British journal of clinical pharmacology最新文献

{"title":"The prevalence of polypharmacy increases with age among patients with inflammatory bowel disease: A nationwide cohort study.","authors":"Ken Lund, Jesper Ryg, Torben Knudsen, Jens Kjeldsen, Jan Nielsen, Sonia Friedman, Jimmy K Limdi, Bente Mertz Nørgård","doi":"10.1002/bcp.70159","DOIUrl":"https://doi.org/10.1002/bcp.70159","url":null,"abstract":"<p><strong>Aims: </strong>Polypharmacy is common in adult patients with inflammatory bowel disease (IBD). This study aims to quantify medication prescriptions and estimate the risk of polypharmacy over time in older adults with IBD.</p><p><strong>Methods: </strong>In a nationwide cohort of adult incident IBD patients from 1 April 1996, to 31 December 2019, we examined medication prescriptions across calendar years among young adults (18-39 years), adults (40-59 years), older adults (60-79 years) and oldest adults (≥80 years). The prescriptions (ATC:level-3) were grouped into 0, 1-4, 5-9 (moderate polypharmacy) and ≥10 (excessive polypharmacy) and described 1 year pre-IBD diagnosis, and 1, 2 and 3 years post-IBD diagnosis. We estimated the risk of polypharmacy (moderate and excessive) 1-year post-IBD diagnosis in patients (≥60 years) using regression models, comparing recent to early years.</p><p><strong>Results: </strong>We included 21 255 young adults, 13 432 adults, 8271 older adults and 933 oldest adults. The prevalence of moderate polypharmacy 1-year post-IBD diagnosis for young adults, adults, older adults and the oldest adults was 15.1, 23.2, 38.1 and 49.4%, respectively. The corresponding proportions for excessive polypharmacy were 1.5, 5.4, 16.6 and 23.4%, respectively. The adjusted odds ratio for polypharmacy among patients ages ≥60 years in 2020 vs. 1997 was 1.02 (95% confidence interval: 0.71-1.47).</p><p><strong>Conclusion: </strong>The prevalence of polypharmacy was high and increased with increasing age. In all age groups, the year-by-year level of polypharmacy was stable. For patients aged ≥60 years, there were no signs of a decreasing trend. Polypharmacy seems to be an existing problem and awareness of ensuring appropriate prescribing is warranted.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health technology assessment (HTA): Decisions on treatment efficiency guided by clinical judgement and pharmacoeconomics.","authors":"Kenneth R Paterson, David J Webb","doi":"10.1002/bcp.70157","DOIUrl":"https://doi.org/10.1002/bcp.70157","url":null,"abstract":"<p><p>Over the past 25 years, the UK has adopted health technology assessment (HTA) as a mechanism to ensure that new medicines, and new indications for existing medicines, are assessed in an open, objective and robust way so that when the UK National Health Service (NHS) adopts these therapeutic developments, it does so in a cost-effective manner, accepting those agents with an acceptable cost per quality-adjusted life year (QALY) or a discount that brings the cost below the threshold. Usually, pharmacoeconomic modelling is used to justify pricing, often relying on surrogate endpoints or extrapolation beyond the duration of existing trials data. Although cost-effectiveness is often based on robust clinical trials, there are other issues to consider, which require an understanding of clinical pharmacology and clinical judgement. Key considerations include the justification of use of surrogates and extrapolation, the appropriateness of any comparator drug studied, the difference between efficacy in trials and clinical effectiveness in real-world use, the additional costs of providing a service to deliver the medicine, and the cost of any important adverse effects that are likely to occur. Although the process in the UK is now well established, with support from clinicians and the public, there remain questions about whether the currently accepted cost/QALY is set too high, whether a special case should be made for some drugs commanding a higher cost/QALY (such as in cancer and end-of-life situations), and whether HTA should be used more broadly to assess other activities undertaken by the NHS.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The problem of propranolol poisoning.","authors":"Hayley Williams, Pardeep Jagpal, Euan Sandilands, Emma Morrison, Laurence Gray, Harry Krishna Ruben Thanacoody, Elisha Beg, Sally Bradberry, Robin Ferner","doi":"10.1002/bcp.70147","DOIUrl":"https://doi.org/10.1002/bcp.70147","url":null,"abstract":"<p><strong>Aims: </strong>Propranolol is licensed in the UK and elsewhere to relieve symptoms of anxiety. In overdose, propranolol poisoning can be serious, difficult to treat and potentially fatal. This paper describes cases of intentional propranolol overdose reported to the UK National Poisons Information Service in order to raise awareness of the risk of harm following propranolol overdose and support safer prescribing.</p><p><strong>Methods: </strong>This study reviews enquiries to UK Poison Centres involving intentional overdoses of propranolol requiring hospital attendance and reported between 1 January 2022 and 31 December 2023.</p><p><strong>Results: </strong>There were 444 enquiries about 363 intentional propranolol overdoses in 359 different patients (248 [69%] women). Median age [interquartile range, IQR] was 32 [22-45] years (n = 355); 52 (14%) patients were <18 years old. The indication was known in 121 (33%) cases, and was anxiety in 111. In 43/61 cases where propranolol and an antidepressant were co-prescribed, patients took both in overdose. The outcome was confirmed in 159 (44%) exposures; 110 patients recovered completely, 13 had ongoing features, one had permanent sequelae, and 35 died.</p><p><strong>Conclusions: </strong>Overdose patients were often prescribed propranolol for anxiety, and many developed systemic toxicity. Despite intensive treatment, many patients still die from poisoning with propranolol alone or in combination with other agents. Given the dangers of propranolol in overdose, prescribers based in primary care settings should recognize that using propranolol to manage anxiety can be dangerous.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A study on adverse events of botulinum toxin type A in real-world applications: A FAERS database analysis.","authors":"Weizhen He, Jian Guo, Yingqian Xu, Xiaoling Huang, Kaiqin Chen","doi":"10.1002/bcp.70141","DOIUrl":"https://doi.org/10.1002/bcp.70141","url":null,"abstract":"<p><strong>Aims: </strong>Botulinum toxin type A (BoNT-A) is widely used for its efficacy in treating a variety of neuromuscular disorders. However, data on its safety and adverse events (AEs) in real-world settings remain limited. The Food and Drug Administration Adverse Event Reporting System (FAERS) database provides an invaluable resource for evaluating the safety of BoNT-A.</p><p><strong>Methods: </strong>We used four methods to evaluate the disproportionality of AEs associated with BoNT-A: the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS).</p><p><strong>Results: </strong>Among the 17 307 196 case reports in the FAERS database, there were 69 644 reports where BoNT-A was listed as the \"primary suspect\" for AEs. BoNT-A-related AEs affected 27 system organ classes (SOCs). Based on the four algorithms, 290 significant disproportionalities at the Preferred Term (PT) level were retained. Unexpected AEs, such as skin wrinkles, hyperacusis, Guillain-Barré syndrome, mediastinitis and infective aneurysm, were identified, which are not mentioned in the product insert.</p><p><strong>Conclusion: </strong>This study provides an overview of AEs in the real-world use of BoNT-A, revealing its broad safety profile. Although the majority of AEs were mild to moderate, there is a need to remain vigilant for serious AEs and to monitor them in clinical practice.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spotlight commentary: Treatment of multidrug-resistant Gram-negative infections in the era of growing antimicrobial resistance.","authors":"Luka Bielen, Andro Vujević, Luka Csenar","doi":"10.1002/bcp.70155","DOIUrl":"https://doi.org/10.1002/bcp.70155","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic medicine management systems in developing countries: A landscape review.","authors":"Andrew Lambarth, Dalia Wainwright, Trisha Saha, Millicent Banks, Iona Minty, P A M K Abeywickrama, Reya V Shah, Yogini Jani, Reecha Sofat","doi":"10.1002/bcp.70156","DOIUrl":"https://doi.org/10.1002/bcp.70156","url":null,"abstract":"<p><p>Medicines are a major global health expense. However, suboptimal use increases costs and causes patient harm. One way to reduce costs and increase safe, efficient medicines use is with electronic medicines management systems (EMMS). They allow easy capture of routine health data which can facilitate research, service planning and reimbursement processes. There are various barriers to healthcare digitization in developing countries (DCs), although some have overcome these. We sought to understand the landscape of EMMS use in DCs. We systematically searched six bibliographic databases from inception to 23 October 2024 for studies reporting the implementation and/or use of EMMS in countries with lower than 'very high' Human Development Index (HDI). We qualitatively and quantitatively summarized data on geographic location, healthcare setting and system functionality. We created an interactive map illustrating spatial and temporal trends in EMMS use. A total of 314 records described the use of EMMS in 45 DCs, 206 of which described coexistence/integration of other health data (e.g., electronic health records [EHR]). Predominantly, EMMS were for prescribing (n = 264) or dispensing (n = 66), implemented in secondary care settings and operated locally rather than regionally or nationally. Common EMMS use-cases included adherence monitoring in human immunodeficiency virus (HIV) and tuberculosis treatment. Our findings highlight both widespread EMMS adoption-commonly in the context of a broader EHR-and persistent gaps in implementation. These insights could be used by policymakers and healthcare leaders to guide strategy and funding decisions. Existing systems could be leveraged for service planning, healthcare delivery and optimizing medicine use. Where EMMS are not yet in use, our findings provide a roadmap for stakeholders to identify and emulate successful implementations in similar healthcare settings. Expanding the interoperability and scale of EMMS could further enable transformative digital technologies, increasing efficiencies and coverage, and ultimately improving patient outcomes.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCC4 polymorphism indirectly reduces systemic exposure to a capecitabine metabolite 5'-deoxy-5-fluorouridine in Japanese subjects.","authors":"Natsumi Matsumoto, Ayano Oishi, Shotaro Yoshino, Yusuke Masuo, Yutaro Kubota, Hiroo Ishida, Ken Shimada, Yukio Kato, Ken-Ichi Fujita","doi":"10.1002/bcp.70152","DOIUrl":"https://doi.org/10.1002/bcp.70152","url":null,"abstract":"<p><strong>Aims: </strong>Capecitabine converts to 5-fluorouracil (5-FU) in 3 steps. We previous demonstrated a significant association between area under the plasma concentration-time curve (AUC) of a metabolite 5'-deoxy-5-fluorouridine (5'-DFUR) and capecitabine-induced toxicity. However, critical factors affecting the 5'-DFUR AUC remain unclear. This study investigated the effects of the ABCC4 rs3742106 (G > T) which down regulates ABCC4 protein expression, on 5'-DFUR AUC, and analysed the underlying mechanisms.</p><p><strong>Methods: </strong>ABCC4 rs3742106 and 5'-DFUR AUC were prospectively analysed in 37 Japanese patients with colorectal cancer who received capecitabine plus oxaliplatin. 5'-DFUR transport was analysed using ABCC4-expressing membrane vesicles. A physiologically based pharmacokinetic (PBPK) model was constructed to identify potential drug-metabolizing enzymes responsible for 5'-DFUR AUC and affected by rs3742106. ABCC4 expression in human hepatoma HepaRG cells was suppressed by small interfering RNA against ABCC4, followed by gene expression measurement of the enzymes.</p><p><strong>Results: </strong>AUC/dose of 5'-DFUR in patients with ABCC4 rs3742106 G/T or T/T genotype was significantly lower than other patients (P = .0258). However, 5'-DFUR was not transported by ABCC4 expressed in membrane vesicles. PBPK model analyses revealed that activity of thymidine phosphorylase (TP), which converts 5'-DFUR to 5-FU, may be increased by the ABCC4 rs3742106, most strongly contributing to the decrease in 5'-DFUR AUC. Transfection of siABCC4 in HepaRG cells increased intracellular cyclic adenosine monophosphate (cAMP) and enhanced TP mRNA expression. Addition of a cAMP analogue, 8-bromo-cAMP, also induced TP mRNA.</p><p><strong>Conclusion: </strong>The ABCC4 polymorphism reduces 5'-DFUR AUC by an indirect mechanism. An increase in hepatic cAMP, which upregulates TP expression, was proposed as a hypothetical mechanism for this polymorphic change.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current evidence and insights on single vs. double dose of basiliximab in adult solid organ transplant recipients: A systematic review.","authors":"Alessio Provenzani, Braidon A Lape, Anneliese M Harp, Victoria Weisbrod, Lavinia Piazza","doi":"10.1002/bcp.70151","DOIUrl":"https://doi.org/10.1002/bcp.70151","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this systematic review was to assess all available clinical data regarding the use of a single dose of basiliximab in solid organ transplantation compared to the standard double dosage, with particular interest in efficacy, safety and cost-savings.</p><p><strong>Methodology: </strong>A systematic review was performed following PRISMA guidelines by searching PubMed, Web of Science, Ovid MEDLINE and Google Scholar for studies from 2000 to 2024 evaluating single-dose basiliximab in adult transplant recipients. Screening was based on PICOS criteria and MeSH terms. After removing duplicates and applying filters (English, full text, adults, clinical trials and observational studies), three eligible studies were included. Risk of bias was assessed using the ROBINS-I-V2 tool.</p><p><strong>Results: </strong>All three included studies demonstrated comparable outcomes between single and double-dose basiliximab regimens. Acute cellular rejection ranged from 4.3% to 12.3%, and graft loss occurred in 0% to 2.9% of patients. Patient survival remained elevated across studies, ranging from 95.6% to 100%. Concerning safety, no major differences were reported in overall infection rates or hospital readmissions. Cost-savings favoured the single-dose regimen across all studies. Reported per-patient savings ranged from approximately US$2100 to US$4400, with institutional savings up to US$697864.</p><p><strong>Conclusion: </strong>A single dose of basiliximab can be a reasonable and cost-saving option, with comparable efficacy and safety, reducing drug expenses. This change in the maintenance regimen suggests that the initial induction therapy can be slightly reduced without affecting efficacy, as supported by the reviewed studies, which is promising for future research.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The synergistic effect of anticholinergic burden and depression on fall risk in older persons.","authors":"Raymond Salet, Nathalie van der Velde, Didi Rhebergen, Bob van de Loo, Lotta Seppala, Natasja M van Schoor, Bruno Stricker, Marieke Henstra","doi":"10.1002/bcp.70148","DOIUrl":"https://doi.org/10.1002/bcp.70148","url":null,"abstract":"<p><strong>Aims: </strong>Both anticholinergic burden (ACB) and depression are known to increase fall risk in older persons, next to increasing morbidity and mortality. However, the effect of depression on fall risk associated with ACB is unclear. This is relevant because several antidepressants have anticholinergic effects to some extent. The aim of this study was to assess the relationship between ACB and falls, and the impact of depression on this relationship.</p><p><strong>Methods: </strong>We cross-sectionally examined the relationship between both ACB and clinical depression and falls in the past 12 months, in a harmonized cohort of Dutch community dwelling persons (n = 7884). For all analyses, we calculated adjusted odds ratios (ORs) and their 95% confidence intervals (CI). We also investigated the impact of depression on the relationship between ACB and falls, by calculating their interaction on both an additive and multiplicative scale.</p><p><strong>Results: </strong>Both a high ACB score (≥3) and clinical depression were independently significantly associated with falls in the past 12 months. Additionally, there was a statistically significant interaction (P = 0.038) between ACB and clinical depression on fall risk, both on an additive and multiplicative scale (1.13 and 1.44 respectively).</p><p><strong>Conclusions: </strong>In older persons, the presence of clinical depression strengthened the association between ACB and falls. We discourage withholding pharmacological treatment to avoid falls, despite the ACB of antidepressants. In the case of depression, we recommend considering non-pharmacological alternatives; choose pharmacological interventions with the lowest risk of adverse events; assess and treat other fall risk factors; and perform multidisciplinary medication review to minimize (accumulation of) ACB.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: 'Methotrexate toxicity and glucarpidase: A call for dose optimization'.","authors":"Arjen Koppen, Maaike A Sikma, Frederike K Engels, Marise R Heerma van Voss, Martine E D Chamuleau, Imke H Bartelink, Marieke A Dijkman","doi":"10.1002/bcp.70164","DOIUrl":"https://doi.org/10.1002/bcp.70164","url":null,"abstract":"","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}