Clinical therapeutics最新文献

{"title":"Letter to the Editor Regarding “Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant”","authors":"Hinpetch Daungsupawong PhD , Viroj Wiwanitkit MD","doi":"10.1016/j.clinthera.2025.07.017","DOIUrl":"10.1016/j.clinthera.2025.07.017","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 125-126"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788457","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}

{"title":"The Dangers of Practicing Recreational Regulation of Medicinal Cannabis","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2025.12.008","DOIUrl":"10.1016/j.clinthera.2025.12.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Page 1"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846588","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}

{"title":"Evaluation of Colorectal Cancer Incidence in the United States From 2021 to 2024 Using a National Multi-Payer Claims Database","authors":"Mallik Greene PhD, DBA, BPharm ,&nbsp;Shrey Gohil PhD ,&nbsp;Brad Stieber MS ,&nbsp;A. Burak Ozbay PhD, MBA ,&nbsp;Jorge Zapatier MD ,&nbsp;Jemel Bingham MD ,&nbsp;Joseph W. LeMaster MD, MPH ,&nbsp;Igor Stukalin MD ,&nbsp;Joseph C. Anderson MD ,&nbsp;Jordan K. Karlitz MD","doi":"10.1016/j.clinthera.2025.10.006","DOIUrl":"10.1016/j.clinthera.2025.10.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Colorectal cancer (CRC) remains the second leading cause of cancer-related death in the U.S. This study aimed to evaluate national CRC incidence from 2021 to 2024 using a large, multi-payer claims database.</div></div><div><h3>Methods</h3><div>This retrospective, cross-sectional study used a national multi-payer claims database to estimate annual CRC incidence from 2021 to 2024. Adults aged 45 to 75 years were included if they had no history of CRC diagnosis from 2015 through the year prior to the given calendar year (2021, 2022, 2023, or 2024) and had at least 1 medical or pharmacy event in a 3-year window centered on that year. CRC incidence was defined as a new diagnosis claim during each study year. Annual incidence rates per 100,000 individuals were calculated and stratified by sociodemographic characteristics. Associations between CRC incidence status (new diagnosis vs. no diagnosis) and sociodemographic subgroups were assessed using Pearson’s chi-square tests.</div></div><div><h3>Findings</h3><div>From 2021 to 2024, CRC incidence declined from 136.9 to 115.9 per 100,000 among 145 to 161 million eligible individuals, with declines in those aged 50 to 64 (120.8–101.7) and 65 to 75 (203.6–162.5). In contrast, incidence among those aged 45 to 49 increased from 59.5 to 63.1 over the same period. Incidence remained higher in males than females (129.4 vs. 104.3 in 2024), and although it decreased, it remained highest among Black individuals (225.1–156.8). Medicare Advantage enrollees had the highest incidence throughout (276.8–214.0), while those with commercial insurance had one of the lowest (112.8–93.4). Regional differences narrowed from 2021 to 2024 across the Northeast, Midwest, South, and West; CRC incidence status remained significantly associated with region (Pearson’s chi-square <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Overall, CRC incidence declined from 2021 to 2024, though rising rates among adults aged 45 to 49 highlight a growing early-onset burden. Associations between CRC incidence status and age, sex, race/ethnicity, insurance type, and region were observed, suggesting disparities that may reflect underlying equity gaps in prevention.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 57-64"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596170","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}

{"title":"Smart Cannabis: A Prescription Digital Therapeutic Framework for Enhancing Medical Cannabis Care","authors":"Shaheen E. Lakhan MD, PhD, FAAN ,&nbsp;Brendan Driscoll BS","doi":"10.1016/j.clinthera.2025.12.002","DOIUrl":"10.1016/j.clinthera.2025.12.002","url":null,"abstract":"<div><div>Despite expanding legalization and therapeutic interest, medical cannabis remains contested, characterized by self-directed use, inconsistent product labeling, and minimal clinical oversight. Patients are often left to navigate strain selection, dosing, and administration without meaningful support from the healthcare system. This open-loop model poses significant risks, particularly for vulnerable populations, and fails to meet the safety, efficacy, and accountability standards expected of medical treatments. This commentary introduces a Smart Cannabis model that would integrate medical cannabis with smartphone-delivered prescription digital therapeutics (PDTs) to improve precision, safety, and therapeutic effectiveness. PDTs could offer real-time monitoring, personalized guidance, and data-driven feedback that could enhance cannabis efficacy by optimizing formulation, dosing, and timing based on individual response patterns. Further, PDTs have been leveraged to treat migraine, depression, insomnia, and PTSD, which offer synergies with cannabis treatment. When combined, cannabis and PDTs could form a closed-loop care system capable of fine-tuning treatment to maximize intended outcomes while minimizing risks. If implemented, this fusion may also generate real-world evidence to inform clinical guidelines, policy decisions, and product development. Massachusetts’s Medical Use of Marijuana Program, administered by the Cannabis Control Commission, offers a unique opportunity to pilot this approach, given its robust regulatory infrastructure, centralized patient registries, and history of innovation. Policy recommendations include launching Smart Cannabis pilot programs, improving product labeling standards, establishing bundled reimbursement models, and expanding clinician education. Smart Cannabis is not simply a technological upgrade; it is a necessary evolution in cannabinoid care, one that aligns with the principles of precision medicine and modern therapeutic governance.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 46-50"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800195","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}

{"title":"Cannabis Research, Policy, and Therapeutics—An International Quasi-Experiment in Cannabis Policy— Part 1 (2026)","authors":"Julie K. Johnson PhD,&nbsp;Graelyn Humiston MS,&nbsp;Alexander Colby MA","doi":"10.1016/j.clinthera.2025.12.005","DOIUrl":"10.1016/j.clinthera.2025.12.005","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 2-4"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877711","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}

{"title":"Assessing the Role of Cannabis in Managing Spasticity in Multiple Sclerosis: A Systematic Review and Meta-Analysis","authors":"Yazan AlHabil M.D. ,&nbsp;Liza Saadeddin ,&nbsp;Hana Ishkirat ,&nbsp;Mariam Alqam ,&nbsp;Obada Hossoon M.D. ,&nbsp;Seema Hameedi M.D. ,&nbsp;Hamzeh Yacoub M.D. ,&nbsp;Diana Yasin ,&nbsp;Anita Bahbah ,&nbsp;Majd Oweidat M.D. ,&nbsp;Hanadi Mosa","doi":"10.1016/j.clinthera.2025.07.009","DOIUrl":"10.1016/j.clinthera.2025.07.009","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) is a complex, heterogeneous disease, and its management remains challenging due to varying symptoms and patient responses to treatments. While injectable therapies like glatiramer acetate and beta-interferon are common, they have limitations such as side effects and varying efficacy. Cannabis has garnered attention as a potential alternative treatment, particularly for symptoms like spasticity and pain.</div></div><div><h3>Objective</h3><div>This study aims to evaluate the efficacy of cannabis-based therapies for managing MS-related spasticity.</div></div><div><h3>Methods</h3><div>Nine clinical trials involving 2544 MS patients were included, with studies conducted between 2003 and 2021 across multiple countries. Cannabinoid therapies studied included whole-plant extracts, oils, and smoked cannabis containing delta-9-tetrahydrocannabinol and/or cannabidiol. Spasticity was assessed using standardized scales, including the Ashworth scale (AS), visual analog scale, and numeric rating scale (NRS). Effect sizes were pooled using random or fixed effects models, and heterogeneity and publication bias were evaluated using <em>I</em>², Tau², and funnel plots.</div></div><div><h3>Results</h3><div>The overall meta-analysis revealed a standardized mean difference (MD) of 39.19 (95% CI: 34.32–44.05) in spasticity scores, indicating notable improvement post-treatment. Subgroup analyses showed a MD of 20.36 (95% CI: 20.35–20.37) for AS and 1.18 (95% CI: 1.16–1.21) for NRS. However, substantial heterogeneity (<em>I</em>² = 100% for overall and AS analyses; 91% for NRS) and asymmetry in funnel plots suggest possible publication bias and study variability. Short-term studies demonstrated modest changes (MD = 4.53, 95% CI: −0.06 to 9.12), while long-term studies yielded larger effects (MD = 75.81, 95% CI: 66.39–85.22). Adverse events were generally mild, including dizziness and dry mouth.</div></div><div><h3>Conclusion</h3><div>Cannabis-based therapies are associated with clinically meaningful improvements in MS-related spasticity, particularly over longer durations. Despite the promising findings, high heterogeneity and suspected bias necessitate caution. Further high-quality randomized trials with standardized protocols and comprehensive safety assessments are warranted to validate efficacy and long-term outcomes.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 13-21"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768445","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}

{"title":"Efficacy and safety of Monoclonal Antibodies in Malaria Protection and Prevention of Transmission: A Systematic Review","authors":"Kanika Verma PhD ,&nbsp;Richa Singhal PhD ,&nbsp;Anup Anvikar MBBS, MD ,&nbsp;Praveen Kumar Bharti PhD ,&nbsp;Nitika Nitika MBBS, MD","doi":"10.1016/j.clinthera.2025.11.006","DOIUrl":"10.1016/j.clinthera.2025.11.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Despite advances in malaria control, progress toward elimination has stalled. Monoclonal antibodies (mAbs) have the capacity to provide rapid, long-lasting protection after a single administration. In this systematic review, we aimed to evaluate the efficacy, safety, and pharmacokinetic profiles of antimalarial mAbs—CIS43LS, L9LS, MAM01, and TB31F.</div></div><div><h3>Methods</h3><div>We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting this review. PubMed was searched from inception to 5 October 2025 for studies assessing the pharmacokinetics, safety, and efficacy of antimalarial mAbs. Eligible studies included Phases I and II clinical trials involving human participants.</div></div><div><h3>Findings</h3><div>Seven studies (n = 776 participants) were included. CIS43LS and L9LS demonstrated dose-dependent protection against <em>Plasmodium falciparum</em> infection for up to 6 months. CIS43LS achieved protective efficacy of 75% to 88% at doses ≥10 mg/kg (intravenous), whereas L9LS showed efficacy of 66% to 77% following subcutaneous administration in Phase II trials. Both mAbs exhibited favorable safety profiles, with only grade 1 to 2 adverse events (local site reactions, headache, and fatigue) reported. Pharmacokinetic analyses revealed extended half-lives (CIS43LS: 56–80 days; L9LS: 46.1 days; MAM01: 71.1 days) supporting their potential for seasonal deployment. Phase I study of MAM01 demonstrated a favorable safety profile and dose-dependent pharmacokinetics. All participants in control group and 18 (of 22) participants in intervention arm developed parasitemia. One participant who had received 5 mg/kg (subcutaneous) and 3 who had received dose 40 mg/kg (intravenous) were protected and did not develop parasitemia. TB31F demonstrated transmission-reducing activity exceeding 80% at doses ≥1 mg/kg (intravenous and subcutaneous), sustained for up to 160 days after administration.</div></div><div><h3>Implications</h3><div>Antimalarial mAbs show promise as scalable tools for malaria prevention and transmission reduction. Subcutaneous delivery and prolonged protection enhance their feasibility for integration into the public health system for wider implementation in community settings. Further large-scale trials assessing long-term efficacy, operational feasibility, and cost-effectiveness in diverse settings, including children and pregnant women, are required and will govern the feasibility of its use in wider community settings.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 104-116"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755520","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}

{"title":"Ciprofol Injection Combined With 6 Cephalosporins During Simulated Y-site Mixing: A Physicochemical Compatibility Study for Perioperative Administration","authors":"Baoxia Fang BPharm ,&nbsp;Qipeng Liu BPharm ,&nbsp;Wenya Deng BPharm ,&nbsp;Xi Cheng MPharm ,&nbsp;Jinguo Yang MD ,&nbsp;Fuchao Chen PharmD","doi":"10.1016/j.clinthera.2025.11.012","DOIUrl":"10.1016/j.clinthera.2025.11.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Simultaneous administration of multiple drugs via Y-site infusion is a common practice during the perioperative period; however, in-line incompatibility remains a significant safety concern. Ciprofol injection, a novel intravenous anesthetic based on lipid emulsifiers, may exhibit compromised stability when co-administered with other medications. This study systematically evaluated the compatibility and stability of ciprofol injection with 6 commonly used cephalosporins (cefazolin, cefuroxime, cefradine, cefotaxime, ceftriaxone, and cefoperazone) during Y-site infusion to ensure the safe and rational use of perioperative intravenous therapies.</div></div><div><h3>Methods</h3><div>Ciprofol injection was mixed with clinically relevant concentrations of 6 cephalosporins in 0.9% sodium chloride or 5% glucose solution at a 1:1 volume ratio under ambient conditions (25 ± 1°C). Samples were collected at predetermined time points (0, 2, 4, 6, and 8 hours) for comprehensive evaluation of physical and chemical properties, including appearance, pH value, Zeta potential, particle size/polydispersity index (PDI), osmotic pressure, and relative percentage content changes of the mixtures.</div></div><div><h3>Findings</h3><div>Within an 8-hour period, no visible changes in the appearance of any drug mixture were observed. The pH values fluctuated within ±0.5, while the average particle size remained stable at (215 ± 10) nm with uniform particle size distribution (PDI = 0.12 ± 0.04). The Zeta potential and osmotic pressure values exhibited stability throughout the study period. The relative drug content was maintained between 95% and 105%. Microscopic imaging analysis showed that there was no aggregation of milk droplets or abnormal increase of particle size in the mixture.</div></div><div><h3>Implications</h3><div>Under conditions of room temperature, ciprofol injection demonstrated compatibility and stability when administered via Y-site infusion with 6 commonly used cephalosporins at clinical dosage concentrations for up to 8 hours. These findings provide valuable guidance for the safe and effective use of ciprofol in perioperative settings.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 95-103"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767369","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}

{"title":"Measuring State Cannabis Policy Design Variation for Research and Policy: A Bundles Approach","authors":"Daniel J. Mallinson PhD ,&nbsp;Lilliard E. Richardson Jr PhD","doi":"10.1016/j.clinthera.2025.07.027","DOIUrl":"10.1016/j.clinthera.2025.07.027","url":null,"abstract":"<div><div>For understanding how cannabis legalization in the American states has affected public health, it is important to consider how policies vary by state. This commentary presents a policy bundles approach to measuring state cannabis policy variation. Measured from 1994 to 2023, three bundles—pharmaceutical, permissive, and fiscal—capture 36 different characteristics of state medical and recreational cannabis laws. The pharmaceutical bundle captures characteristics treating cannabis like a regulated pharmaceutical. The permissive bundle those that treat it like an easily accessed over-the-counter product. Finally, the fiscal bundle captures ways that states raise revenue from cannabis. Furthermore, measures are available capturing either policies as adopted or as implemented, allowing researchers to better link policy effects to actual implementation. The commentary demonstrates the bundle measures using the state of Massachusetts and concludes with future directions for using these publicly available measures for health research.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 29-33"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945672","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}

{"title":"What is a “Cannabis User”?","authors":"Ruth Fisher PhD","doi":"10.1016/j.clinthera.2025.11.003","DOIUrl":"10.1016/j.clinthera.2025.11.003","url":null,"abstract":"<div><h3>Purpose</h3><div>The increasing legalization and use of cannabis necessitate robust, standardized methods for identifying and characterizing cannabis users in research and clinical settings. Variability in user demographics, consumption patterns, and product types complicates comparisons across studies, hindering the development of evidence-based policies and interventions. This commentary aims to highlight the need for urgent development and adoption of uniform methodologies to enhance the reliability and generalizability of cannabis-related research.</div></div><div><h3>Methods</h3><div>A review was conducted of correlational studies on outcomes associated with cannabis use to assess methods for identifying and characterizing cannabis users in study populations. Gaps in standardization were identified through comparisons of survey tools, self-report measures, health records, and biochemical assays. A review of existing frameworks for characterizing cannabis use was conducted.</div></div><div><h3>Findings</h3><div>Current methods lack consistency in defining key variables such as “occasional use” or “heavy use” (ranging from monthly to weekly to daily); they fail to capture sufficient nuance in cannabis use patterns, such as lifetime patterns of use, form (eg, flower, concentrate, edibles), dose, and content (eg, THC, CBD) of use; and they fail to identify cannabis users, due to self-report biases, lack of health codes for general cannabis use, and inaccuracies in biological tests. A standardized framework, including the development of validated, easy-to-administer surveys, together with the assurance that study participants are safe from repercussions associated with honestly reporting cannabis use, could address these issues.</div></div><div><h3>Implications</h3><div>Standardized methods would improve the comparability of cannabis research, enabling meta-analyses and longitudinal studies to inform public health strategies. Consistent user characterization could guide clinical practices, such as tailored interventions for dependence or therapeutic use. Policymakers would benefit from reliable data to shape regulations. There is an urgency for collaborative efforts to develop and adopt global standards for identifying and characterizing cannabis users.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"48 1","pages":"Pages 22-28"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687156","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}