British journal of clinical pharmacology最新文献

{"title":"Patients on statins with elevated transaminases: Frequency of follow-up creatine kinase testing and gastroenterology referral.","authors":"Faris Shweikeh, Anas Kartoumah, Rajshri Joshi, Anjali Nadihaan, Mohammed Mouchli, Inderprit Singh","doi":"10.1002/bcp.70581","DOIUrl":"https://doi.org/10.1002/bcp.70581","url":null,"abstract":"<p><strong>Purpose: </strong>To quantify how often creatine kinase (CK) is measured after newly elevated aminotransferases in statin users, and whether absent CK data are associated with gastroenterology (GI) referrals.</p><p><strong>Methods: </strong>Retrospective chart review of adult outpatients on statins with a first alanine/aspartate aminotransferase (ALT/AST) elevation during a 5-year period at a large health system. The primary outcome was CK testing within 30 days; secondary outcomes included CK elevation rate and GI referral within 60 days.</p><p><strong>Results: </strong>Among 806 eligible patients, 22.8% (184/806) had CK measured within 30 days (median 9 days; IQR 5-17). Of those tested, 15.8% (29/184) had CK above the upper limit of normal (ULN); 3.6% (29/806) of the entire cohort therefore had unrecognized biochemical evidence of muscle injury. None had documented rhabdomyolysis, acute kidney injury or hospitalization. Among patients without timely CK testing (619/806), 4.7% (29/619) were referred to GI within 60 days; this proportion (3.6% of the total cohort) mirrored the fraction with CK elevation, suggesting potentially avoidable hepatic work-ups in the absence of muscle-specific testing.</p><p><strong>Conclusions: </strong>In routine practice, CK is infrequently measured after new ALT/AST elevations in statin users, yet a non-trivial subset has biochemical myopathy. Reflex CK testing at the first abnormal transaminase could improve diagnostic accuracy and reduce unnecessary GI referrals while preserving effective lipid-lowering therapy. Prospective evaluation of reflex-testing pathways and tailored statin selection/dosing is warranted.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811359","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":"Impact of empiric potassium supplementation on mortality, sudden cardiac arrest and stroke in furosemide initiators.","authors":"Thanh Phuong Pham Nguyen, Sean Hennessy, Colleen M Brensinger, Warren B Bilker, Laura M Dember, Todd A Miano, Tat-Thang Vo, Allison W Willis, Charles E Leonard","doi":"10.1002/bcp.70584","DOIUrl":"https://doi.org/10.1002/bcp.70584","url":null,"abstract":"<p><strong>Aim: </strong>A prior non-randomized study suggests that potassium supplementation may improve survival among furosemide initiators, and a randomized trial suggests that salt substitutes containing potassium might lower stroke risk. We conducted a retrospective cohort study using health-care data to confirm or refute these associations among new users of furosemide.</p><p><strong>Methods: </strong>The exposure of interest was empiric potassium dispensing (yes/no) concurrent with furosemide initiation. Outcomes were all-cause mortality, sudden cardiac arrest/ventricular arrhythmia (SCA/VA), and stroke. Primary as-started and secondary as-treated analyses were performed with Cox proportional hazards regression. We used inverse probability of treatment weighting (IPTW) to control for confounding, with weights calculated from high-dimensional propensity scores.</p><p><strong>Results: </strong>We identified 511 462 and 320 703 initiators of furosemide <40 and ≥40 mg/day with 21.5% and 35.3%, respectively, starting empiric potassium supplementation. In initiators of furosemide <40 mg/day with (vs. without) empiric potassium, as-started IPTW-hazard ratios (HRs) were 1.02 (95%CI 1.01-1.04) for death, 1.00 (0.94-1.04) for SCA/VA, and 1.03 (1.00-1.06) for stroke. Similarly, in initiators of furosemide ≥40 mg/day with (vs. without) empiric potassium, as-started IPTW-HRs were 1.02 (1.00-1.03) for death, 0.98 (0.94-1.03) for SCA/VA, and 1.01 (0.98-1.04) for stroke.</p><p><strong>Conclusion: </strong>We did not observe associations suggesting a clinically meaningful effect of empiric potassium supplementation among furosemide users. However, given the high prevalence of furosemide use among highly heterogeneous patient populations, a large pragmatic trial may be warranted to more definitively evaluate the potential benefits and harms of empiric potassium supplementation among furosemide initiators.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811344","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":"Effects of zibotentan and dapagliflozin combined in patients with compensated cirrhosis: A randomized placebo-controlled exploratory study.","authors":"Juan Carlos Garcia-Pagan, Lise Lotte Gluud, Mattias Mandorfer, Jörn M Schattenberg, Andrea De Gottardi, Annalisa Berzigotti, José Ignacio Fortea, Agustin Albillos Martínez, Edilmar Alvarado-Tapias, Marco Berning, Pawel Petryszyn, Emilia Henricson, Niklas Berglind, Min Lin, Kevin Persson, Anne-Kristina Mercier, Phil Ambery, Jaime Bosch, Jan Oscarsson, Don C Rockey","doi":"10.1002/bcp.70332","DOIUrl":"10.1002/bcp.70332","url":null,"abstract":"<p><strong>Aims: </strong>Endothelin A (ET_A) receptor antagonists may reduce cirrhosis-associated portal hypertension (PH). They are associated with fluid retention, which might be mitigated by sodium-glucose co-transporter 2 inhibitors (SGLT2is). Efficacy, safety and tolerability of combining the selective ET_A receptor antagonist zibotentan and the selective SGLT2i dapagliflozin were investigated.</p><p><strong>Methods: </strong>Patients with compensated cirrhosis (Child-Pugh A) were randomized 1:1 to zibotentan 2.5 mg plus dapagliflozin 10 mg (zibo/dapa) or placebo in a 6-week parallel, double-blind Phase II study. The absolute change in hepatic venous pressure gradient (HVPG) from baseline to week 6 was evaluated in the full analysis set using analysis of covariance.</p><p><strong>Results: </strong>In 28 participants (n = 14 per group), median age was 64 years (range: 37-78), common causes of cirrhosis were metabolic dysfunction-associated steatotic (46%) or alcohol-associated liver disease (39%), and 46% were receiving stable doses of non-selective beta-blockers. Baseline HVPG was 6.5-19 mmHg, and 16/28 had clinically significant portal hypertension. Absolute change in HVPG at week 6 was not different between groups (1.02 mmHg [90% CI -0.31, 2.35]). There was a trend towards decreased HVPG in patients with baseline HVPG ≥12 mmHg receiving zibo/dapa. Systolic and diastolic blood pressure were also reduced by zibo/dapa vs. placebo. Three mild adverse events (peripheral oedema) were reported (zibotentan/dapagliflozin, n = 2; placebo, n = 1). No serious adverse events or drug-induced liver injuries were observed.</p><p><strong>Conclusions: </strong>Combined zibo/dapa was well tolerated and had a good safety profile in patients with compensated cirrhosis, but had no conclusive effect on HVPG.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1326-1338"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707408","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":"Unintentional medication discrepancies and postoperative adverse drug events in patients with cancer: A prospective cohort study.","authors":"Atefeh Mehrabifar, Elizabeth Manias, Thomas Poulton, Bernhard Riedel, Janelle Penno, Patricia Nicholson","doi":"10.1002/bcp.70384","DOIUrl":"10.1002/bcp.70384","url":null,"abstract":"<p><strong>Aim: </strong>To understand regular medication management processes in the postoperative period for patients having major cancer surgery, and to evaluate whether medication discrepancies were associated with postoperative adverse drug events (ADEs).</p><p><strong>Method: </strong>A prospective cohort of 500 adult patients, undergoing planned major cancer surgery at a Melbourne specialist cancer hospital, was followed from surgery to day 30 postoperatively. Regular medication discrepancies were assessed across transitions of care up to five days postoperatively and at discharge. Adverse drug events were monitored up to 30 days after surgery. Multivariable logistic regression was used to identify predictors of medication discrepancies and ADEs.</p><p><strong>Results: </strong>Among 7254 medication orders for 500 patients, 12.5% (n = 905) of orders resulted in unintentional medication discrepancies. Polypharmacy (OR = 1.32; 95%CI: 1.21-1.44; p < 0.001) and length of stay (OR = 1.07; 95%CI: 1.03-1.12; p = 0.001) were significant predictors of unintentional medication discrepancies. ADEs occurred in 16.4% of patients (n = 82). In multivariable analysis, the odds of experiencing an ADE were significantly higher among patients who had unintentional discrepancies (vs. those with intentional discrepancies; OR = 3.06; 95%CI: 1.66-5.64; p < 0.001), older age (OR = 1.05; 95%CI: 1.02-1.08; p < 0.001), polypharmacy (OR = 1.20; 95%CI: 1.08-1.33; p < 0.001), higher acuity care admission (OR = 2.46; 95%CI: 1.33-4.54; p = 0.004) and prolonged hospital length of stay (OR = 1.07; 95%CI: 1.02-1.12; p = 0.002). Cardiovascular and alimentary tract medications were most commonly implicated in both discrepancies and ADEs.</p><p><strong>Conclusion: </strong>Unintentional medication discrepancies are associated with postoperative ADEs in patients having cancer surgery. Targeted strategies-especially for older patients, those with polypharmacy, and extended hospital stays-are essential to enhance medication safety across perioperative transitions.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1352-1361"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146217904","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":"An open-label, single-arm, dose-escalating concentration-QT study to investigate the cardiac effects and safety of paroxetine in healthy adults.","authors":"Sven C van Dijkman, Mathieu Félices, Bhaskar Pandurangavittal, Sanman Ghorpade, Caroline Easterbrook, Marcin Zabielski, Oscar Della Pasqua","doi":"10.1002/bcp.70398","DOIUrl":"10.1002/bcp.70398","url":null,"abstract":"<p><strong>Aims: </strong>Paroxetine is a selective serotonin reuptake inhibitor (SSRI), approved for treatment of major depressive disorder and anxiety disorders. Some SSRIs are known to prolong the QT interval; however, clinical evidence to establish a lack of association between paroxetine and corrected QT interval (QTc) prolongation is limited. Therefore, this study aimed to characterize the relationship between paroxetine concentration and QT/QTc interval following therapeutic doses in healthy individuals.</p><p><strong>Methods: </strong>This open-label, single-arm, dose-escalating concentration-QT study (NCT06065735) was performed in healthy adults (18-65 years) without a history of cardiac disease or pre-diagnosed mood disorder. Eligible individuals (n = 38) received paroxetine 20 to 60 mg QD for 1 week per dose level. Paroxetine plasma concentrations and electrocardiogram recordings were monitored over a 12 h period on Days 1 (baseline), 7 (20 mg), 14 (40 mg) and 21 (60 mg).</p><p><strong>Results: </strong>Mean change from baseline in QTcF (ΔQTcF) fluctuated between -7.1 and +4.7 ms. However, diurnal variation was also observed without treatment. A linear regression model showed no clinically significant effect of paroxetine concentrations on ΔQTcF, with a weak slope of 0.0108 ms/ng/mL (90% CI: 0.01, 0.03) and maximum ΔQTcF of +0.42 ms (90% CI: -2.68, 3.52) at 60 mg QD, corresponding to a Cmax of 221.4 (95%CI: 179.6-272.8) ng/mL. Similarly, paroxetine did not affect the mean change in PR or QRS interval, or heart rate relative to baseline.</p><p><strong>Conclusions: </strong>Paroxetine does not prolong QTc interval in healthy individuals to any clinically meaningful extent at therapeutically relevant doses. This study supports the favourable cardiac safety profile of paroxetine.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1385-1396"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-informed precision dosing of carboplatin in cancer patients by leveraging myelosuppression data from electronic health records.","authors":"Alessandro De Carlo, Elena Maria Tosca, Mirjam Crul, Tim Schutte, Lia van Zuijlen, Idris Bahce, Medhat M Said, Jan Buter, Harmen Huls, Paolo Magni, Imke Bartelink","doi":"10.1002/bcp.70413","DOIUrl":"10.1002/bcp.70413","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to develop and validate a population pharmacokinetic-pharmacodynamic (pop-PK-PD) model to describe carboplatin-induced myelosuppression in cancer patients and support dose individualization.</p><p><strong>Methods: </strong>Data from 580 cancer patients treated with carboplatin at Amsterdam UMC between 2019 and 2022 were used for model development, focusing on lung, gynaecological and gastric/oesophageal cancers. Platelet (PLT) and neutrophil (NT) counts, along with patient-specific covariates (e.g., age, serum albumin, eGFR), were extracted from Electronic Health Records and used in the analysis. Given the absence of pharmacokinetic (PK) samples, PK parameters were derived from a literature carboplatin pop-PK model. Model applicability to inform personalized carboplatin dosing was evaluated on a separate cohort of 210 patients treated between 2022 and 2024 in the same centre.</p><p><strong>Results: </strong>Two joint Friberg models effectively described carboplatin-induced myelosuppression. Serum albumin, eGFR and paclitaxel and pemetrexed co-medications were included in the final model. On the test cohort, >85% of NT and >87% of PLT observations fell within the 90% confidence interval of Bayesian model predictions, confirming that the model can support dose adjustments for subsequent treatment cycles. An example of model-based dose adjustments is also presented with a simulation study.</p><p><strong>Conclusions: </strong>The pop-PK-PD model demonstrated strong performance in describing and predicting carboplatin-induced myelosuppression, thus providing a valuable strategy for dose personalization. Further refinements and validation steps are needed before integrating such an approach into clinical workflows.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1457-1472"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the influence of transfusion and blood loss on tranexamic acid concentration in scoliosis surgery with blood loss.","authors":"Paula Alexandra Sá, Luisa Barreiros, Marcela A Segundo, Eugénia Cruz, Sibylle Langenecker","doi":"10.1002/bcp.70402","DOIUrl":"10.1002/bcp.70402","url":null,"abstract":"<p><strong>Aims: </strong>Tranexamic acid (TXA) stabilizes clot formation by inhibiting fibrin degradation and improves postoperative outcomes. However, rare adverse events (e.g., thrombosis, seizures) warrant dose-risk evaluation. This study examines how perioperative blood loss and transfusion practices affect TXA concentrations during paediatric scoliosis surgery.</p><p><strong>Methods: </strong>Forty-three patients undergoing scoliosis surgery with TXA were retrospectively analysed. The study assessed the impact of packed red blood cell (PRBC) transfusion on plasma TXA levels and whether maintaining concentrations ≥10 μg/mL correlated with intraoperative blood loss. TXA levels were measured using UHPLC-MS/MS.</p><p><strong>Results: </strong>Median TXA concentration 30 min after the loading dose was 37.8 μg/mL (IQR: 31.4-39.6 μg/mL), decreasing to 10.6 μg/mL (IQR: 9.7-13.5 μg/mL) after transfusion. At surgery end, the mean concentration was 12.9 ± 2.5 μg/mL. Thirty-one patients maintained TXA levels ≥10 μg/mL, associated with ~80% inhibition of tissue plasminogen activator. Of six patients below this threshold, five had received transfusions. A significant correlation was found between higher intraoperative blood loss and lower TXA levels, consistent with a dilutional effect. In contrast, among patients with TXA ≥ 10 μg/mL, correlation with blood loss was weak (Spearman's ρ = -0.11, p = 0.54). Findings suggest homologous PRBC transfusion reduces plasma TXA through volume expansion.</p><p><strong>Conclusions: </strong>Sustaining TXA concentrations >10 μg/mL is essential for antifibrinolytic efficacy and haemostatic outcomes. The dilutional impact of PRBC transfusion underscores the need for intraoperative dose adjustment. Optimizing TXA dosing requires understanding pharmacokinetics and patient variability.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1397-1405"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypnotic doses of fazamorexant induced less impairment on balance and cognition than zolpidem in healthy younger and elderly individuals.","authors":"Chen Xia, Huang Xingxing, Jin Lu, Wang Ruwei","doi":"10.1002/bcp.70414","DOIUrl":"10.1002/bcp.70414","url":null,"abstract":"<p><strong>Aims: </strong>Fazamorexant is a dual orexin receptor antagonist being developed for the treatment of insomnia. This study aims to determine the dose-exposure-response relationship of single-dose fazamorexant vs. zolpidem in young adult and elderly healthy Chinese volunteers.</p><p><strong>Methods: </strong>This single-centre, randomized, double-blind, double-dummy, placebo- and active-controlled, 4-period crossover study administered fazamorexant (40 mg/80 mg to young adults; 20 mg/40 mg to the elderly) and zolpidem (10 mg). Pharmacokinetics, pharmacodynamics (primary endpoint: SPV) and safety were assessed.</p><p><strong>Results: </strong>Following a single 40 mg oral dose of fazamorexant in elderly and young adults, the geometric least‑squares mean (GLSM) values for C_max were 1527.05 ng/mL (95% CI: 1268.66-1838.06) in the elderly and 1652.52 ng/mL (95% CI: 1420.41-1922.56) in young adults. The corresponding GLSM AUC_0-t values were 7815.91 h·ng/mL (95% CI: 5985.56-10205.97) and 8351.15 h·ng/mL (95% CI: 6716.38-10383.84), respectively. There was no significant pharmacokinetic difference between young adults and the elderly with fazamorexant (C_max GMR 92.41% [90% CI: 75.84-112.59]; AUC_0-t GMR 93.59% [90% CI: 70.43-124.37]). In general, high-dose fazamorexant caused similar or less impairment vs. zolpidem in eye movements (SPV: young adults: 110.4 ± 80.1 vs. 108.3 ± 82.7 deg/sec；elderly: 145.1 ± 64.2 vs. 185.5 ± 63.0 deg/sec), choice-reaction-time performance, body sway and memory tests in young and elderly cohorts. The effects of low-dose fazamorexant on these psychomotor and cognitive measurements were significantly smaller than those of high-dose fazamorexant and zolpidem in both age cohorts. Despite of similarity in exposure, fazamorexant demonstrated larger effects on the pharmacodynamic measurements in the elderly than in young adults, suggesting an age-related increase of pharmacological sensitivity.</p><p><strong>Conclusions: </strong>Clinically hypnotic doses of fazamorexant induced less balance, judgement and memory impairment in healthy adults and elderly volunteers compared to the comprehensive suppression of zolpidem on the neurological system. These preliminary results suggest that fazamorexant is a potentially safer drug for insomnia. No age-related pharmacokinetic difference was identified with fazamorexant.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1473-1486"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and impact of prescribing cascades in community-dwelling adults: Longitudinal analysis of the Irish longitudinal study on ageing (TILDA).","authors":"Ann Sinéad Doherty, Rose Anne Kenny, Frank Moriarty, Fiona Boland, Barbara Clyne, Tom Fahey, Denis O' Mahony, Emma Wallace","doi":"10.1002/bcp.70425","DOIUrl":"10.1002/bcp.70425","url":null,"abstract":"<p><p>Prescribing cascades occur when medication is prescribed to prevent/treat the adverse effects of another medication and may be intentional/unintentional. This study examines the prevalence of nine prescribing cascades (ThinkCascades) in The Irish Longitudinal StuDy on Ageing (TILDA). A prospective cohort study examined those aged ≥50 years with three consecutive data collection waves (N = 6118) recorded between Wave 1 (2009/2011) and Wave 5 (2018). Nine separate analysis sets were created, representing each ThinkCascade. Exposure was the incident use of Drug A at wave x. A prescribing cascade was defined as the incident use of Drug B at wave x + 1, with continued use of Drug A. Five out of nine ThinkCascades were identified over 9 years of follow-up. Overall, 24 participants experienced at least one ThinkCascade, representing a 2.1% prevalence (n = 1153 eligible). This low prevalence may indicate prescribers' awareness of prescribing cascades. Higher event rates are required to examine any association with adverse health outcomes.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1500-1508"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a clinical risk score nomogram for predicting clozapine plasma concentrations below 350 ng/mL: A retrospective cohort study.","authors":"Jing Ding, Jiarui Liu, Yuanyuan Zhai, Xiaohua Cui, Suo Zhang, Jiao He, Ying Chen","doi":"10.1002/bcp.70411","DOIUrl":"10.1002/bcp.70411","url":null,"abstract":"<p><strong>Aims: </strong>A plasma clozapine concentration below 350 ng/mL may result in treatment failure; however, a rapid method for predicting whether a patient's plasma concentration meets this threshold is lacking. This study aimed to develop a nomogram to predict the risk of subtherapeutic clozapine concentrations in treated patients.</p><p><strong>Methods: </strong>Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic clozapine concentrations. A predictive nomogram prediction model was then constructed based on these factors. The ethics committee of the Xi'an Mental Health Center approved the study (XAJWKY-2024034).</p><p><strong>Results: </strong>Multivariate logistic regression analysis identified daily dose (OR = 0.987, 95% CI: 0.984-0.990, P < 0.001) and sex (OR = 3.863, 95% CI: 2.597-5.746, P < 0.001) as independent factors influencing the subtherapeutic concentrations of clozapine. A predictive nomogram was constructed based on a multivariable prediction model, which demonstrated good accuracy and discriminative ability, with an area under the curve of 0.760. Validation of the model's calibration curve resulted in a concordance index of 0.764. A decision curve analysis revealed that the nomogram predicting the risk of subtherapeutic plasma clozapine concentrations exhibited a greater net benefit value, ranging from 10% to 62%. Additionally, our research indicated that the daily dosage of clozapine required for male patients to achieve a plasma concentration of 350-600 ng/mL ranges from 228.8 to 392.2 mg, whereas it ranges from 154.2 to 264.3 mg for female patients.</p><p><strong>Conclusions: </strong>The constructed nomogram was effective at predicting the risk level associated with subtherapeutic clozapine plasma concentrations.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":"1445-1456"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803239","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}