Clinical therapeutics最新文献

{"title":"Xanomeline and Trospium Chloride","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.10.001","DOIUrl":"10.1016/j.clinthera.2024.10.001","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 938-939"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496505","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":"Pharmacokinetics and Pharmacodynamics of a Fixed-Dose Combination of Esomeprazole and Magnesium Hydroxide Compared to the Enteric-Coated Esomeprazole","authors":"Yoonjin Kim MD ,&nbsp;Sungyeun Bae MD ,&nbsp;Inseung Jeon PhD ,&nbsp;Jihoon Kwon MS ,&nbsp;Sung Hee Hong MS ,&nbsp;Na Young Kim MS ,&nbsp;Kyung-Sang Yu MD, PhD ,&nbsp;In-Jin Jang MD, PhD ,&nbsp;SeungHwan Lee MD, PhD","doi":"10.1016/j.clinthera.2024.08.006","DOIUrl":"10.1016/j.clinthera.2024.08.006","url":null,"abstract":"<div><h3>Purpose</h3><div>A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects.</div></div><div><h3>Methods</h3><div>A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs.</div></div><div><h3>Findings</h3><div>After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (<em>P</em> = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs.</div></div><div><h3>Implications</h3><div>The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties. ClinicalTrials.gov identifier: NCT04324905 (<span><span>https://classic.clinicaltrials.gov/ct2/show/NCT04324905</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 870-876"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281584","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":"Cost-Effectiveness of Zanubrutinib Versus Bendamustine and Rituximab in Patients With Untreated Chronic Lymphocytic Leukemia","authors":"Jing Nie PhD ,&nbsp;Lihui Liu MD ,&nbsp;Huina Wu MD ,&nbsp;Shan Yuan MD ,&nbsp;Ke Tang BS ,&nbsp;Jiyong Wu PhD","doi":"10.1016/j.clinthera.2024.08.016","DOIUrl":"10.1016/j.clinthera.2024.08.016","url":null,"abstract":"<div><h3>Purpose</h3><div>Zanubrutinib, a potent and specific irreversible Bruton's tyrosine kinase inhibitor, has proven to be effective in untreated chronic lymphocytic leukemia (CLL), whether used alone or in combination with other therapies. Here, we compared the cost-effectiveness of zanubrutinib with bendamustine-rituximab (R-bendamustine) to determine its effectiveness as the first-line treatment for Chinese patients with untreated CLL.</div></div><div><h3>Methods</h3><div>The evaluation utilized a partitioned survival model, constructed using TreeAge Pro 2011 software, incorporating data from SEQUOIA trial (NCT03336333). Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. In this analysis, the quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and lifetime cost were calculated from the Chinese health care system perspective. Sensitivity analyses, including 1-way analysis and probabilistic sensitivity analysis, were carried out to explore the uncertainty of the modeling results. Additionally, several scenario analyses, including different zanubrutinib price calculation and 20-year time horizon, were evaluated.</div></div><div><h3>Findings</h3><div>The findings revealed that zanubrutinib had an incremental cost-effectiveness ratio of $58,258.18 per additional QALYs gained compared with bendamustine-rituximab, with zanubrutinib being cost-effective only if its price was reduced by more than 30%. Research indicated that zanubrutinib achieved at least a 3.70% probability of cost-effectiveness at the threshold of $38,223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to the utility of progressed disease.</div></div><div><h3>Implications</h3><div>The study highlighted the importance of considering the cost-effectiveness of zanubrutinib at its current price point for patients with untreated CLL in China, emphasizing the need for further assessment and potential pricing adjustments to enhance its economic viability in clinical practice.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 877-882"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281580","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":"SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum","authors":"Frank G. Preston ,&nbsp;Matthew Anson ,&nbsp;David R. Riley ,&nbsp;Gema H. Ibarburu ,&nbsp;Alexander Henney ,&nbsp;Gregory Y.H. Lip ,&nbsp;Daniel J. Cuthbertson ,&nbsp;Uazman Alam ,&nbsp;Sizheng S. Zhao","doi":"10.1016/j.clinthera.2024.06.021","DOIUrl":"10.1016/j.clinthera.2024.06.021","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to evaluate the relative association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) with the incidence of gout in patients with type 2 diabetes (T2D) using real-world data.</div></div><div><h3>Methods</h3><div>We conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation.</div></div><div><h3>Findings</h3><div>Prior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], <em>P &lt;</em> 0<em>.</em>0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74–0.92], <em>P</em> &lt; 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], <em>P</em> &lt; 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], <em>P</em> &lt; 0.0001).</div></div><div><h3>Implications</h3><div>In this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 835-840"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Placebo-Controlled Trial of Leronlimab in Mild-To-Moderate COVID-19","authors":"Harish Seethamraju MD ,&nbsp;Otto O. Yang MD ,&nbsp;Richard Loftus MD ,&nbsp;Onyema Ogbuagu MD ,&nbsp;Daniel Sammartino MD ,&nbsp;Ali Mansour MD ,&nbsp;Jonah B. Sacha PhD ,&nbsp;Sohita Ojha PhD ,&nbsp;Scott G. Hansen PhD ,&nbsp;Arvin Cyrus Arman PhD ,&nbsp;Jacob P. Lalezari MD","doi":"10.1016/j.clinthera.2024.08.019","DOIUrl":"10.1016/j.clinthera.2024.08.019","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Early in the course of the SARS-CoV-2 pandemic it was hypothesised that host genetics played a role in the pathophysiology of COVID-19 including a suggestion that the CCR5-Δ32 mutation may be protective in SARS-CoV-2 infection. Leronlimab is an investigational CCR5-specific humanized IgG4 monoclonal antibody currently in development for HIV-1 infection. We aimed to explore the impact of leronlimab on the severity of disease symptoms among participants with mild-to-moderate COVID-19.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The TEMPEST trial was a randomized, double-blind, placebo-controlled study in participants with mild-to-moderate COVID-19. Participants were randomly assigned in a 2:1 ratio to receive subcutaneous leronlimab (700 mg) or placebo on days 0 and 7. The primary efficacy endpoint was assessed by change in total symptom score based on fever, myalgia, dyspnea, and cough, at end of treatment (day 14).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Overall, 84 participants were randomized and treated with leronlimab (n = 56) or placebo (n = 28). No difference was observed in change in total symptom score (&lt;em&gt;P&lt;/em&gt; = 0.8184) or other pre-specified secondary endpoints between treatments. However, in a &lt;em&gt;post hoc&lt;/em&gt; analysis, 50.0% of participants treated with leronlimab demonstrated improvements from baseline in National Early Warning Score 2 (NEWS2) at day 14, compared with 20·8% of participants in the placebo group (&lt;em&gt;post hoc; p&lt;/em&gt; = 0.0223). Among participants in this trial with mild-to-moderate COVID-19 adverse events rates were numerically but not statistically significantly lower in leronlimab participants (33.9%) compared with placebo participants (50.0%).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;div&gt;At the time the TEMPEST trial was designed although CCR5 was known to be implicated in COVID-19 disease severity the exact pathophysiology of SARS-CoV-2 infection was poorly understood. Today it is well accepted that SARS-CoV-2 infection in asymptomatic-to-mild cases is primarily characterized by viral replication, with a heightened immune response, accompanied by diminished viral replication in moderate-to-severe disease and a peak in inflammatory responses with excessive production of pro-inflammatory cytokines in critical disease. It is therefore perhaps not surprising that no differences between treatments were observed in the primary endpoint or in pre-specified secondary endpoints among participants with mild-to-moderate COVID-19. However, the results of the exploratory &lt;em&gt;post hoc&lt;/em&gt; analysis showing that participants in the leronlimab group had greater improvement in NEWS2 assessment compared to placebo provided a suggestion that leronlimab may be associated with a lower likelihood of people with mild-to-moderate COVID-19 progressing to more severe disease and needs to be confirmed in other appropriately designed clinical trials.&lt;/div&gt;&lt;div&gt;ClinicalTrials.gov number, NCT04343651 &lt;span&gt;&lt;span&gt;https://classi","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 891-899"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364678","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":"Extraglycemic Effects of SGLT2i/GLP1-ra: A Topic Update","authors":"Uazman Alam BSc, MPHe, FRCP, PhD","doi":"10.1016/j.clinthera.2024.10.005","DOIUrl":"10.1016/j.clinthera.2024.10.005","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 826-827"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544223","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":"Budget Impact Analysis of Dapagliflozin in Treating Patients With Heart Failure With Reduced Ejection Fraction From the Perspective of Malaysian Public Healthcare System","authors":"Yi Jing Tan MPharm, MSc ,&nbsp;Joo Zheng Low MSc ,&nbsp;Siew Chin Ong PhD","doi":"10.1016/j.clinthera.2024.08.008","DOIUrl":"10.1016/j.clinthera.2024.08.008","url":null,"abstract":"<div><h3>Purpose</h3><div>This is a budget impact analysis that compared the scenario of treating heart failure with reduced ejection fraction (HFrEF) using dapagliflozin plus standard of care (SoC) versus a scenario without dapagliflozin, from the perspective of Ministry of Health (MOH) Malaysia over a 5-year time horizon.</div></div><div><h3>Methods</h3><div>A Microsoft Excel-based cost calculator was developed for such comparison. The estimated size of eligible population, uptake rates for dapagliflozin, as well as costs related to drugs, clinical events, and adverse events were based on published data, official tariffs, and databases, and expert opinion. Clinical data from the DAPA-HF trial were used to inform efficacy and safety inputs (i.e., hospitalization for heart failure (hHF), cardiovascular death, and adverse events). Results were reported as total annual and cumulative costs (in 2023 Malaysian Ringgits [RM], United States Dollars [USD], and European Union Euros, [EUR]; with exchange rates of 1 USD = RM 4.40 and 1 EUR = RM 4.90]), as well as the number of clinical events. Sensitivity and scenario analyses were also conducted.</div></div><div><h3>Findings</h3><div>The base-case analysis estimated that over a five-year period, the adoption of dapagliflozin for HFrEF treatment would result in a cumulative cost-saving of RM 2.6 million (USD 0.6 million/EUR 0.5 million), representing a 0.3% reduction in costs, driven primarily by reduced expenditure on hHF. Moreover, dapagliflozin treatment would lead to 731 fewer hHF and 366 fewer cardiovascular deaths. Sensitivity and scenario analyses revealed that the results were most sensitive to assumptions regarding loop diuretic requirements and the cost of dapagliflozin. Although cost savings or a net-zero balance were projected for the first four years, an anticipated 2.5% annual increase in dapagliflozin uptake in the longer term would lead to additional costs for the MOH, starting from the fifth year.</div></div><div><h3>Implications</h3><div>Incorporating dapagliflozin into the SoC can improve health outcomes for HFrEF patients and may generate cost savings, potentially easing the economic strain of HFrEF management on Malaysia's public healthcare system in the short term. Nonetheless, a modest increase in budget should be anticipated as more patients gain access to the treatment over time.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages e1-e9"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250403","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":"Clinical Update on an Anti-Alzheimer Drug Candidate CT1812: A Sigma-2 Receptor Antagonist","authors":"Guramrit Kaur B.Pharm,&nbsp;Zahid Ahmad Dar M.Pharm,&nbsp;Ankit Bajpai M.Pharm,&nbsp;Ranjit Singh PhD,&nbsp;Ranju Bansal PhD","doi":"10.1016/j.clinthera.2024.08.013","DOIUrl":"10.1016/j.clinthera.2024.08.013","url":null,"abstract":"<div><h3>Purpose</h3><div>This review article summarizes the progress and latest findings related to the investigational drug candidate CT1812, which is currently in phase 2 clinical trials for Alzheimer's disease (AD). The article outlines the development of this promising molecule and provides insights into its mechanism of action as sigma-2 receptor (S2R) antagonist along with the positive outcomes of various clinical trials. Literature mentioning AD therapeutics that specifically target amyloid-beta (Aβ) oligomers is limited even though these oligomers are established as the most neurotoxic forms of the Aβ protein. This timely article highlights the potential of CT1812 as a breakthrough in AD therapeutics, providing a new avenue for addressing the neurotoxic forms of Aβ and advancing the field toward a potential cure for AD.</div></div><div><h3>Methods</h3><div>The literature includes articles searched from PubMed and Google Scholar along with a comprehensive discussion of all the clinical research trials undertaken for CT1812. The review includes 12 clinical trials; of the total citations identified, 10 have been used to support the results of published trials.</div></div><div><h3>Findings</h3><div>The positive outcomes in the multiple clinical trials conducted on CT1812 indicate the emergence of an effective and promising drug candidate for AD. The article mentions a gap in the literature regarding AD therapeutics specifically targeting Aβ oligomers, which reveals lack of established treatments addressing Aβ oligomers, making the novel approach of CT1812 noteworthy.</div></div><div><h3>Implications</h3><div>Clinical treatments available today provide symptomatic relief, however, any drug providing a potential cure for AD remains an unanswered question. S2Rs mediated oligomer binding in addition to synaptic toxicity suggest the potential usefulness of CT1812 in AD treatment. Efficacy and safety of CT1812 in further clinical trials could represent a significant advancement in the field, offering a potential treatment that goes beyond the symptomatic relief and aimed at addressing the core mechanisms associated with AD.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages e21-e28"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281579","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":"Effectiveness of Remimazolam on Preventing Adverse Reactions Caused by Carboprost Tromethamine During Cesarean Section.","authors":"Jianjun Fan, Zhiguo Zhang, Jie Wang, Dianwei Han, Yongbo Zhen, Jinpei Fan, Shuai Wang, Fei Wang","doi":"10.1016/j.clinthera.2024.09.020","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.020","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the effectiveness of remimazolam in preventing adverse reactions triggered by carboprost tromethamine during cesarean section procedures.</p><p><strong>Methods: </strong>A total of 200 parturients scheduled for cesarean sections at risk of postpartum hemorrhage in our hospital from October 2022 to July 2023 were included. The participants were assigned via random number table method to either a study group or a control group, resulting in 100 cases in each. All parturients received combined spinal and epidural anesthesia (CSEA) during cesarean section, followed by administration of carboprost tromethamine (250 µg) for preventing postpartum hemorrhage after childbirth. CSEA was performed with 1.8 to 2 mL of 0.5% bupivacaine and 7 to 10 mL of 2% lidocaine. The study group was given remimazolam via intravenous infusion at a rate of 0.3 mg/kg/h commencing at 1 minute prior to CSEA and concluding with a final dosage adjustment 20 minutes preceding the end of surgery, while the control group was given the same volume of saline within this time frame. Primary outcome measures were adverse reactions and sedative effects of the parturients.</p><p><strong>Findings: </strong>Nausea and vomiting were the only adverse reactions that exhibited significant differences between groups. The study group reported significantly fewer cases (32 cases) of nausea and vomiting when compared to the 48 cases observed in the control group. Moreover, the use of remimazolam appeared to alleviate the severity of nausea and vomiting, as evidenced by the significantly lower incidence of Grade III event and the higher risk of Grade I event in comparison with the control group (P < 0.05). The Apgar scores of newborns at birth and 5 minutes after birth were compared, and no statistically significant difference was found (P > 0.05). Parturients receiving remimazolam exhibited better effective sedation outcomes and were more satisfied with the treatment when compared with controls (P < 0.05). There were no significant differences in postpartum bleeding volume at 2 and 12 hours postpartum, as well as in the duration of postpartum bleeding between the two groups (P > 0.05).</p><p><strong>Implications: </strong>Intravenous administration of remimazolam effectively prevents adverse reactions induced by carboprost tromethamine during cesarean section performed under CSEA, thereby improving sedative effects.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567941","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":"Medical Cannabis Dosing Trajectories of Patients: Evidence From Sales Data.","authors":"Alexandra F Kritikos, Myfanwy Graham, Dominic Hodgkin, Rosalie Liccardo Pacula","doi":"10.1016/j.clinthera.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.004","url":null,"abstract":"<p><strong>Purpose: </strong>Medical cannabis use is rising with limited high-quality clinical trial data to guide dosing. This study relies on real-world, longitudinal medical cannabis purchase data to provide information on Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) dosing trends for patients with qualifying medical conditions.</p><p><strong>Methods: </strong>A retrospective study of purchases by 16,727 patients obtaining medical cannabis from dispensaries located in New York between 2016 and 2019, recorded in point-of-sale data. Group-based trajectory modeling was used to identify clusters of patients following similar progressions in dosing of THC and CBD over time. χ² tests were performed to identify which patient characteristics and qualifying medical conditions were associated with membership in each trajectory group.</p><p><strong>Findings: </strong>Six trajectory groups were identified that described different patterns in the THC and CBD doses that patients purchased over the whole time period. For THC, the majority of patients (62.6%) purchased a steady amount but at different levels: consistently low (4.1 mg) or moderate (7.4 mg). Three groups, representing 22.0% together, exhibited doses that either fluctuate or constantly increase over time (5-20 mg). A final group of patients (15.8%) exhibited constant decrease in dose from 11 to 5 mg. For CBD, the data show similar trajectories, but at the generally higher values (4-16 mg). Patients with chronic pain, neuropathy, and cancer were overrepresented in groups where higher doses of THC were purchased over time. Patients with epilepsy had a higher representation in groups with higher doses of CBD across time.</p><p><strong>Implications: </strong>Results suggest heterogeneous dosing patterns and trajectories in the use of medical cannabis by patients with different medical conditions.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380237","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}