Clinical Drug Investigation最新文献

{"title":"The Economic Burden of HDV in Italy: Evaluating the Potential Impact and Effects of Bulevirtide for Chronic HDV Infection.","authors":"Martina Paoletti, Daniela Cazzato, Andrea Marcellusi, Loreta A Kondili, Nicola Coppola, Barbara Coco, Alessandra Mecozzi, Sara Mollea, Chong Kim, Marvin Rock","doi":"10.1007/s40261-026-01598-0","DOIUrl":"https://doi.org/10.1007/s40261-026-01598-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic hepatitis D is associated with substantial clinical and economic burden due to its progressive course and risk of severe liver-related complications. The aim of this study was to quantify the economic burden of chronic hepatitis D (HDV) in Italy from societal perspectives, and to estimate the clinical and economic consequences associated with bulevirtide, peginterferon alfa (PEG-IFN-α), and best supportive care (BSC) in HDV-RNA-positive adults with compensated liver disease.</p><p><strong>Methods: </strong>The economic impact of HDV infection was estimated using a cost-of-illness (COI) analysis, while the costs and effects of introducing bulevirtide were estimated using a cost-and-outcomes analysis (COA). The COA compared two scenarios: a clinical practice scenario that includes PEG-IFN-α and BSC, and a scenario that introduces bulevirtide. The analyses were conducted from the societal perspective; therefore, direct and indirect estimated costs were included. The most relevant outcomes were quality adjusted life years (QALYs) and the number of deaths. Both analyses were carried out on a standardised hypothetical cohort of 1000 HDV-RNA-positive adult patients with compensated liver disease, over 10 years. A deterministic sensitivity analysis (DSA) was conducted to assess parameter uncertainty.</p><p><strong>Results: </strong>The COI estimated a 10-year economic burden of €34,939,429.41 for the management and treatment of patients with HDV infection in Italy. The COA estimated a total 10-year reduction in disease-related costs of €2,152,752.76 after the introduction of bulevirtide, an increase of 8.26% (+ 366.12) in the number of QALYs gained, and a 12.39% reduction (- 73.67) in the number of deaths.</p><p><strong>Conclusions: </strong>Our study suggests that the introduction of bulevirtide may alleviate the clinical and economic burden associated with HDV in Italy, while improving quality of life.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179626","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":"Formulation-Specific Safety Issues of HIV Pre-exposure Prophylaxis Drugs: A Disproportionality Analysis of the FAERS Database.","authors":"Davide Rozza, Elisabetta Poluzzi, Ippazio Cosimo Antonazzo, Angela Boccia, Marco Paccini, Fortuna Gallucci, Domenico Ponticelli, Giulio Geraci, Fernando Agüero, Giampiero Mazzaglia, Lorenzo Giovanni Mantovani, Emanuel Raschi, Pietro Ferrara","doi":"10.1007/s40261-026-01602-7","DOIUrl":"https://doi.org/10.1007/s40261-026-01602-7","url":null,"abstract":"<p><strong>Background and objective: </strong>As human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) use expands, real-world post-marketing safety evidence remains limited, particularly regarding potential formulation-specific adverse-event patterns across oral and long-acting agents. We aimed to characterise the post-marketing safety profiles of FDA-approved PrEP drugs using the FDA Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) data from 2012 to 2024. Individual Case Safety Reports (ICSRs) listing emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), emtricitabine/tenofovir alafenamide (FTC/TAF) or cabotegravir (CAB) as suspected PrEP drugs were included. Two comparator groups were used: all non-PrEP ICSRs and ICSRs involving non-PrEP HIV drugs. Disproportionality was evaluated at the MedDRA high-level term (HLT) level using reporting odds ratios and 95% confidence intervals (CIs), identifying signals of disproportionate reporting (SDRs) with a lower bound of the 95%CIs > 1. Sensitivity analyses explored sex, reporter type, and indication.</p><p><strong>Results: </strong>We identified 3201 PrEP-related ICSRs (FTC/TDF: 2688; FTC/TAF: 463; CAB: 50), predominantly involving young adult males. FTC/TDF exhibited a broad pattern of SDRs-including renal/metabolic abnormalities, muscular signals, mucosal disorders and some previously under-characterised signals-many of which attenuated when using HIV-treated comparators. FTC/TAF showed a narrower, highly consistent pattern dominated by hepatobiliary and metabolic monitoring procedures, renal function evaluations and neurosensory disturbances. CAB showed specific, reproducible signals for injection-site, dermatologic and procedure-related events.</p><p><strong>Conclusions: </strong>PrEP agents display distinct, formulation-specific and reproducible safety patterns in FAERS. Comparator choice substantially influences the detection and interpretation of SDRs and can help distinguish reproducible formulation-related reporting patterns from findings that may be driven by the clinical and reporting context. These insights highlight priority areas for future research.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163671","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":"Cognitive Outcomes After Reperfusion Therapy for Acute Ischaemic Stroke: A Systematic Review and Meta-analysis and the PRECISE-ACTION Framework for Transdisciplinary Cognitive Management.","authors":"Samprithi Raja, Robert Weissert, Zeljka Calic, Pravin Thomas, Jasvinder Chawla, Susana Mederer Hengstl, Ivica Smokovski, Olga Golubnitschaja, Tomotaka Tanaka, Kevin J Spring, Murray C Killingsworth, Man Mohan Mehndiratta, Rajesh N Kalaria, Masafumi Ihara, Sonu M M Bhaskar","doi":"10.1007/s40261-026-01596-2","DOIUrl":"https://doi.org/10.1007/s40261-026-01596-2","url":null,"abstract":"<p><strong>Background: </strong>Post-stroke cognitive impairment (PSCI) is disabling after acute ischaemic stroke (AIS), but cognitive outcomes after reperfusion therapy remain uncertain because studies differ in treatment pathways, cognitive tools, follow-up timing, and ascertainment.</p><p><strong>Objectives: </strong>To estimate PSCI prevalence after AIS reperfusion therapy and evaluate comparative cognitive, safety, and functional outcomes.</p><p><strong>Methods: </strong>This systematic review and meta-analysis searched PubMed/MEDLINE, Embase, and CENTRAL from 1 January 2000 to 31 May 2024, with an updated search on 16 June 2026. Random-effects models were used. Risk ratios (RRs) were the primary comparative binary measure; odds ratios (ORs) were sensitivity analyses.</p><p><strong>Results: </strong>Twenty-eight distinct study records comprising 18,322 participants were included in this meta-analysis. Pooled PSCI prevalence was 33% in treatment-arm analyses (95% CI 14-54%; I² = 99.48%) and 39% in overall or single-arm cohorts (95% CI 24-56%; I² = 99.60%). Extreme between-study heterogeneity (I² ≈ 99%) limited the precision and generalisability of the pooled prevalence estimates. Reperfusion therapy was not associated with PSCI risk (RR 1.10, 95% CI 0.94-1.29; p = 0.241); OR sensitivity analysis was consistent (OR 1.26, 95% CI 0.91-1.75; p = 0.169). Continuous cognitive outcomes showed a pooled standardised mean difference of 0.67 (95% CI 0.16-1.18; p = 0.010), with substantial heterogeneity.</p><p><strong>Conclusions: </strong>Post-stroke cognitive impairment remains frequent after AIS reperfusion therapy, affecting approximately one-third of reperfusion-treated patients and two-fifths of overall or single-arm cohorts. Comparative RR and OR analyses did not show a robust overall association between reperfusion exposure and PSCI risk, while cognitive score differences were significant but heterogeneous. These findings support routine cognitive assessment, harmonised endpoints, and prospective therapy-specific follow-up. PRECISE-ACTION is proposed as a preliminary, hypothesis-generating transdisciplinary framework for structured cognitive assessment, longitudinal tracking, integrated care, and future research.</p><p><strong>Registration: </strong>Open Science Framework (OSF), 2nbeh.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105002","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":"Proton Pump Inhibitor Co-prescription, Dabigatran Use, and Ischaemic Stroke or Transient Ischaemic Attack in Atrial Fibrillation: A Population-Based Case-Control Study.","authors":"Karim M Mahawish, Valery Feigin, Harvey White, Rita Krishnamurthi","doi":"10.1007/s40261-026-01600-9","DOIUrl":"https://doi.org/10.1007/s40261-026-01600-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Proton pump inhibitors (PPIs) reduce gastric acidity and lower dabigatran plasma concentrations, raising concern about a clinically relevant drug-drug interaction. We examined whether PPI co-prescription modified the association between dabigatran use and atrial fibrillation (AF)-associated ischaemic stroke (IS) or transient ischaemic attack (TIA).</p><p><strong>Methods: </strong>We conducted a population-based case-control study of adults with AF in Auckland, New Zealand. Cases were patients with adjudicated IS/TIA between September 2020 and August 2021 identified from the fifth Auckland Regional Community Stroke Study, which uses multiple overlapping ascertainment sources and independent clinical adjudication. Controls were patients with AF from the same source population who remained free of IS/TIA during the surveillance period, sampled from the Ministry of Health National Minimum Dataset. Individual-level demographics, comorbidities and medication exposures were obtained from electronic clinical records and dispensing data. Multivariable logistic regression included dabigatran use, PPI use and their interaction term, with adjustment for pre-specified clinical covariates.</p><p><strong>Results: </strong>The analytic sample comprised 300 IS/TIA cases and 1,608 controls. Dabigatran use was associated with lower odds of IS/TIA (adjusted odds ratio [aOR] 0.36 [95%CI 0.24-0.53]). PPI use was associated with higher odds of IS/TIA (aOR 1.55 [95%CI 1.08-2.24]), but this association is likely subject to residual confounding and should not be interpreted as causal. The dabigatran × PPI interaction was not statistically significant (aOR 0.98 [95%CI 0.57-1.69]; p = 0.94).</p><p><strong>Conclusion: </strong>We found no evidence of a large dabigatran-specific interaction with PPI co-prescription. These findings do not support a major clinically important attenuation of dabigatran's association with lower odds of AF-associated IS/TIA, although modest effect modification cannot be excluded. Generalisability to lower-risk primary-care AF populations and healthcare systems with different patient characteristics may be limited.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104982","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":"Serotonergic Toxicity and Hyponatremia Associated with Antidepressant Therapy: The Pivotal Role of SIADH.","authors":"Donato Morena, Matteo Lippi, Letizia Biso, Federico Lucci, Emanuela Turillazzi, Vittorio Fineschi, Pasquale Scognamiglio","doi":"10.1007/s40261-026-01599-z","DOIUrl":"https://doi.org/10.1007/s40261-026-01599-z","url":null,"abstract":"<p><p>Serotonin syndrome (SS) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) are well-recognized adverse drug reactions (ADRs) associated with serotonergic agents, particularly antidepressants. Although traditionally regarded as distinct clinical entities, accumulating evidence suggests that SIADH may represent a key pathophysiological link between serotonergic toxicity and acute hyponatremia, thereby explaining their frequent clinical overlap and, in some cases, severe or fatal outcomes. Excessive serotonergic activity can stimulate hypothalamic pathways regulating arginine vasopressin secretion, resulting in euvolemic hyponatremia and hyponatremic encephalopathy while simultaneously producing the characteristic neuromuscular, autonomic, and mental status abnormalities of SS. This narrative review examines the shared pathophysiological mechanisms, clinical manifestations, diagnostic challenges, and therapeutic implications of SS and SIADH-associated hyponatremia. A comprehensive literature search was conducted, including reviews, pharmacological studies, and case reports involving antidepressants, opioids, antihistamines, nutraceuticals, and emerging serotonergic agents such as ketamine, esketamine, and psilocybin. Particular attention is given to medication combinations, over-the-counter medications, and dietary supplements that may increase serotonergic burden through pharmacodynamic and pharmacokinetic interactions. The review highlights SIADH as the \"thin red line\" connecting serotonergic excess with rapid-onset hyponatremia and emphasizes the diagnostic complexity arising from the overlap between neurological manifestations of SS and metabolic encephalopathy secondary to hyponatremia. It also underscores the importance of a systematic diagnostic evaluation of suspected SIADH, including assessment of serum and urinary osmolality and urinary sodium concentration. In published case reports, the absence of urinary osmolality measurements frequently precludes confirmation of SIADH according to established diagnostic criteria, limiting the diagnosis to a possible or probable form rather than a definitive one. Greater awareness of this pathophysiological interplay is essential for early recognition, accurate differential diagnosis, risk stratification, and prevention of severe outcomes through careful medication review, appropriate laboratory evaluation, electrolyte monitoring, and prompt discontinuation of offending agents.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105008","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":"Cost Effectiveness of Teriparatide for Postmenopausal Osteoporosis: A Systematic Review.","authors":"Mohammad Alimoradnori, Ali Abutorabi, Mozhdeh Zabihiyeganeh, Jalal Arabloo, Reza Jahanghiri","doi":"10.1007/s40261-026-01586-4","DOIUrl":"10.1007/s40261-026-01586-4","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal osteoporosis is a major public health concern, imposing a substantial economic burden on healthcare systems. Teriparatide is one of the key pharmacological treatments; however, its cost effectiveness remains controversial.</p><p><strong>Objective: </strong>This systematic review aimed to evaluate the cost effectiveness of teriparatide in the treatment of postmenopausal women with osteoporosis.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in PubMed, Scopus, Embase, and Web of Science up to October 2024. The included studies comprised cost-effectiveness and cost-utility analyses conducted from healthcare system/payer and societal perspectives. Studies that met the inclusion criteria were assessed using the Quality of Health Economic Studies (QHES) checklist.</p><p><strong>Results: </strong>A total of 22 economic evaluations were included. Most studies found that teriparatide was not cost effective under general conditions, except in specific scenarios such as reduced drug prices, the use of generic alternatives, or under sensitivity analysis assumptions. The variability in willingness-to-pay thresholds and regional drug costs contributed substantially to differing incremental cost-effectiveness ratio outcomes across countries. Only a few studies accounted for indirect costs, and the limited geographic distribution highlighted the need for research in underrepresented regions such as the Middle East and Africa. Furthermore, a funding disclosure analysis suggested a potential bias in industry-sponsored studies, although no definitive conclusions could be drawn.</p><p><strong>Conclusions: </strong>Our findings suggest that teriparatide is generally not cost effective for the treatment of postmenopausal osteoporosis, although its economic value may vary depending on contextual and policy-related factors. Further robust economic evaluations are needed, incorporating both direct and indirect costs, and covering understudied regions. The findings of this review can support informed resource allocation and policy making in osteoporosis management. Limitations include heterogeneity across the included studies, potential language bias due to the inclusion of only English-language publications, and methodological variations that limited cross-study comparability.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1067-1103"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697180","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":"Risk of Neurological Adverse Events Between PD-L1 and PD-1 Inhibitors in South Korean Patients with Lung Cancer: A Target Trial Emulation Framework.","authors":"Sang Hee Kim, Seung Hyeun Lee, Sukhyang Lee, Sun-Young Chang, Ha-Lim Jeon, Hankil Lee","doi":"10.1007/s40261-026-01584-6","DOIUrl":"10.1007/s40261-026-01584-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Differences in programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors may influence their impacts on immune responses and result in distinct patterns of neurological adverse events (NAEs), which are uncommon but clinically significant. Therefore, we aimed to compare the risk of NAEs between PD-1 and PD-L1 inhibitors.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using a target trial emulation framework with nationwide data of patients with newly diagnosed lung cancer. Propensity score matching was used to minimize baseline differences. A multivariate competing risk hazard model was used to assess NAE incidence. Kaplan-Meier curves and Mann-Whitney U were used to depict cumulative incidence and evaluate time to onset, respectively.</p><p><strong>Results: </strong>Among the 931 patients per group, peripheral NAEs were more frequent with PD-L1 inhibitors (19.2% vs 14.1%), with a higher incidence density (23.91 vs 17.04 cases per 100 person-years). Within 30 days, NAEs were approximately three times more common with PD-1 inhibitors; however, beyond 360 days, the risk was higher with PD-L1 inhibitors (hazard ratio 1.83, p < 0.05). NAEs were more frequent with PD-L1 inhibitors in patients who had received prior chemotherapy (p < 0.05) and metastasis (p < 0.05). The median time to onset was similar between the two groups (141 vs 138 days, p = 0.69).</p><p><strong>Conclusions: </strong>To our knowledge, this study is one of the first studies to directly compare NAE risk between PD-L1 and PD-1 inhibitors using real-world data from South Korean patients with lung cancer. Given the expanding global use of immune checkpoint inhibitors, it offers valuable evidence for guiding future treatment strategies.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1137-1150"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599584","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":"Modeling Cancer Outcomes and Economic Impact of the Anti-PD-1/PD-L1 Immunotherapy in the Gulf: United Arab Emirates, Oman, and Kuwait.","authors":"Humaid O Al-Shamsi, Mohamed Farghaly, Ammar Abdaljalil, Abdulwahab Al-Tourah, Chana Saad, Youmna Bassil, Ghadah Albassam, Rami Nimer, Monika Naroz, Omar El-Badry, Rony Akel","doi":"10.1007/s40261-026-01577-5","DOIUrl":"10.1007/s40261-026-01577-5","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cancer has a substantial health and economic impact on the populations of the Gulf countries-the United Arab Emirates (UAE), Kuwait, and Oman; however, uncertainty remains among decision-makers, payers, and stakeholders regarding their clinical and economic advantages. Hence, this study aims to evaluate the potential health and economic impact of programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitor immunotherapies to reduce uncertainty and inform coverage, reimbursement, and treatment decisions across the Gulf region.</p><p><strong>Methods: </strong>The Health Impact Projection (HIP) model, a partitioned survival model, was adapted from a payer perspective for the UAE, Oman, and Kuwait to explore the health and economic impact of the anti-PD-1/PD-L1 class over 2022-2026 among key indications, including: first line non-squamous non-small cell lung cancer (1LNSCLC), neo-adjuvant triple-negative breast cancer (TNBC), metastatic TNBC, head and neck cancer, 1L metastatic urothelial carcinoma, metastatic renal cell carcinoma (RCC), second line endometrial cancer, 1L cervical cancer, and colorectal cancer. The model adopted a 1-to-5-year time horizon, structured in weekly cycles, with a new cohort joining yearly. Model inputs were based on publicly available data, literature, and expert advice.</p><p><strong>Results: </strong>The model estimated that, over 5 years, 3763 patients across the UAE, Kuwait, and Oman would receive anti-PD-1/PD-L1s treatments, resulting in total gains of 1745 life years, 2791 progression-free survival (PFS) years, and 1625 quality adjusted life-years (QALYs). The introduction of anti-PD-1/PD-L1s would have an average annual impact of $149 million and a 0.17% share of healthcare expenditure in 2022. While disease management and drug acquisition costs are significant, they are partly offset by reductions in end-of-life costs ($1,011,773/year) and cancer-related productivity losses ($3,111,454/year).</p><p><strong>Conclusions: </strong>The HIP model aids horizon scanning by providing a framework for stakeholder discussions on equitable access to anti-PD-1/PD-L1 treatments. It highlights the notable survival and QoL benefits of this novel class in Gulf countries, achievable with a modest 0.17% increase in healthcare expenditure.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1175-1185"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721118","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":"Signals of Venous Thromboembolism Risk from Drug-Drug Interactions Involving Benzodiazepines and Other Sedative Hypnotics: Self-Controlled Case Series Analyses.","authors":"Fengge Wang, Lin-Chieh Meng, Kacie Bogar, Colleen M Brensinger, Warren B Bilker, Sascha Dublin, Todd E H Hecht, John R Horn, Daniela C Moga, Michael E Thase, Brian L VanderBeek, Charles E Leonard","doi":"10.1007/s40261-026-01582-8","DOIUrl":"10.1007/s40261-026-01582-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Benzodiazepines and sedative hypnotics such as zolpidem (\"z-drugs\") are commonly prescribed for anxiety and sleep disorders. Epidemiologic evidence links their use to increased risk of venous thromboembolism. We investigated venous thromboembolism risk among concomitant users of individual benzodiazepines/z-drugs (examined separately) with other prescription medications to generate data-driven hypotheses about drug interactions resulting in clinically meaningful harm to inform future etiologic studies of specific drug combinations.</p><p><strong>Methods: </strong>We conducted a series of self-controlled case series studies within a 50% random sample of US Medicaid and Medicare data. Each cohort comprised person-time exposed to a benzodiazepine/z-drug, dichotomized into focal versus referent periods based on concomitant drug use versus non-use. We used conditional Poisson regression to estimate incidence rate ratios for hospital or emergency department presentation for venous thromboembolism. We generated ratios of incidence rate ratios, leveraging negative control analyses of eye drop-concomitant drug pairs, to minimize confounding by indication for the concomitant drug. We used semi-Bayes shrinkage to minimize false positives.</p><p><strong>Results: </strong>Among 1590 self-controlled case series studies involving 8853 individuals with venous thromboembolism, 38 (2.4%) potential drug interaction signals were identified before calibration. After adjustment for multiple testing and negative control findings, five (0.3%) signals remained, involving gabapentin combined with eszopiclone, lorazepam, clonazepam, or alprazolam, and apixaban combined with diazepam (ratio of incidence rate ratio range: 1.92-3.57). Four (80%) involved concurrent use of gabapentin, a medication largely used to treat neuropathic pain.</p><p><strong>Conclusions: </strong>Most benzodiazepine/z-drug combinations conferred no increased venous thromboembolism risk. However, concurrent use of a benzodiazepine/z-drug with gabapentin may increase the relative rate of venous thromboembolism up to 3.5-fold. As this work was hypothesis generating, a future etiologic study should confirm this potential drug interaction.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1151-1160"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618000","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":"Operationalizing Single-Dose Long-Acting Lipoglycopeptides for Treatment of ABSSSI in a U.S. Community Hospital Emergency Department.","authors":"Cole Orlikowski, Nicholas Torney, Aleah Hunt, William Britton, Cynthia Nichols","doi":"10.1007/s40261-026-01585-5","DOIUrl":"10.1007/s40261-026-01585-5","url":null,"abstract":"<p><strong>Background and objectives: </strong>Long-acting lipoglycopeptides (LaLGPs) offer an alternative to standard intravenous (IV) antibiotics for treating acute bacterial skin and skin structure infections (ABSSSIs). In September 2024, Munson Medical Center (Traverse City, MI) implemented an emergency department (ED)-based dalbavancin protocol targeting stable patients with ABSSSI who would otherwise require short-stay hospital admission. This study evaluated the clinical outcomes, operational feasibility, and financial impact of implementing an ED-based LaLGP protocol for ABSSSI management.</p><p><strong>Methods: </strong>This single-center, quasi-experimental pre-post study was conducted at a community hospital ED in the USA. The pre-implementation group included patients admitted for ≤ 72 h with ABSSSI (July 2022-August 2024). The post-implementation group received 1500 mg of dalbavancin in the ED per protocol (September 2024-May 2025). The primary outcome was 30-day hospital admission for recurrent ABSSSI. Secondary outcomes included 30-day ED visits, new antibiotic prescriptions, and 72-h all-cause admission.</p><p><strong>Results: </strong>Of 215 patients screened, 67 were included (48 pre-implementation, 19 post-implementation). No significant differences were observed in 30-day recurrent ABSSSI hospitalizations (2.1% versus 10.5%; P = 0.192), ED visits (4.2% versus 10.5%; P = 0.317), new antibiotic prescriptions (27.1% versus 10.5%; P = 0.200), or 72-h all-cause admissions (0% versus 5.3%; P = 0.284). A model-based, assumption-dependent financial analysis estimated that the pathway avoided 36 inpatient days over the 8-month post-implementation period, corresponding to an estimated net positive financial margin of approximately $100,000 USD.</p><p><strong>Conclusions: </strong>An ED-based LaLGP protocol for ABSSSI management was feasible for selected clinically stable patients. Although some outcomes were numerically higher in the post-implementation group, the small sample size and low event rates limited definitive comparisons.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"1161-1174"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618853","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}