955 · Full text
PURPOSE: Medication adherence is essential for treatment effectiveness, yet the uptake of adherence-supporting tools in routine care remains suboptimal. This study assessed Italian healthcare professionals' knowledge, pe...
PURPOSE: Medication adherence is essential for treatment effectiveness, yet the uptake of adherence-supporting tools in routine care remains suboptimal. This study assessed Italian healthcare professionals' knowledge, perceived utility, and willingness to recommend medication adherence tools, and explored perceived barriers to their adoption. METHODS: A questionnaire targeting healthcare professionals working in inpatient or outpatient settings across Italy was developed and validated by a panel of seven experts. It was anonymously distributed online between October and December 2023 to physicians, pharmacists, and nurses. The survey included open-ended and Likert-scale questions investigating use, perceived usefulness, barriers, and future willingness to recommend specific medication adherence tools. Data were analyzed using descriptive statistics, and differences by professional category were evaluated using Chi-square or Fisher's exact tests. Open-ended responses were analyzed through a multi-step conventional content analysis independently conducted by two researchers. RESULTS: A total of 660 healthcare professionals participated, including pharmacists (35%), nurses (26%), general practitioners (22%), geriatricians or internists (8.6%), and other medical doctors (8.5%). Overall, knowledge and recommendation regarding medication adherence tools were limited, with awareness ranging from 40.0% to 94.7% depending on the tool. Traditional tools such as pillboxes and paper diaries were more frequently used (42.1% and 26.3%, respectively) and were perceived as useful (26.7% and 22.3%). In contrast, digital tools (e.g., mobile apps, SMS reminders, electronic pillboxes) were rarely recommended and often described as unfamiliar. Patient-related barriers emerged as the most commonly reported obstacles for both traditional and digital tools. CONCLUSIONS: Italian healthcare professionals show limited familiarity with and use of medication adherence tools, particularly digital solutions. Targeted training and system-level strategies are needed to increase awareness, address perceived barriers, and promote the integration of effective adherence-supporting tools into routine care.
Comparison of loop diuretics for chronic heart failure: a systematic review and meta-analysis.
Taleghani S, Sørensen CC, Lukoschewitz JD … +9 more , Taraldsen IA, Tonning S, El-Sheikh M, Wisborg FD, Vishram-Nielsen J, Frydland M, Jakobsen JC, Hove JD, Grand J
Eur J Clin Pharmacol · 2026 May · PMID 42115365 · Publisher ↗
BACKGROUND: Loop diuretics relieve congestion in chronic heart failure (CHF). We systematically reviewed randomised clinical trials (RCTs) evaluating their effects. METHODS: A systematic search was conducted across major...
BACKGROUND: Loop diuretics relieve congestion in chronic heart failure (CHF). We systematically reviewed randomised clinical trials (RCTs) evaluating their effects. METHODS: A systematic search was conducted across major databases. We included RCTs that compared a loop diuretic to another loop diuretic, placebo, or "no intervention". The primary outcome was all-cause mortality, and secondary outcomes were all-cause hospitalisation, serious adverse events (SAEs), and change in body weight (kg). RESULTS: This review included 23 RCTs that enrolled 4,902 patients. Treatment with alternative loop diuretics (torsemide, azosemide and piretanide) compared with furosemide did not reduce all-cause mortality (risk ratio 1.00, 95% CI 0.89, 1.12); I = 0%; p = 0.95), nor did it reduce all-cause hospitalisations (risk ratio 0.99, 95% CI 0.84, 1.17); I = 53,46%, p = 0.92). In a pooled analysis of alternative loop diuretics (including torsemide and piretanide) the risk of SAEs was higher compared to furosemide (risk ratio 1.32, 95% CI 1.03, 1.68); I = 0%), although this finding was based on a limited number of trials with inconsistent definitions and should therefore be interpreted cautiously. The pooled meta-analysis of change in body weight did not show a difference between loop diuretics (mean difference 0.00 kg, 95% CI -1.19, 1.20; I = 92.43), indicating substantial heterogeneity. Azosemide resulted in a significant weight loss reduction compared to furosemide (mean difference - 1.00 kg, 95% CI -1.42, -0.58) based on a single small study. CONCLUSIONS: The choice of loop diuretic did not seem to influence the risk of mortality. In a pooled analysis of torsemide and piretanide, the risk of SAEs was higher when compared to furosemide, but the certainty of this finding is limited. Azosemide was associated with weight loss compared to furosemide in one small trial.
Short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval: a target trial emulation.
Chen X, Liu Y, Wei W … +6 more , Xia X, Wu X, Lu X, Hu G, Lu S, Shen Y
Eur J Clin Pharmacol · 2026 May · PMID 42104119 · Full text
OBJECTIVE: To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, an...
OBJECTIVE: To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, and to assess whether target trial emulation (TTE) can replicate RCT findings for a pharmacological safety outcome at substantially greater scale. DESIGN: Retrospective cohort study emulating a target trial, reported according to the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) guideline. SETTING: Single tertiary A teaching hospital in China, March 2012 to September 2024. PARTICIPANTS: Of 619,216 cardiology hospitalizations, 165,460 new statin users with suspected coronary artery disease met all eligibility criteria. After 1:1 propensity score matching, 98,860 patients (49,430 per group) constituted the analytic cohort. All standardized mean differences were below 0.013 after matching. MAIN OUTCOME MEASURES: The primary outcome was the change in Fridericia-corrected QT interval (ΔQTcF) from baseline to first follow-up electrocardiogram (24-72 h). Secondary outcomes included newly emerged QTc prolongation, any QTc increase, clinically significant increase (> 30 ms), severe QTc prolongation, and a composite cardiac safety endpoint. Both intention-to-treat and per-protocol effects were estimated. RESULTS: The mean ΔQTcF in the rosuvastatin group was + 7.71 ms (SD 20.41) versus + 0.31 ms (SD 22.30) in the atorvastatin group, yielding a between-group difference of 7.40 ms (95% CI 7.13 to 7.67; P < 0.001). Newly emerged QTc prolongation occurred in 14.7% versus 10.5% (risk ratio 1.40, 95% CI 1.35 to 1.45). The composite cardiac safety endpoint did not differ (0.4% versus 0.5%; P = 0.24). Results were consistent across eight subgroups and six sensitivity analyses. The TTE estimate was concordant with the published RCT finding of 7.40 ms (heterogeneity P = 1.00), with a 14-fold narrower confidence interval. The negative control outcome analysis showed no residual bias. CONCLUSIONS: Rosuvastatin was associated with a 7.40 ms greater short-term QTcF prolongation than atorvastatin in a cohort 212 times larger than the emulated RCT, without excess clinical cardiac events over a mean follow-up of 48 h. Target trial emulation successfully replicated the RCT finding for a short-term drug safety outcome, demonstrating the framework's value for pharmacovigilance research using routine clinical data.
The impact of denosumab and calcitriol on asthma risk and lung function: a drug target mendelian randomization study.
Jiang Z, Zhang M, Wu M … +6 more , Deng S, Zhang B, Lei T, Du W, Diao W, Zheng X
Eur J Clin Pharmacol · 2026 May · PMID 42104117 · Publisher ↗
BACKGROUND: Osteoporosis and asthma are prevalent chronic conditions that significantly impact public health. Inflammatory cell merging, leading to reduced bone density, increases the risk of fractures, while asthma is a...
BACKGROUND: Osteoporosis and asthma are prevalent chronic conditions that significantly impact public health. Inflammatory cell merging, leading to reduced bone density, increases the risk of fractures, while asthma is a chronic respiratory disease characterized by airway inflammation and bronchoconstriction. More and more emerging research suggests a potential connection through shared pathways and biological mechanisms. In this study, we aim to investigate the causal effect of anti-osteoporosis drug treatment on chronic disease asthma through the Mendelian randomization (MR) analysis method. METHOD: In our study, we employed a two-stage study design, utilizing observational data from the National Health and Nutrition Examination Survey (NHANES) and summary statistics data from genome-wide association studies (GWAS) with a large sample of European adults. Section-cross research was performed using NHANES datasets and analysis of the risk of asthma with bone mineral density (BMD) through a risk proportion regression model. After that, a two-sample MR analysis was performed to investigate the causal effect of anti-osteoporosis drug therapy on asthma. Finally, sensitivity analysis was conducted to evaluate the stability of the results. RESULTS: Our study revealed a non-linear association between femur BMD and asthma risk, with a critical inflection point at a BMD value of 1.114 g/cm. MR analysis indicated that denosumab did not exert a causal effect on asthma risk (OR = 1.008, 95% CI: 0.994-1.022, P = 0.285) but was associated with improved lung function (β = 0.085, 95% CI: 0.006-0.164, P = 0.035). Conversely, calcitriol exhibited a protective effect against both asthma (OR = 0.931, 95% CI: 0.894-0.969, P < 0.001) and lung function decline (β = 0.294, 95% CI: 0.062-0.525, P = 0.013). These findings suggest a pleiotropic role for these anti-osteoporosis drugs in respiratory health. CONCLUSION: This study provides novel insights into the complex relationships between osteoporosis treatments, bone health, and asthma risk. The use of MR analysis enhances the reliability of our findings and highlights the potential benefits of osteoporosis treatments in reducing asthma risk and improving lung function. These results call for further research and may have implications for developing integrated treatment approaches for individuals managing osteoporosis and asthma.
The impact of gene polymorphisms on the response of methotrexate-based treatments.
Esperón P, Vital M, Giletti A
Eur J Clin Pharmacol · 2026 May · PMID 42104114 · Publisher ↗
PURPOSE: Methotrexate (MTX) is a long-standing drug used to treat leukemia (at high doses to inhibit DNA/RNA synthesis) and rheumatoid arthritis (at low doses for anti-inflammatory effects). Its characteristic narrow the...
PURPOSE: Methotrexate (MTX) is a long-standing drug used to treat leukemia (at high doses to inhibit DNA/RNA synthesis) and rheumatoid arthritis (at low doses for anti-inflammatory effects). Its characteristic narrow therapeutic range, in terms of efficacy and safety associated with MTX, are important factors to consider when deciding whether to prescribe it. A major challenge in its use is interindividual variability which is largely attributed to germline genetic polymorphisms in genes encoding proteins that control the pharmacokinetics or pharmacodynamics of MTX. METHODS: This study updates a previous 2018 review using a systematic literature search in PubMed/MEDLINE, Scopus, and SciELO. The search, conducted according to the PRISMA protocol, employed predefined keywords to identify studies published up to June 2025. RESULTS: This systematic review identified that, to date, only a few genetic polymorphisms influence clinical decision-making. Specifically, the MTHFR 677T allele and the MTHFR 677T-1298 A haplotype (rs1801133- rs1801131) have been associated with toxicity in both adults and children. Furthermore, the 677T-1298 A haplotype has been linked with reduced event-free survival in Caucasian patients with either adult RA or pediatric ALL. Regarding other markers, the TYMS rs34743033 3R allele has been implicated with reduced efficacy in adult patients receiving low-dose MTX, while the FPGS rs1544105 T allele has shown an association with diverse toxicities in ALL pediatric patients. CONCLUSION: Although considerable research has been conducted and numerous results have been obtained, the available evidence remains predominantly of moderate quality. Consequently, current guidelines from CPIC and the DPWG do not recommend routine MTX dose adjustments based solely on single gene variants. It is, therefore, imperative to develop and validate multifactorial risk prediction tools that integrate a range of other clinical factors. Accordingly, the establishment of a comprehensive pharmacogenetics-guided dosing guideline for MTX remains an elusive goal.
Physicians' gender and specialty in relation to adverse drug reaction reporting in Sweden.
Nordvall LM, Rolander B, Larsson M … +3 more , Melin L, Hägg S, Kling A
Eur J Clin Pharmacol · 2026 May · PMID 42098474 · Full text
PURPOSE: To evaluate the possible influence of gender and specialty on adverse drug reaction (ADR) reporting among physicians before and after the COVID-19 pandemic. METHODS: This retrospective nationwide register study...
PURPOSE: To evaluate the possible influence of gender and specialty on adverse drug reaction (ADR) reporting among physicians before and after the COVID-19 pandemic. METHODS: This retrospective nationwide register study analysed all ADR reports submitted by physicians to the Swedish Medical Products Agency during 2017 and 2023 (n = 4079 and 3740, respectively). The reporting rates were calculated and stratified by gender and specialty. RESULTS: The highest reporting rate among physicians was observed in medical specialties, followed by primary care and psychiatry (27, 10, and 12, reports/100 physicians in 2017; 18, 15, and 9 in 2023). The lowest reporting rates were observed for surgical and hospital service specialties (8 and 1 in 2017; 6 and 1 in 2023). Male and female physicians reported ADRs to a similar extent and both reported more frequently on female patients. Gender concordance between physician and patient was associated with significantly higher reporting (p < 0.001 in 2017; p = 0.041 in 2023). CONCLUSION: Reporting varied across specialties, and gender concordance emerged as a previously unrecognized factor influencing ADR reporting. These findings provide new opportunities for targeted interventions to enhance physician participation in pharmacovigilance.
Association between anticholinergic and sedative medications and physical functioning: data from the Canadian longitudinal study on aging (CLSA).
Pelen K, Boissy P, Lebel K … +12 more , Mayhew A, Beauchamp MK, Griffith LE, O'Connell ME, Hilmer SN, Baroud ML, Sirois C, Moriarty F, Turcotte JP, O'Donnell LK, Nicholson K, Cossette B
Eur J Clin Pharmacol · 2026 May · PMID 42098348 · Publisher ↗
PURPOSE: The cumulative use of anticholinergic and sedative medications has been associated with lower physical function in older adults. This study aimed to identify which physical function attributes are most impacted...
PURPOSE: The cumulative use of anticholinergic and sedative medications has been associated with lower physical function in older adults. This study aimed to identify which physical function attributes are most impacted in subgroups aged 45-64 and 65-85 years. METHODS: Baseline data from 30,097 community-living Canadians in the Canadian Longitudinal Study on Aging were analysed using a cross-sectional design. Anticholinergic and sedative medications use was quantified using the Drug Burden Index (DBI). Physical functioning was measured via the timed 4-meter walk, Timed Up and Go (TUG), single leg balance, chair rise and grip strength. Physical functioning profiles were generated using latent profile analysis of the five tests. Associations between DBI scores and physical functioning were assessed through linear regression and multinomial logistic regression. RESULTS: The mean age of participants was 63.0, 50.9% were female, 18.3% had a DBI score 0 < DBI < 1 and 8.7% a DBI score ≥ 1. Adjusted regression models showed the greatest reduction in standardized scores for the TUG test among participants with DBI ≥ 1 (β: -6.05; -6.77 to - 5.33) relative to DBI = 0. Latent profile analysis indicated that the two profiles with the poorest physical functioning were associated with higher odds of exposure to 0 < DBI < 1 and DBI ≥ 1, whereas the profile reflecting the best functioning was associated with reduced odds of exposure to DBI ≥ 1. Associations of similar magnitude were observed across age strata (45-64 and 65-85 years). CONCLUSION: Cumulative anticholinergic and sedative medication burden was inversely associated with physical functioning. These findings were consistent across middle-aged and older adults.
The efficacy and safety of pentoxifylline in the treatment of chronic kidney disease: a systematic review and meta-analysis.
Xu Y, Xu F, Shen W
Eur J Clin Pharmacol · 2026 May · PMID 42091733 · Publisher ↗
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: P...
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.
Exploring the long-term hydroxychloroquine's effects on COVID-19 outcomes in patients with autoimmune diseases: a systematic review and meta-analysis.
Amal HM, Mohamed AMG, Abdel-Halim MO … +3 more , Hassan MS, Khorshid OA, Osman WA
Eur J Clin Pharmacol · 2026 May · PMID 42091717 · Publisher ↗
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 rema...
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.
The role of Spanish clinical pharmacologists in economic evaluations of health technologies.
Delgado-Espinoza CE, Antonijoan RM, Martínez-Zapata MJ
Eur J Clin Pharmacol · 2026 May · PMID 42091708 · Full text
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 provi...
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.
Efficacy of botulinum toxin type a for treating chronic low back pain: a systematic review and metanalysis.
G BK, Jain M, Meher BR … +3 more , Padhy BM, Sakale H, Kumar S
Eur J Clin Pharmacol · 2026 May · PMID 42091699 · Publisher ↗
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 (Bo...
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; I = 62%]. Functional outcomes also favored BoNT-A [RR = 2.25, 95% CI: 1.09-4.67; p = 0.03; I = 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.
Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on lipid profiles in patients with chronic kidney disease: a systematic review and meta-analysis.
Huang YH, Huang YH, Peng TR … +1 more , Wu TW
Eur J Clin Pharmacol · 2026 May · PMID 42091697 · Publisher ↗
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 systematica...
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.
Examining the risk of neurotoxicity in patients who receive unadjusted doses of oral beta-lactams in renal insufficiency: a retrospective cohort study.
Zlotnik N, Lam PW, Lo J … +4 more , Palmay L, Leis JA, Daneman N, Elligsen M
Eur J Clin Pharmacol · 2026 May · PMID 42086842 · Publisher ↗
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, co...
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.
Drug supply shortages and their perceived consequences for patients: a questionnaire survey of German and Austrian physicians.
Rotter JM, Seifert R
Eur J Clin Pharmacol · 2026 May · PMID 42062544 · Full text
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 t...
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.
Maternal and neonatal outcomes of antithrombotic therapy in pregnant women with valvular or complex congenital heart disease: a nationwide retrospective cohort study in Japan.
Yanagisawa Y, Tsuchiya M, Imai S … +2 more , Kizaki H, Hori S
Eur J Clin Pharmacol · 2026 Apr · PMID 42056467 · Publisher ↗
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 t...
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.
Therapeutic impact of SGLT2 inhibitors following transcatheter aortic valve implantation: a grade-assessed systematic review and meta-analysis.
Hamzah KA, Kurmasha YH, Al-Shammari AS … +5 more , Shweliya MA, Al-Janabi AAH, Shahzaib M, Akoum A, Sattar Y
Eur J Clin Pharmacol · 2026 Apr · PMID 42056230 · Publisher ↗
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). METHO...
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.
Age-stratified nomogram development and validation for predicting voriconazole trough concentrations above safety threshold in pediatric patients with hematologic malignancy.
An N, Han Y, Jia C … +3 more , Ding W, Liu J, Zhao Y
Eur J Clin Pharmacol · 2026 Apr · PMID 42053650 · Publisher ↗
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). MET...
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.
Revisiting disulfiram-like reactions with antibiotics: evidence, misattribution, and the need for updated clinical guidance.
Li J, Sun J, Yu J
Eur J Clin Pharmacol · 2026 Apr · PMID 42047793 · Publisher ↗
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Authors response to the comments by Muhammad Salman, Muhammad Hammad Chola and Muhammad Hasan on our paper "prescribing patterns of glucagon like peptide-1 receptor agonists in the Swedish capital region: a register-based cross-sectional study".
Fors A, Forslund T, Sundström A … +1 more , Wettermark B
Eur J Clin Pharmacol · 2026 Apr · PMID 42036553 · Publisher ↗
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