Katrine Mose, Carina Lundby, Lotte Rasmussen, Anton Pottegård
This scoping review provides an overview of tools used to assess potentially inappropriate prescribing among older adults and discusses their suitability for register-based research. We performed a systematic search using PubMed (March 2024), retrieving 5493 records. Studies were included if they evaluated potentially inappropriate medication use among older adults with a mean or median age of ≥ 65 years. Identified tools were described by characteristics, usage frequency, and applicability to register-based research by identifying required data types. A total of 419 studies were included, using 44 different tools, including multiple versions. Beers criteria and the Screening Tool of Older People's Prescriptions were most often used (50% and 19%, respectively). Ten tools were used in five or more studies, each differing in structure, particularly regarding the clinical information required. The European list of potentially inappropriate medications, the PRISCUS list, the Zhan criteria, and the Norwegian General Practice criteria do not require clinical data on medical history, symptoms, laboratory tests or other parameters, making them particularly useful for register-based research. Specific segments of other tools can also be applied effectively. To generate valid and meaningful results, the availability of required data is a crucial consideration for researchers when selecting the most appropriate tool.
{"title":"Tools for Evaluating Potentially Inappropriate Medication Use in Older Adults: A Scoping Review Assessing Suitability for Register-Based Research","authors":"Katrine Mose, Carina Lundby, Lotte Rasmussen, Anton Pottegård","doi":"10.1111/bcpt.70094","DOIUrl":"https://doi.org/10.1111/bcpt.70094","url":null,"abstract":"<p>This scoping review provides an overview of tools used to assess potentially inappropriate prescribing among older adults and discusses their suitability for register-based research. We performed a systematic search using PubMed (March 2024), retrieving 5493 records. Studies were included if they evaluated potentially inappropriate medication use among older adults with a mean or median age of ≥ 65 years. Identified tools were described by characteristics, usage frequency, and applicability to register-based research by identifying required data types. A total of 419 studies were included, using 44 different tools, including multiple versions. Beers criteria and the Screening Tool of Older People's Prescriptions were most often used (50% and 19%, respectively). Ten tools were used in five or more studies, each differing in structure, particularly regarding the clinical information required. The European list of potentially inappropriate medications, the PRISCUS list, the Zhan criteria, and the Norwegian General Practice criteria do not require clinical data on medical history, symptoms, laboratory tests or other parameters, making them particularly useful for register-based research. Specific segments of other tools can also be applied effectively. To generate valid and meaningful results, the availability of required data is a crucial consideration for researchers when selecting the most appropriate tool.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vladyslav Shapoval, Perrine Evrard, François-Xavier Sibille, María López-Toribio, Olivia Dalleur, Carole E. Aubert, Lucy Bolt, Vagioula Tsoutsi, Maria Ntafouli, Laura Fernández Maldonado, Ramon Miralles, Adam Wichniak, Katarzyna Gustavsson, Torgeir Bruun Wyller, Enrico Callegari, Jeremy M. Grimshaw, Justin Presseau, Séverine Henrard, Anne Spinewine
Although physicians are primarily responsible for Benzodiazepine Receptor Agonist (BZRA) deprescribing, nonphysician healthcare professionals (HCPs) can support deprescribing. This study explored barriers to and enablers of BZRA deprescribing among nonphysician HCPs. We surveyed 258 HCPs (63.2% nurses) working in hospital settings across six European countries using a questionnaire based on the Theoretical Domain Framework (TDF). Logistic regression assessed associations between TDF domains and both intentions to support and routine engagement in BZRA deprescribing. Major barriers (TDF items with mean < 3) were found in the goals (competing priorities), environmental context and resources (time and staff lack) and social influences (patient reluctance) domains. Five TDF domains were associated with a stronger intention to support deprescribing: social/professional role and identity (OR, 3.08; 95% CI, 1.77–5.46); beliefs about consequences (OR, 1.91; 95% CI, 1.07–3.34); memory, attention and decision processing (OR, 1.80; 95% CI, 1.16–2.82); intention to promote alternatives (OR, 1.63; 95% CI, 1.07–2.49); and reinforcement (OR, 1.57; 95% CI, 1.08–2.29). Knowledge was the only domain associated with routine BZRA deprescribing support (OR, 1.16; 95% CI, 1.06–1.27). Different categories of HCPs face similar major barriers, but barriers vary across HCP categories and countries. Context-specific, targeted interventions may enhance support for BZRA deprescribing.
{"title":"Barriers to and Enablers of Supporting Deprescribing Benzodiazepines in Older Adults: A Survey of European Nonphysician Healthcare Professionals","authors":"Vladyslav Shapoval, Perrine Evrard, François-Xavier Sibille, María López-Toribio, Olivia Dalleur, Carole E. Aubert, Lucy Bolt, Vagioula Tsoutsi, Maria Ntafouli, Laura Fernández Maldonado, Ramon Miralles, Adam Wichniak, Katarzyna Gustavsson, Torgeir Bruun Wyller, Enrico Callegari, Jeremy M. Grimshaw, Justin Presseau, Séverine Henrard, Anne Spinewine","doi":"10.1111/bcpt.70100","DOIUrl":"https://doi.org/10.1111/bcpt.70100","url":null,"abstract":"<p>Although physicians are primarily responsible for Benzodiazepine Receptor Agonist (BZRA) deprescribing, nonphysician healthcare professionals (HCPs) can support deprescribing. This study explored barriers to and enablers of BZRA deprescribing among nonphysician HCPs. We surveyed 258 HCPs (63.2% nurses) working in hospital settings across six European countries using a questionnaire based on the Theoretical Domain Framework (TDF). Logistic regression assessed associations between TDF domains and both intentions to support and routine engagement in BZRA deprescribing. Major barriers (TDF items with mean < 3) were found in the goals (competing priorities), environmental context and resources (time and staff lack) and social influences (patient reluctance) domains. Five TDF domains were associated with a stronger intention to support deprescribing: social/professional role and identity (OR, 3.08; 95% CI, 1.77–5.46); beliefs about consequences (OR, 1.91; 95% CI, 1.07–3.34); memory, attention and decision processing (OR, 1.80; 95% CI, 1.16–2.82); intention to promote alternatives (OR, 1.63; 95% CI, 1.07–2.49); and reinforcement (OR, 1.57; 95% CI, 1.08–2.29). Knowledge was the only domain associated with routine BZRA deprescribing support (OR, 1.16; 95% CI, 1.06–1.27). Different categories of HCPs face similar major barriers, but barriers vary across HCP categories and countries. Context-specific, targeted interventions may enhance support for BZRA deprescribing.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rhianna Griffiths, Steve Lim, Julian Lin, Andrew Bates, Liam Jones, Kinda Ibrahim
Background
Anticholinergic medication use is increasing, particularly among older adults due to polypharmacy and comorbidities. High anticholinergic burden is linked to adverse outcomes such as reduced mobility and increased dementia risk. Acute hospital stays may offer an opportunity to address this often-overlooked issue.
Aims
To examine the effects of deprescribing anticholinergic medications on outcomes in older hospitalised patients.
Methods
Medline, Web of Science, Cochrane Library and Embase were searched from inception to September 2024. Studies included hospital-based deprescribing or medication review interventions targeting anticholinergic burden in patients aged ≥ 65 years. Narrative synthesis followed SWiM guidelines, with quality assessment using JBI Checklists.
Results
From 2042 records, eight studies met inclusion criteria. Designs included cohort (n = 4) and pre-post quasi-experimental (n = 4), with follow-up durations of up to 3 months. All reported medication-related outcomes; four assessed acceptability, one included clinical outcomes, and none examined safety. Six studies reported reductions in anticholinergic burden scores; three showed significant decreases in the proportion of patients prescribed anticholinergics, and two noted fewer potentially inappropriate medications. Most recommended changes were implemented.
Conclusion
Deprescribing interventions in hospital appear acceptable and effective in reducing anticholinergic burden. However, evidence on clinical outcomes, costs and safety is limited. Further RCTs with longer follow-up are needed.
背景抗胆碱能药物的使用正在增加，特别是在老年人中，由于多种药物和合并症。高抗胆碱能负荷与活动能力降低和痴呆风险增加等不良后果有关。急性住院可能提供了一个机会来解决这个经常被忽视的问题。目的探讨抗胆碱能药物对老年住院患者预后的影响。方法检索Medline、Web of Science、Cochrane Library和Embase数据库，检索时间为建站至2024年9月。研究包括针对≥65岁患者抗胆碱能负担的以医院为基础的处方减少或药物回顾干预措施。叙事综合遵循SWiM指南，使用JBI检查清单进行质量评估。结果在2042份记录中，有8项研究符合纳入标准。设计包括队列（n = 4）和前后准实验（n = 4），随访时间长达3个月。所有报告的药物相关结果；四项评估可接受性，一项包括临床结果，没有一项评估安全性。六项研究报告了抗胆碱能负荷评分的降低；其中3项研究显示，服用抗胆碱能药物的患者比例显著下降，2项研究指出，潜在的不适当药物减少了。大多数建议的更改都已实现。结论减轻医院抗胆碱能负担可接受且有效。然而，关于临床结果、成本和安全性的证据有限。需要更长的随访时间进行进一步的随机对照试验。
{"title":"Deprescribing Anticholinergic Medications in Hospitalised Older Adults: A Systematic Review","authors":"Rhianna Griffiths, Steve Lim, Julian Lin, Andrew Bates, Liam Jones, Kinda Ibrahim","doi":"10.1111/bcpt.70103","DOIUrl":"https://doi.org/10.1111/bcpt.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anticholinergic medication use is increasing, particularly among older adults due to polypharmacy and comorbidities. High anticholinergic burden is linked to adverse outcomes such as reduced mobility and increased dementia risk. Acute hospital stays may offer an opportunity to address this often-overlooked issue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To examine the effects of deprescribing anticholinergic medications on outcomes in older hospitalised patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Medline, Web of Science, Cochrane Library and Embase were searched from inception to September 2024. Studies included hospital-based deprescribing or medication review interventions targeting anticholinergic burden in patients aged ≥ 65 years. Narrative synthesis followed SWiM guidelines, with quality assessment using JBI Checklists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 2042 records, eight studies met inclusion criteria. Designs included cohort (<i>n</i> = 4) and pre-post quasi-experimental (<i>n</i> = 4), with follow-up durations of up to 3 months. All reported medication-related outcomes; four assessed acceptability, one included clinical outcomes, and none examined safety. Six studies reported reductions in anticholinergic burden scores; three showed significant decreases in the proportion of patients prescribed anticholinergics, and two noted fewer potentially inappropriate medications. Most recommended changes were implemented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Deprescribing interventions in hospital appear acceptable and effective in reducing anticholinergic burden. However, evidence on clinical outcomes, costs and safety is limited. Further RCTs with longer follow-up are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongpan An, Bowen Zhang, Yuwei Ye, Xianghong Wang, Chi Zhang, Jianjun Ding, Ke Gao, Yanan Ouyang, Ruixiao Li, Yi Ying, Xiaorong Xue, Guojun Wu
Inflammatory bowel diseases (IBD) are chronic and recurrent gastrointestinal disorders affecting millions worldwide, imposing significant social and economic burdens. Safe and effective medications for IBD prevention and treatment are urgently needed. SNX10 has emerged as a potential therapeutic target, while traditional Chinese medicine (TCM) active compounds offer unique advantages in drug development due to their inherent safety and therapeutic properties. This study aimed to identify TCM compounds targeting SNX10 using molecular docking, molecular dynamics (MD) and MMGBSA binding free energy calculations. From a pool of 300 + TCM compounds, vitexin-4″-O-glucoside, scutellarin, diosmin and alpha-hederin were identified as promising candidates. Alpha-hederin exhibited the strongest binding affinity (−50.19 kJ/mol) via robust electrostatic and hydrophobic interactions, as revealed by MMGBSA, correlating with its superior efficacy in alleviating DSS-induced IBD in mice. Additionally, surface plasmon resonance (SPR) results showed that alpha-hederin can directly bind to SNX10 with a dissociation constant (Kd) of 3.02 μM. RNA-sequencing results show that alpha-hederin works by reducing inflammation and promoting gut cell proliferation. These findings not only propose novel TCM candidates for IBD management but also reinforce SNX10 as a therapeutic target and provide a scalable screening framework for TCM-based drug discovery.
炎症性肠病（IBD）是慢性和复发性胃肠道疾病，影响全球数百万人，造成重大的社会和经济负担。目前迫切需要安全有效的IBD预防和治疗药物。SNX10已成为潜在的治疗靶点，而中药活性化合物由于其固有的安全性和治疗性，在药物开发中具有独特的优势。本研究旨在通过分子对接、分子动力学（MD）和MMGBSA结合自由能计算，鉴定靶向SNX10的中药化合物。从300多个中药化合物中，牡荆素-4″- o -葡萄糖苷、黄芩苷、薯蓣皂苷和α -hederin被确定为有希望的候选化合物。MMGBSA显示，α -hederin通过强大的静电和疏水相互作用表现出最强的结合亲和力（−50.19 kJ/mol），这与其在缓解dss诱导的小鼠IBD中的优越疗效有关。此外，表面等离子体共振（SPR）结果表明，α -hederin可以直接与SNX10结合，解离常数（Kd）为3.02 μM。rna测序结果表明，α -hederin通过减少炎症和促进肠道细胞增殖而起作用。这些发现不仅为IBD的治疗提供了新的中药候选药物，而且强化了SNX10作为治疗靶点的作用，并为基于中药的药物发现提供了可扩展的筛选框架。
{"title":"Computer-Assisted Screening of Active Compounds in Traditional Chinese Medicine Targeting SNX10 as a Promising Treatment for Inflammatory Bowel Diseases","authors":"Yongpan An, Bowen Zhang, Yuwei Ye, Xianghong Wang, Chi Zhang, Jianjun Ding, Ke Gao, Yanan Ouyang, Ruixiao Li, Yi Ying, Xiaorong Xue, Guojun Wu","doi":"10.1111/bcpt.70098","DOIUrl":"https://doi.org/10.1111/bcpt.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammatory bowel diseases (IBD) are chronic and recurrent gastrointestinal disorders affecting millions worldwide, imposing significant social and economic burdens. Safe and effective medications for IBD prevention and treatment are urgently needed. SNX10 has emerged as a potential therapeutic target, while traditional Chinese medicine (TCM) active compounds offer unique advantages in drug development due to their inherent safety and therapeutic properties. This study aimed to identify TCM compounds targeting SNX10 using molecular docking, molecular dynamics (MD) and MMGBSA binding free energy calculations. From a pool of 300 + TCM compounds, vitexin-4″-O-glucoside, scutellarin, diosmin and alpha-hederin were identified as promising candidates. Alpha-hederin exhibited the strongest binding affinity (−50.19 kJ/mol) via robust electrostatic and hydrophobic interactions, as revealed by MMGBSA, correlating with its superior efficacy in alleviating DSS-induced IBD in mice. Additionally, surface plasmon resonance (SPR) results showed that alpha-hederin can directly bind to SNX10 with a dissociation constant (Kd) of 3.02 μM. RNA-sequencing results show that alpha-hederin works by reducing inflammation and promoting gut cell proliferation. These findings not only propose novel TCM candidates for IBD management but also reinforce SNX10 as a therapeutic target and provide a scalable screening framework for TCM-based drug discovery.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyu Zhang, Yupeng Zhang, Xinghang Tang, Li Chen
Objective
This study aimed to compare adverse event (AE) profiles between Avastin and bevacizumab biosimilars to support clinical decision-making, given the limited availability of real-world data.
Methods
A disproportionality analysis was conducted using the FDA Adverse Event Reporting System (FAERS) to identify and compare AE signals. Signals were evaluated at the system organ classes (SOCs) and preferred term (PT) levels, focusing on the Top 20 PTs by report number, key SOCs and outcomes.
Results
Injury, poisoning and procedural complications and general disorders and administration site conditions were the most frequent SOCs in both groups. Common label-listed AEs, including hypertension, proteinuria and thrombocytopenia, were frequently reported. Shared risks also included gastrointestinal perforation/ulceration and thromboembolism. Avastin was more associated with red blood cell disorders and ureteric disorders and bladder and bladder-neck disorders, while biosimilars were linked to a broader range of high-level group terms in gastrointestinal disorders and generated more renal and urinary signals.
Conclusion
Hypertension, proteinuria, thrombocytopenia, gastrointestinal perforation and thromboembolism remain key concerns. Clinicians should monitor renal and urinary function when administering Avastin. Immune-induced renal disorders associated with biosimilars highlight the importance of assessing the treatment rationale in patients with chronic kidney disease, autoimmune disorders or other comorbid conditions.
{"title":"Comparative Safety Analysis of Avastin and Bevacizumab Biosimilars Based on Food and Drug Administration Adverse Event Reporting System","authors":"Xiaoyu Zhang, Yupeng Zhang, Xinghang Tang, Li Chen","doi":"10.1111/bcpt.70099","DOIUrl":"https://doi.org/10.1111/bcpt.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to compare adverse event (AE) profiles between Avastin and bevacizumab biosimilars to support clinical decision-making, given the limited availability of real-world data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A disproportionality analysis was conducted using the FDA Adverse Event Reporting System (FAERS) to identify and compare AE signals. Signals were evaluated at the system organ classes (SOCs) and preferred term (PT) levels, focusing on the Top 20 PTs by report number, key SOCs and outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Injury, poisoning and procedural complications and general disorders and administration site conditions were the most frequent SOCs in both groups. Common label-listed AEs, including hypertension, proteinuria and thrombocytopenia, were frequently reported. Shared risks also included gastrointestinal perforation/ulceration and thromboembolism. Avastin was more associated with red blood cell disorders and ureteric disorders and bladder and bladder-neck disorders, while biosimilars were linked to a broader range of high-level group terms in gastrointestinal disorders and generated more renal and urinary signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hypertension, proteinuria, thrombocytopenia, gastrointestinal perforation and thromboembolism remain key concerns. Clinicians should monitor renal and urinary function when administering Avastin. Immune-induced renal disorders associated with biosimilars highlight the importance of assessing the treatment rationale in patients with chronic kidney disease, autoimmune disorders or other comorbid conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144909940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute kidney injury (AKI) is a serious complication of cisplatin chemotherapy, with limited treatment options. In this study, we investigated the protective effects of wine-processed Polygonatum sibiricum (WP. P. sibiricum) against cisplatin-induced acute kidney injury (DDP-AKI) using an integrated approach combining UPLC-Q-TOF-MS/MS analysis, network pharmacology, molecular docking and in vivo/vitro experimental validation. The WP. P. sibiricum extract demonstrated dose-dependent renal protection in mice with DDP-AKI, significantly attenuating weight loss (p < 0.05), improving renal function (reduced serum BUN by 29.2%–38.9% and CRE by 8.0%–36.7%), reducing tubular necrosis and biomarkers (NGAL decreased 49.2%–86.6%, p < 0.01), while showing no hepatotoxicity. In addition, WP. P. sibiricum elevated SOD activity by 15.5%–28.5% and reduced MDA levels by 13.5%–26.9% (p < 0.01). UPLC-Q-TOF-MS/MS analysis elucidated eight bioactive components (e.g., flavonoids and glycosides). Network pharmacology revealed 132 targets shared by WP. P. sibiricum and DDP-AKI, such as mTOR, STAT3 and PPAR. Molecular docking confirmed strong binding (≤ −6.0 kcal·mol−1) between core components and targets. Mechanistically, WP. P. sibiricum activated the mTOR pathway (p < 0.01) and suppressed apoptosis (p < 0.01), with effects comparable or superior to those of NAC. This study is the first to validate the nephroprotective effect of WP. P. sibiricum, linking its multi-target effects (mTOR/ROS/apoptosis) to enhanced phytochemical potency. These findings support WP. P. sibiricum as a clinically translatable adjuvant for DDP-AKI.
{"title":"Multi-Target Renal Protection of Wine-Processed Polygonatum sibiricum Against Cisplatin-Induced Nephrotoxicity: Integrated Phytochemistry, Network Pharmacology and Experimental Validation","authors":"Yu Jiang, Wei Qiao, Kaili Guo, Hanbin Luo, Xin Liu, Jiping Liu, Hao Wei, Bin Wang, Xiao Chen, Hong Ren, Xingmei Zhu","doi":"10.1111/bcpt.70092","DOIUrl":"https://doi.org/10.1111/bcpt.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute kidney injury (AKI) is a serious complication of cisplatin chemotherapy, with limited treatment options. In this study, we investigated the protective effects of wine-processed <i>Polygonatum sibiricum</i> (WP. <i>P. sibiricum</i>) against cisplatin-induced acute kidney injury (DDP-AKI) using an integrated approach combining UPLC-Q-TOF-MS/MS analysis, network pharmacology, molecular docking and in vivo/vitro experimental validation. The WP. <i>P</i>. <i>sibiricum</i> extract demonstrated dose-dependent renal protection in mice with DDP-AKI, significantly attenuating weight loss (<i>p <</i> 0.05), improving renal function (reduced serum BUN by 29.2%–38.9% and CRE by 8.0%–36.7%), reducing tubular necrosis and biomarkers (NGAL decreased 49.2%–86.6%, <i>p <</i> 0.01), while showing no hepatotoxicity. In addition, WP. <i>P</i>. <i>sibiricum</i> elevated SOD activity by 15.5%–28.5% and reduced MDA levels by 13.5%–26.9% (<i>p <</i> 0.01). UPLC-Q-TOF-MS/MS analysis elucidated eight bioactive components (e.g., flavonoids and glycosides). Network pharmacology revealed 132 targets shared by WP. <i>P</i>. <i>sibiricum</i> and DDP-AKI, such as mTOR, STAT3 and PPAR. Molecular docking confirmed strong binding (≤ −6.0 kcal·mol<sup>−1</sup>) between core components and targets. Mechanistically, WP. <i>P</i>. <i>sibiricum</i> activated the mTOR pathway (<i>p <</i> 0.01) and suppressed apoptosis (<i>p <</i> 0.01), with effects comparable or superior to those of NAC. This study is the first to validate the nephroprotective effect of WP. <i>P</i>. <i>sibiricum</i>, linking its multi-target effects (mTOR/ROS/apoptosis) to enhanced phytochemical potency. These findings support WP. <i>P</i>. <i>sibiricum</i> as a clinically translatable adjuvant for DDP-AKI.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Perfluorooctanoic acid (PFOA), a prototypical per- and polyfluoroalkyl substance (PFAS), is widely used in industrial and consumer products but is classified as a Group 1 carcinogen by the IARC due to its environmental persistence and bioaccumulation. PFOA primarily targets the liver, inducing stress responses and mitochondrial-mediated apoptosis, while promoting hepatoma cell proliferation through the mTOR pathway. To investigate the molecular mechanisms of PFOA-induced liver cancer (LIHC), we will use a network toxicology approach that integrates multi-omics data to construct a compound–target–disease network, focusing on potential targets like ALDH1B1, which encodes the aldehyde dehydrogenase family in the major pathway of alcohol metabolism. It is hypothesized that hepatic metabolic homeostasis is disrupted and hepatocellular carcinogenesis is ultimately promoted by PFOA through direct binding to ALDH1B1 and interference with its function. To confirm this, we will employ molecular docking and dynamics simulations to validate the binding interactions and toxicity mechanisms at the molecular level. This research aims to provide a comprehensive understanding of PFOA's hepatotoxicity and carcinogenicity while identifying potential targets for risk assessment and intervention strategies related to environmental exposure.
{"title":"Assessing the Carcinogenic Potential of PFOA: A Molecular Network Approach to Liver Toxicity","authors":"Libi Tan, Tianyu She, Siyan Huo, Rubing Lin, Nannan Cheng, Jing Li","doi":"10.1111/bcpt.70101","DOIUrl":"https://doi.org/10.1111/bcpt.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>Perfluorooctanoic acid (PFOA), a prototypical per- and polyfluoroalkyl substance (PFAS), is widely used in industrial and consumer products but is classified as a Group 1 carcinogen by the IARC due to its environmental persistence and bioaccumulation. PFOA primarily targets the liver, inducing stress responses and mitochondrial-mediated apoptosis, while promoting hepatoma cell proliferation through the mTOR pathway. To investigate the molecular mechanisms of PFOA-induced liver cancer (LIHC), we will use a network toxicology approach that integrates multi-omics data to construct a compound–target–disease network, focusing on potential targets like ALDH1B1, which encodes the aldehyde dehydrogenase family in the major pathway of alcohol metabolism. It is hypothesized that hepatic metabolic homeostasis is disrupted and hepatocellular carcinogenesis is ultimately promoted by PFOA through direct binding to ALDH1B1 and interference with its function. To confirm this, we will employ molecular docking and dynamics simulations to validate the binding interactions and toxicity mechanisms at the molecular level. This research aims to provide a comprehensive understanding of PFOA's hepatotoxicity and carcinogenicity while identifying potential targets for risk assessment and intervention strategies related to environmental exposure.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asli Sena Kücükyildiz, Mette Østergaard Thunbo, Christer Zøylner Swan, David P. Burgner, Jessica E. Miller, Therese Ovesen, Lars Henning Pedersen
Background
Congenital hearing loss (CHL) affects approximately 1–2 in 1000 children and significantly impacts development. Exposure to medications during pregnancy may impact offspring hearing; however, the ototoxic effects of different drugs have not been systematically investigated.
Methods
This systematic review and meta-analysis was conducted following PRISMA guidelines and analysed 21 experimental and observational studies examining 60 drugs across various categories.
Findings
Magnesium sulphate and systemic steroids, alone or in combination, showed potential protective effects towards CHL. Specific antibiotics (e.g., gentamicin and metronidazole) and non-steroidal anti-inflammatory drugs were associated with an increased risk of CHL. Modest evidence indicated that low-dose acetylsalicylic acid increased risk, whereas higher doses did not. Other drugs, such as anti-neoplastic agents and valproic acid, showed weaker associations with CHL. Most studies had methodological limitations.
Conclusion
Our findings highlight the urgent need for robust research to minimise preventable hearing loss in children.
{"title":"Maternal Exposure to Medications and the Risk of Congenital and Early-Onset Hearing Loss in Children: A Systematic Review and a Meta-Analysis","authors":"Asli Sena Kücükyildiz, Mette Østergaard Thunbo, Christer Zøylner Swan, David P. Burgner, Jessica E. Miller, Therese Ovesen, Lars Henning Pedersen","doi":"10.1111/bcpt.70090","DOIUrl":"https://doi.org/10.1111/bcpt.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Congenital hearing loss (CHL) affects approximately 1–2 in 1000 children and significantly impacts development. Exposure to medications during pregnancy may impact offspring hearing; however, the ototoxic effects of different drugs have not been systematically investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review and meta-analysis was conducted following PRISMA guidelines and analysed 21 experimental and observational studies examining 60 drugs across various categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Magnesium sulphate and systemic steroids, alone or in combination, showed potential protective effects towards CHL. Specific antibiotics (e.g., gentamicin and metronidazole) and non-steroidal anti-inflammatory drugs were associated with an increased risk of CHL. Modest evidence indicated that low-dose acetylsalicylic acid increased risk, whereas higher doses did not. Other drugs, such as anti-neoplastic agents and valproic acid, showed weaker associations with CHL. Most studies had methodological limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings highlight the urgent need for robust research to minimise preventable hearing loss in children.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karl-Hermann Sielinou Kamgang, Carina Lundby, Máté Szilcz, Kristina Johnell, Jonas W. Wastesson
Background
National estimates of drug discontinuation for deprescribing targets in older adults are limited, partly due to challenges distinguishing planned deprescribing from poor adherence. Focusing on individuals with multidose dispensing (MDD), characterized by high adherence by design, may yield realistic discontinuation rates.
Aims
To estimate the rates of discontinuation for chronically used drugs targeted for deprescribing among older adults, and to describe reinitiation among users of MDD and standard dispensing (non-MDD).
Methods
In this nationwide cohort study, Swedish adults aged ≥ 75 were identified from national registers. At baseline (1 January 2021), chronic users of seven drug classes were defined. We estimated the 12-month cumulative incidence of discontinuation (defined as no new dispensing during the treatment episode of the prior dispensing plus a 180-day grace period) and the proportion of patients restarting therapy within 180 days after discontinuation.
Results
We identified 162 518 chronic users: benzodiazepines (n = 69 511), PPIs (n = 43 973), antidepressants (n = 41 577), statins (n = 36 085), cholinesterase inhibitors (n = 6408), bisphosphonates (n = 5801) and antipsychotics (n = 4380). Discontinuation rates were low (8.3–51.5 per 1000 person-years), and non-MDD users had higher discontinuation and reinitiation rates across all drugs.
Conclusion
Discontinuation among Swedish older adults is infrequent. Irregular dispensing is likely misclassified as deprescribing, and MDD users may better reflect true discontinuation in routinely collected data.
{"title":"Discontinuing Chronic Medications Suggested for Deprescribing in Routine Clinical Practice: Nationwide Evidence From Routinely Collected Data in Swedish Older Adults","authors":"Karl-Hermann Sielinou Kamgang, Carina Lundby, Máté Szilcz, Kristina Johnell, Jonas W. Wastesson","doi":"10.1111/bcpt.70093","DOIUrl":"https://doi.org/10.1111/bcpt.70093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>National estimates of drug discontinuation for deprescribing targets in older adults are limited, partly due to challenges distinguishing planned deprescribing from poor adherence. Focusing on individuals with multidose dispensing (MDD), characterized by high adherence by design, may yield realistic discontinuation rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To estimate the rates of discontinuation for chronically used drugs targeted for deprescribing among older adults, and to describe reinitiation among users of MDD and standard dispensing (non-MDD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this nationwide cohort study, Swedish adults aged ≥ 75 were identified from national registers. At baseline (1 January 2021), chronic users of seven drug classes were defined. We estimated the 12-month cumulative incidence of discontinuation (defined as no new dispensing during the treatment episode of the prior dispensing plus a 180-day grace period) and the proportion of patients restarting therapy within 180 days after discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 162 518 chronic users: benzodiazepines (<i>n</i> = 69 511), PPIs (<i>n</i> = 43 973), antidepressants (<i>n</i> = 41 577), statins (<i>n</i> = 36 085), cholinesterase inhibitors (<i>n</i> = 6408), bisphosphonates (<i>n</i> = 5801) and antipsychotics (<i>n</i> = 4380). Discontinuation rates were low (8.3–51.5 per 1000 person-years), and non-MDD users had higher discontinuation and reinitiation rates across all drugs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Discontinuation among Swedish older adults is infrequent. Irregular dispensing is likely misclassified as deprescribing, and MDD users may better reflect true discontinuation in routinely collected data.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristie Rebecca Weir, Clémentine Tombez, Yvonne Mattmann, Sofia C. Zambrano, Eliza Ferguson, Katharina Tabea Jungo, Martina Zangger, Shana Volken, Enriqueta Vallejo-Yagüe, Renata Vidonscky Lüthold, Angela Edith Schulthess-Lisibach, Christof Bieri, Michaela Barbier, Pascal Juillerat, Sven Streit, Jennifer Inauen
Proton Pump Inhibitors (PPIs) are widely prescribed medications globally. PPIs are often inappropriately used – for example, prescribed without a clear indication, at higher-than-necessary doses, or for longer durations than needed – resulting in increased risks of adverse health outcomes such as nutrient deficiencies, osteoporosis-related fractures, and kidney disease. The effectiveness of current deprescribing interventions is inconsistent; this may relate to the misalignment with behavioural mechanisms, supporting the need for a mechanism-driven approach that targets key behavioural determinants. We co-designed a PPI deprescribing intervention with patients and health professionals for the Swiss primary care setting. This involved identifying behavioural determinants of PPI deprescribing from the literature at both the general practitioner (GP) and patient levels, mapping them to behaviour change techniques, selecting intervention elements, and developing contextualised intervention tools to effectively influence these determinants. The intervention tools were iteratively developed and assessed through qualitative methods with 16 patients and 18 health professionals. Participants considered the tools to be acceptable and practical for use in the Swiss primary care context.
{"title":"Development of a Deprescribing Intervention for Proton Pump Inhibitors in Primary Care: A Co-Design Approach With General Practitioners and Patients","authors":"Kristie Rebecca Weir, Clémentine Tombez, Yvonne Mattmann, Sofia C. Zambrano, Eliza Ferguson, Katharina Tabea Jungo, Martina Zangger, Shana Volken, Enriqueta Vallejo-Yagüe, Renata Vidonscky Lüthold, Angela Edith Schulthess-Lisibach, Christof Bieri, Michaela Barbier, Pascal Juillerat, Sven Streit, Jennifer Inauen","doi":"10.1111/bcpt.70091","DOIUrl":"https://doi.org/10.1111/bcpt.70091","url":null,"abstract":"<p>Proton Pump Inhibitors (PPIs) are widely prescribed medications globally. PPIs are often inappropriately used – for example, prescribed without a clear indication, at higher-than-necessary doses, or for longer durations than needed – resulting in increased risks of adverse health outcomes such as nutrient deficiencies, osteoporosis-related fractures, and kidney disease. The effectiveness of current deprescribing interventions is inconsistent; this may relate to the misalignment with behavioural mechanisms, supporting the need for a mechanism-driven approach that targets key behavioural determinants. We co-designed a PPI deprescribing intervention with patients and health professionals for the Swiss primary care setting. This involved identifying behavioural determinants of PPI deprescribing from the literature at both the general practitioner (GP) and patient levels, mapping them to behaviour change techniques, selecting intervention elements, and developing contextualised intervention tools to effectively influence these determinants. The intervention tools were iteratively developed and assessed through qualitative methods with 16 patients and 18 health professionals. Participants considered the tools to be acceptable and practical for use in the Swiss primary care context.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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