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Effects of the Japanese Kampo Medicines Rikkunshito, Shakuyakukanzoto and Goreisan on Lenvatinib Plasma Concentrations in Japanese Patients with Thyroid Cancer. 日本汉方药立昆士、释骨坎佐和哥瑞散对日本甲状腺癌患者Lenvatinib血药浓度的影响。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2024-12-01 DOI: 10.1007/s40801-024-00467-6
Kazuma Fujita, Akifumi Suzuki, Mitsuji Nagahama, Kiminori Sugino, Chie Masaki, Koichi Ito, Masatomo Miura

Background: Kampo medicines are often used in Japan as therapy for the side effects induced by oral kinase inhibitors. However, the pharmacokinetic interactions between Kampo medicines and oral kinase inhibitors such as lenvatinib have not been studied.

Objective: We investigated the effects of Kampo medicines (rikkunshito, shakuyakukanzoto and goreisan) on the steady-state plasma trough concentration (C0) of lenvatinib in patients with thyroid cancer.

Methods: Thirty-nine patients receiving lenvatinib therapy at Ito Hospital between May 2015 and December 2019 were enrolled. The mean C0 of lenvatinib with Kampo medicine, at the same dose as before initiating Kampo medicines, was used.

Results: After the repeated administration of rikkunshito (n = 21), shakuyakukanzoto (n = 10) or goreisan (n = 8), the mean C0 of lenvatinib and the laboratory test values of patients did not change significantly. In contrast to rikkunshito, which alleviates emesis by enhancing gastric emptying, the C0 values of lenvatinib with a proton pump inhibitor (PPI) (n = 16) or histamine H2 receptor antagonist (H2RA) (n = 4) were significantly lower than the C0 values without a PPI or H2RA (P = 0.007). The mean (range) change rate of the C0 of lenvatinib with a PPI or H2RA versus without a PPI or H2RA was 88.6% (69.9-115%), and was significantly greater than the change rate for rikkunshito (P = 0.029). There was no significant difference between the C0 of lenvatinib with a prokinetic agent (n = 7) versus without a prokinetic agent (P = 0.365).

Conclusions: Although these Kampo medicines are reported to inhibit drug-metabolizing enzymes and drug transporters, the risk of drug interactions for patients receiving lenvatinib therapy is low. Patients should feel confident that they can receive Kampo medicines as supportive care for lenvatinib therapy without a risk of drug interactions that could affect treatment efficacy.

背景:在日本,汉布药常用于治疗口服激酶抑制剂引起的副作用。然而,汉布药与lenvatinib等口服激酶抑制剂之间的药代动力学相互作用尚未被研究。目的:探讨汉方药(利坤士、泻骨丸和哥瑞散)对甲状腺癌患者lenvatinib稳态血药谷浓度(C0)的影响。方法:纳入2015年5月至2019年12月在伊藤医院接受lenvatinib治疗的39例患者。使用lenvatinib与汉布药的平均C0,剂量与开始使用汉布药之前相同。结果:反复给药利昆士藤(n = 21)、释骨坎佐藤(n = 10)、葛瑞散(n = 8)后,lenvatinib的平均C0和实验室检测值无明显变化。与rikkunshito相比,lenvatinib联合质子泵抑制剂(PPI) (n = 16)或组胺H2受体拮抗剂(H2RA) (n = 4)的C0值显著低于未加PPI或H2RA的C0值(P = 0.007)。lenvatinib联合PPI或H2RA组与未联合PPI或H2RA组的C0平均(范围)变化率为88.6%(699 -115%),显著高于rikkunshito组的变化率(P = 0.029)。lenvatinib加促动力剂组(n = 7)与不加促动力剂组(P = 0.365)的C0无显著差异。结论:尽管据报道这些汉布药能抑制药物代谢酶和药物转运体,但接受lenvatinib治疗的患者发生药物相互作用的风险很低。患者应该有信心,他们可以接受汉布药作为lenvatinib治疗的支持治疗,而不会有影响治疗效果的药物相互作用的风险。
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引用次数: 0
Lipid-Lowering Efficiency and Safety of Alirocumab 300 mg Using a 2-mL Autoinjector Device in Real-World Practice: The MARS Study.
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2025-01-28 DOI: 10.1007/s40801-024-00471-w
Klaus G Parhofer, Peter Bramlage, Constanze Gries, Cornelia Harder, Christiane Look, W Dieter Paar, Ursula Rauch-Kröhnert

Background: Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 used for the reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk patients not reaching their LDL-C target. Recently, a 2-mL prefilled autoinjector has been developed to support the monthly 300-mg dosing regimen with a single-injection administration.

Methods and objectives: Monthly application of 300 mg AlirRocumab (Praluent®) using the 2-mL SYDNEY Device (MARS) is a non-interventional, open, prospective, multi-center cohort study conducted in Germany between 2021 and 2023 with an observational period of 12 weeks. Patients included had primary hypercholesterolemia (heterozygous familial or non-familial) or mixed dyslipidemia and confirmed vascular disease and other risk factors or confirmed familial heterozygous hypercholesterolemia. Primary objectives were to assess the effectiveness of the 2-mL SYDNEY autoinjector measured by the lipid-lowering effect of alirocumab and to document therapy satisfaction, patient adherence, and persistence. Secondary objectives were to assess safety (adverse events) and tolerability.

Results: A total of 146 patients were analyzed: 110 (75.3%) patients were proprotein convertase subtilisin kexin type 9 inhibitor naïve and 36 (24.7%) were pre-treated with a proprotein convertase subtilisin kexin type 9 inhibitor. Patient mean age was 65.6 years with a preponderance of male gender (59.6%). At 12 weeks, the LDL-C value had decreased by a median of 59.5 mg/dL (1.5 mmol/L) in naïve patients (median relative decrease: - 52.0%). In the pre-treated group, the LDL-C value remained mainly unchanged (median slight numerical relative increase: 1.6%). Treatment satisfaction was rated similarly in both groups with most patients being satisfied/very satisfied and rating the injection as effective, safe, and easy to handle. Twenty-three adverse events in 13 patients (8.0%) were documented. Three patients experienced one serious adverse event each; for five patients, an adverse drug reaction was observed, although none was serious. The occurrence of adverse events was similar in both groups.

Conclusions: Alirocumab 300 mg administered with the 2-mL SYDNEY autoinjector was safe and effective in lowering LDL-C after 12 weeks in a routine clinical setting in Germany. The treatment schedule was perceived to be beneficial with excellent device acceptance and satisfaction, potentially increasing patient adherence.

Clinical trial registration: Clinicaltrials.gov: NCT05129241.

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引用次数: 0
Medication Hazards and Outcome Patterns of Pediatric Drug-Associated Liver Injury in Taiwan: An Analysis of 1998-2017 Spontaneous Adverse Drug Reaction Reports. 台湾儿童药物相关性肝损伤的用药危害与转归模式:1998-2017年自发性药物不良反应报告分析
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2025-01-08 DOI: 10.1007/s40801-024-00475-6
Yu-Ting Huang, Yen-Ming Huang, Ni-Chung Lee, Ping-Ing Lee, Yunn-Fang Ho

Background and objectives: Accumulating pediatric efficacy and safety data on drug use is inherently challenging yet essential. This study aimed to analyze the frequency and compute the odds of pediatric drug-associated liver injury across age groups (early childhood, middle childhood, and adolescence) and therapeutic categories using adverse drug reactions (ADRs) reporting data spanning nearly two decades.

Methods: We analyzed the reports of suspected ADRs occurring in children and adolescents in the Taiwan National Adverse Drug Reaction Reporting System during the period from May 1998 until July 2017. Standardized Medical Dictionary for Regulatory Activities Queries were utilized to identify suspected hepatic ADRs. Outcome patterns across age groups were compared using the chi-squared test, and disproportionality analysis was employed to calculate reporting odds ratios (RORs) of hepatic versus nonhepatic reports.

Results: Among 16,673 reports, 484 (2.9%) were identified as suspected hepatic ADRs, involving 193 distinct drugs. The mean age of affected individuals was 8.2 years. Outcome types in adolescents were predominantly serious (91.8%). Antibacterials for systemic use (18.8%) and antiepileptics (8.7%) were the most frequently implicated therapeutic categories. Drugs with high ADR occurrence rates and significant RORs included oxacillin (5.2%; ROR: 12.07), methotrexate (4.1%; ROR: 9.07), and phenobarbital (2.7%; ROR: 5.04). Some medications exhibited higher ratios of used-versus-recommended doses, suggesting inappropriate dosing.

Conclusions: Pediatric drug-associated liver injury was not uncommon and may result in serious outcomes. This study underscores the need for heightened vigilance in administering certain high-risk drugs and attentiveness in proper dosing for children, including adolescents.

背景和目的:积累儿童药物使用的有效性和安全性数据本身就具有挑战性,但也是必不可少的。本研究旨在利用近20年的药物不良反应(adr)报告数据,分析不同年龄组(儿童早期、儿童中期和青少年)和治疗类别儿童药物相关肝损伤的发生频率和几率。​使用规范活动查询标准医学词典来识别可疑的肝脏不良反应。使用卡方检验比较各年龄组的结果模式,并使用歧化分析来计算肝脏与非肝脏报告的报告优势比(RORs)。结果:在16673例报告中,484例(2.9%)被鉴定为疑似肝脏不良反应,涉及193种不同的药物。受影响个体的平均年龄为8.2岁。青少年的结局类型主要是严重的(91.8%)。全身使用的抗菌药(18.8%)和抗癫痫药(8.7%)是最常涉及的治疗类别。不良反应发生率高且不良反应发生率显著的药物包括:奥西林(5.2%);ROR: 12.07),甲氨蝶呤(4.1%;ROR: 9.07),苯巴比妥(2.7%;ROR: 5.04)。一些药物的使用剂量比推荐剂量高,表明剂量不适当。结论:儿童药物相关性肝损伤并不罕见,可能导致严重的后果。这项研究强调需要在管理某些高风险药物时提高警惕,并注意儿童,包括青少年的适当剂量。
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引用次数: 0
Comparative Efficacy of Lenvatinib Plus Immunotherapy and Regorafenib Plus Immunotherapy After Lenvatinib Failure for Advanced Hepatocellular Carcinoma: A Retrospective Study. Lenvatinib治疗晚期肝细胞癌失败后Lenvatinib联合免疫治疗与Regorafenib联合免疫治疗的疗效比较:一项回顾性研究。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2025-01-20 DOI: 10.1007/s40801-024-00480-9
Zeyu Yu, Bin Leng, Ran You, Lingfeng Diao, Qingyu Xu, Guowen Yin

Background: The combination of regorafenib and immune checkpoint inhibitor (ICI) has been the most popular second-line systemic therapy for advanced hepatocellular carcinoma (HCC). However, considering the good anti-tumor performance of lenvatinib, combined immunotherapy on the basis of lenvatinib after first-line lenvatinib failure is also popular in clinical practice. This study aimed to compare the efficacy and safety of regorafenib plus ICI (TACE-R-I) versus lenvatinib plus ICI (TACE-L-I) in patients with advanced HCC after lenvatinib failure.

Methods: In this single-center retrospective study, 164 patients with advanced HCC were enrolled from January 2019 to March 2024 in China. All patients were aged ≥ 18 years, clinically or pathologically diagnosed with HCC. All patients received trans-arterial chemoembolization (TACE) as local treatment. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were compared between groups. The Cox regression model was used to analyze the factors associated with OS and PFS.

Results: We compared 77 patients from each group after propensity score matching (PSM). There was no significant difference in the OS (p = 0.255) or PFS (p = 0.387) between groups. However, in the subgroup (distant metastases, Barcelona Clinic Liver Cancer (BCLC) stage C or tumor thrombus), the TACE-R-I group showed better survival benefit than the TACE-L-I group. The multivariable Cox regression model suggested that BCLC stage and alpha-fetoprotein (AFP) were independently associated with OS. Distant metastases, tumor thrombus and Child-Pugh were independent associated factors for PFS (p < 0.05). The frequency of grade ≥ 3 TRAEs was not significantly different between groups (p ≥ 0.05).

Conclusion: Our study demonstrated that in patients with greater tumor burden, the TACE-R-I group showed better OS and PFS benefits than the TACE-L-I group. However, in the overall population of HCC patients, there was no significant difference in efficacy and safety between the groups.

背景:瑞非尼联合免疫检查点抑制剂(ICI)已成为晚期肝细胞癌(HCC)最流行的二线全身治疗。然而,考虑到lenvatinib良好的抗肿瘤性能,在一线lenvatinib失败后,在lenvatinib的基础上联合免疫治疗在临床中也很流行。本研究旨在比较reorafenib + ICI (TACE-R-I)与lenvatinib + ICI (TACE-L-I)在lenvatinib失效后晚期HCC患者中的疗效和安全性。方法:在这项单中心回顾性研究中,于2019年1月至2024年3月在中国招募了164例晚期HCC患者。所有患者年龄≥18岁,临床或病理诊断为HCC。所有患者均接受经动脉化疗栓塞(TACE)作为局部治疗。比较两组患者的总生存期(OS)、无进展生存期(PFS)和治疗相关不良事件(TRAEs)。采用Cox回归模型分析影响OS和PFS的相关因素。结果:经倾向评分匹配(PSM)后,两组共77例患者进行比较。两组间OS (p = 0.255)和PFS (p = 0.387)差异无统计学意义。然而,在亚组(远处转移,巴塞罗那临床肝癌(BCLC) C期或肿瘤血栓)中,TACE-R-I组的生存获益优于TACE-L-I组。多变量Cox回归模型提示BCLC分期和甲胎蛋白(AFP)与OS独立相关。远处转移、肿瘤血栓和Child-Pugh是PFS的独立相关因素(p结论:我们的研究表明,在肿瘤负担较大的患者中,TACE-R-I组比TACE-L-I组具有更好的OS和PFS益处。然而,在HCC患者的总体人群中,两组之间的疗效和安全性没有显著差异。
{"title":"Comparative Efficacy of Lenvatinib Plus Immunotherapy and Regorafenib Plus Immunotherapy After Lenvatinib Failure for Advanced Hepatocellular Carcinoma: A Retrospective Study.","authors":"Zeyu Yu, Bin Leng, Ran You, Lingfeng Diao, Qingyu Xu, Guowen Yin","doi":"10.1007/s40801-024-00480-9","DOIUrl":"10.1007/s40801-024-00480-9","url":null,"abstract":"<p><strong>Background: </strong>The combination of regorafenib and immune checkpoint inhibitor (ICI) has been the most popular second-line systemic therapy for advanced hepatocellular carcinoma (HCC). However, considering the good anti-tumor performance of lenvatinib, combined immunotherapy on the basis of lenvatinib after first-line lenvatinib failure is also popular in clinical practice. This study aimed to compare the efficacy and safety of regorafenib plus ICI (TACE-R-I) versus lenvatinib plus ICI (TACE-L-I) in patients with advanced HCC after lenvatinib failure.</p><p><strong>Methods: </strong>In this single-center retrospective study, 164 patients with advanced HCC were enrolled from January 2019 to March 2024 in China. All patients were aged ≥ 18 years, clinically or pathologically diagnosed with HCC. All patients received trans-arterial chemoembolization (TACE) as local treatment. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were compared between groups. The Cox regression model was used to analyze the factors associated with OS and PFS.</p><p><strong>Results: </strong>We compared 77 patients from each group after propensity score matching (PSM). There was no significant difference in the OS (p = 0.255) or PFS (p = 0.387) between groups. However, in the subgroup (distant metastases, Barcelona Clinic Liver Cancer (BCLC) stage C or tumor thrombus), the TACE-R-I group showed better survival benefit than the TACE-L-I group. The multivariable Cox regression model suggested that BCLC stage and alpha-fetoprotein (AFP) were independently associated with OS. Distant metastases, tumor thrombus and Child-Pugh were independent associated factors for PFS (p < 0.05). The frequency of grade ≥ 3 TRAEs was not significantly different between groups (p ≥ 0.05).</p><p><strong>Conclusion: </strong>Our study demonstrated that in patients with greater tumor burden, the TACE-R-I group showed better OS and PFS benefits than the TACE-L-I group. However, in the overall population of HCC patients, there was no significant difference in efficacy and safety between the groups.</p>","PeriodicalId":11282,"journal":{"name":"Drugs - Real World Outcomes","volume":" ","pages":"135-143"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patients' Health-Related Quality of Life and Use of Medicinal Cannabis: A Cross-Sectional Survey Study. 患者健康相关生活质量与药用大麻的使用:一项横断面调查研究
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2025-01-10 DOI: 10.1007/s40801-024-00479-2
Frederik Rosenbæk, Sonja Wehberg, Line Bjørnskov Pedersen, Jesper Bo Nielsen, Jens Søndergaard

Background: Studies on medicinal cannabis (MC) have primarily investigated effects on diseases and symptoms, while there is only sparse knowledge on patients' health-related quality of life. Our aim was, firstly, to compare the health-related quality of life of patients (MC users and non-users) within four specified diagnostic indications (multiple sclerosis, paraplegia, neuropathy, and nausea and vomiting after chemotherapy) with that of patients with other diagnostic indications (MC users only) and the adult population (non-users only). Secondly, we estimate the associations between use of MC and health-related quality of life for patients in the four specified diagnostic indications.

Methods: We collected data on quality-adjusted life years (QALYs), using EQ-5D-3L, and patients' self-reported use of MC in a Danish nationwide online survey distributed to 23,846 patients in October 2020. We compared QALY scores of all groups using a two-tailed t-test, listed QALY scores of MC users versus non-users, and investigated associations between QALY score and MC use using unadjusted and adjusted linear regression analyses. Significance level was set to p-value < 0.05.

Results: A total of 9265 patients took part in the survey. All diagnostic indications had a statistically significant lower QALY score than the adult population (0.87). Paraplegia patients had the lowest QALY score, being 0.36 lower, followed by other diagnostic indication (- 0.34), multiple sclerosis (- 0.20), neuropathy (- 0.13), and nausea and vomiting after chemotherapy (- 0.06). MC users had a statistically significant lower QALY score than non-users (0.44 vs 0.74). Users redeeming 1-6 and ≥ 7 MC prescriptions (except for paraplegia patients) had a statistically significant lower QALY score than non-users, ranging between 0.11-0.24 and 0.26-0.32 lower than non-users, accordingly. Although, it should be noted that the number of users was small when stratifying by number of prescriptions.

Conclusion: Patients with either multiple sclerosis, paraplegia, neuropathy, or nausea and vomiting after chemotherapy had a significantly lower health-related quality of life than individuals from the adult population. Users of medicinal cannabis also had a significantly lower health-related quality of life compared with non-users, in all diagnostic indications.

背景:药用大麻(MC)的研究主要是调查对疾病和症状的影响,而对患者健康相关生活质量的了解很少。首先,我们的目的是比较四种特定诊断指征(多发性硬化症、截瘫、神经病变和化疗后恶心呕吐)内患者(MC使用者和非使用者)与其他诊断指征(仅MC使用者)和成人(仅非使用者)的健康相关生活质量。其次,我们估计在四种特定的诊断指征中使用MC与患者健康相关的生活质量之间的关联。方法:我们使用EQ-5D-3L收集了质量调整生命年(QALYs)的数据,并在2020年10月对23,846名患者进行的丹麦全国在线调查中收集了患者自我报告的MC使用情况。我们使用双尾t检验比较了所有组的QALY得分,列出了MC使用者与非使用者的QALY得分,并使用未调整和调整的线性回归分析调查了QALY得分与MC使用之间的关系。结果:共有9265例患者参与了调查。所有诊断指征的QALY评分均低于成人(0.87)。截瘫患者的QALY评分最低,为0.36,其次是其他诊断指征(- 0.34)、多发性硬化症(- 0.20)、神经病变(- 0.13)和化疗后恶心呕吐(- 0.06)。MC使用者的QALY评分低于非使用者(0.44 vs 0.74)。使用1-6张、≥7张MC处方者(截瘫患者除外)的QALY评分低于非使用者,分别为0.11-0.24、0.26-0.32,差异有统计学意义。但需要注意的是,按处方数量分层时,使用人数较少。结论:化疗后伴有多发性硬化症、截瘫、神经病变或恶心和呕吐的患者的健康相关生活质量明显低于成人。在所有诊断指征中,医用大麻使用者的健康相关生活质量也明显低于非使用者。
{"title":"Patients' Health-Related Quality of Life and Use of Medicinal Cannabis: A Cross-Sectional Survey Study.","authors":"Frederik Rosenbæk, Sonja Wehberg, Line Bjørnskov Pedersen, Jesper Bo Nielsen, Jens Søndergaard","doi":"10.1007/s40801-024-00479-2","DOIUrl":"10.1007/s40801-024-00479-2","url":null,"abstract":"<p><strong>Background: </strong>Studies on medicinal cannabis (MC) have primarily investigated effects on diseases and symptoms, while there is only sparse knowledge on patients' health-related quality of life. Our aim was, firstly, to compare the health-related quality of life of patients (MC users and non-users) within four specified diagnostic indications (multiple sclerosis, paraplegia, neuropathy, and nausea and vomiting after chemotherapy) with that of patients with other diagnostic indications (MC users only) and the adult population (non-users only). Secondly, we estimate the associations between use of MC and health-related quality of life for patients in the four specified diagnostic indications.</p><p><strong>Methods: </strong>We collected data on quality-adjusted life years (QALYs), using EQ-5D-3L, and patients' self-reported use of MC in a Danish nationwide online survey distributed to 23,846 patients in October 2020. We compared QALY scores of all groups using a two-tailed t-test, listed QALY scores of MC users versus non-users, and investigated associations between QALY score and MC use using unadjusted and adjusted linear regression analyses. Significance level was set to p-value < 0.05.</p><p><strong>Results: </strong>A total of 9265 patients took part in the survey. All diagnostic indications had a statistically significant lower QALY score than the adult population (0.87). Paraplegia patients had the lowest QALY score, being 0.36 lower, followed by other diagnostic indication (- 0.34), multiple sclerosis (- 0.20), neuropathy (- 0.13), and nausea and vomiting after chemotherapy (- 0.06). MC users had a statistically significant lower QALY score than non-users (0.44 vs 0.74). Users redeeming 1-6 and ≥ 7 MC prescriptions (except for paraplegia patients) had a statistically significant lower QALY score than non-users, ranging between 0.11-0.24 and 0.26-0.32 lower than non-users, accordingly. Although, it should be noted that the number of users was small when stratifying by number of prescriptions.</p><p><strong>Conclusion: </strong>Patients with either multiple sclerosis, paraplegia, neuropathy, or nausea and vomiting after chemotherapy had a significantly lower health-related quality of life than individuals from the adult population. Users of medicinal cannabis also had a significantly lower health-related quality of life compared with non-users, in all diagnostic indications.</p>","PeriodicalId":11282,"journal":{"name":"Drugs - Real World Outcomes","volume":" ","pages":"125-133"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and Effectiveness of Brigatinib in Anaplastic Lymphoma Kinase (ALK) Positive Metastatic Non-Small Cell Lung Cancer (NSCLC) in Argentina: A Post-Marketing Surveillance Study.
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-26 DOI: 10.1007/s40801-025-00484-z
Claudio Martin, Gabriela Ileana Malcervelli, Gastón Lucas Martinengo, Patricio Levit, Patricio Servienti, Elisa Malaver, Laura Brion, Vanesa Patronella, Andrea Zumárraga, Jose Zarba

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor was licensed for the treatment of ALK-positive metastatic non-small cell lung cancer in 2016. However, real-world evidence on the safety and effectiveness of brigatinib in Latin America remains limited.

Objective: The aim of this study was to assess the safety and effectiveness of brigatinib in the real world in Argentina.

Methods: We conducted a non-interventional cohort study of adult patients (aged ≥  18 years) with a diagnosis of ALK-positive metastatic non-small cell lung cancer not previously treated (first line) or previously treated (second line) with an ALK inhibitor and who received at least one dose of brigatinib between November 2020 and March 2023. The primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes at the 24-week follow-up were the percentage of patients with an overall best objective response rate of complete or partial response; intracranial objective response rate; progression-free survival; and overall survival.

Results: Of the 39 patients included in the study (n = 22 [first line]; n = 17 [second line]), 12 patients (30.7%) experienced treatment-emergent adverse events, with the most frequent being increased levels of transaminases (7.6%), increased level of blood creatine phosphokinase (5%) and hypokalaemia (5%). Most adverse events (85.7%) were mild to moderate. Effectiveness outcomes at 24 weeks in patients treated with brigatinib first line or second line, respectively, were as follows: overall objective response rate: 81.8% and 70.5%; intracranial objective response rate (in patients with brain metastases at baseline): 66.6% and 88.8%; progression-free survival: 93.8% and 82.4%; overall survival: 100% and 87.5%.

Conclusions: Brigatinib was demonstrated to be a safe and effective treatment option for ALK-positive metastatic non-small cell lung cancer in routine clinical practice in Argentina.

Clinical trial registration: NCT04887519.

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引用次数: 0
US Clinical Practice Experience with Eculizumab in Myasthenia Gravis: Acute Clinical Events and Healthcare Resource Utilization. 依库珠单抗治疗重症肌无力的美国临床实践经验:急性临床事件和医疗资源利用。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1007/s40801-024-00457-8
Richard J Nowak, Ali A Habib, Andrew J Klink, Srikanth Muppidi, Anju Parthan, S Chloe Sader, Alexandrina Balanean, Ajeet Gajra, James F Howard

Background and objective: The terminal complement inhibitor eculizumab is approved in the USA for the treatment of patients with acetylcholine receptor antibody-positive generalized myasthenia gravis (MG). The ELEVATE study aimed to examine clinical-practice outcome data on eculizumab effectiveness in US adults with MG (generalized or ocular). This paper reports the findings on MG exacerbations and crises and associated healthcare resource utilization, and the use of rescue therapy.

Methods: A retrospective chart review was conducted of US adults with MG who initiated eculizumab. Outcomes assessed for up to 2 years before and after eculizumab initiation included percentages and rates per patient per year (PPPY) of exacerbations and crises (the latter defined as intubation/impending intubation), healthcare resource utilization, and rescue therapy administration.

Results: A total of 119 patients diagnosed with MG were enrolled in the study; 92 patients had ≥ 3 months of data both before and during eculizumab therapy and were included in the analyses. The mean rate of MG exacerbations decreased from 0.385 PPPY before eculizumab initiation to 0.152 PPPY during eculizumab treatment (p = 0.0034); the mean rate of MG crises decreased from 0.411 to 0.056 PPPY (p = 0.0018). Rates of healthcare resource utilization and rescue therapy use also decreased significantly during eculizumab treatment.

Conclusions: This retrospective chart review analysis provides evidence for a beneficial impact of eculizumab treatment on the incidence of MG exacerbations and crises and associated healthcare resource utilization in clinical practice, and on rescue therapy use. These data further support the therapeutic benefits of eculizumab in patients with MG.

背景和目的:美国已批准使用终末补体抑制剂依库珠单抗治疗乙酰胆碱受体抗体阳性的全身性肌无力(MG)患者。ELEVATE 研究旨在检查依库珠单抗对美国成人 MG(全身型或眼型)患者的临床实践效果数据。本文报告了有关 MG 病情加重和危机、相关医疗资源使用情况以及抢救疗法使用情况的研究结果:方法:我们对开始使用依库珠单抗的美国成人 MG 患者进行了回顾性病历审查。方法:对使用依库珠单抗的美国成人 MG 患者进行了回顾性病历审查,评估了使用依库珠单抗前后长达 2 年的结果,包括病情加重和危象(后者定义为插管/即将插管)的百分比和年人均发病率(PPPY)、医疗资源使用情况以及抢救治疗的使用情况:共有119名确诊为MG的患者参与了研究,其中92名患者在接受依库珠单抗治疗前和治疗期间的数据均≥3个月,并纳入了分析。MG病情恶化的平均发生率从开始使用依库珠单抗前的0.385 PPPY降至依库珠单抗治疗期间的0.152 PPPY(p = 0.0034);MG危象的平均发生率从0.411 PPPY降至0.056 PPPY(p = 0.0018)。在依库珠单抗治疗期间,医疗资源利用率和抢救治疗使用率也显著下降:这项回顾性病历分析提供了证据,证明依库珠单抗治疗对MG加重和危象的发生率、临床实践中相关医疗资源的使用以及抢救治疗的使用产生了有益的影响。这些数据进一步证实了依库珠单抗对 MG 患者的治疗效果。
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引用次数: 0
A Pilot Study on the Collection of Adverse Event Data from the Patient Using an Electronic Platform in a Cancer Clinical Trial Unit. 癌症临床试验单位使用电子平台收集患者不良事件数据的试点研究。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-11-02 DOI: 10.1007/s40801-024-00461-y
Minna Grahvendy, Bena Brown, Laurelie R Wishart

Background and objective: Accurate and robust adverse event (AE) data collection is crucial in cancer clinical trials to ensure participant safety. Frameworks have been developed to facilitate the collection of AE data and now the traditional workflows are facing renewal to include patient-reported data, improving completeness of AE data. We explored one of these workflows in a cancer clinical trial unit.

Methods: The study was a single-site study conducted at a tertiary hospital located in Australia. Patients consenting to a clinical trial were eligible for inclusion in this study. Participants used an electronic platform-My Health My Way (MHMW)-to report their symptomatic data weekly for 24 weeks. A symptom list was included within the platform, along with a free text field. Data reported via the platform was compared with data recorded in the patient's medical chart. Time taken to compile data from each source was recorded, along with missing data points. Agreement between patient-reported data and data recorded in the medical notes was assessed using Kappa and Gwet's AC1; time taken to compile data and missing data points were assessed using a Wilcoxon signed rank test.

Results: Low agreement was found between patient- and clinician-reported data (- 0.482 and - 0.159 by Kappa and Gwet's AC1 respectively). Only 127 (30%) of the total 428 AEs were reported by both MHMW and medical notes. Patients reported higher rates of symptoms from the symptom list, while clinicians reported higher rates of symptoms outside of the symptom list. Time taken to compile the data from MHMW was significantly less than that taken to review medical notes (2.19 min versus 5.73 min respectively; P <  0.001). There were significantly less missing data points from the MHMW data compared with the medical notes (1.4 versus 7.8; P < 0.001).

Conclusions: This study confirms previous reports that patient- and clinician-reported adverse event data show low agreement. This study also shows that clinical trial sites could significantly reduce the work performed by research staff in the collection of adverse event data by implementing an electronic, patient-reported platform.

背景和目的:在癌症临床试验中,准确、可靠的不良事件(AE)数据收集对确保参与者的安全至关重要。为方便收集 AE 数据,人们开发了一些框架,现在传统的工作流程正面临更新,以纳入患者报告的数据,从而提高 AE 数据的完整性。我们在一个癌症临床试验单位探索了其中一个工作流程:本研究是在澳大利亚一家三级医院进行的单点研究。同意参加临床试验的患者有资格加入本研究。参与者使用电子平台 "我的健康我做主(MHMW)"报告症状数据,每周一次,持续24周。该平台包含一个症状列表和一个自由文本字段。通过平台报告的数据与患者病历中记录的数据进行比较。记录了从每个来源收集数据所需的时间以及缺失的数据点。使用 Kappa 和 Gwet's AC1 评估患者报告的数据与病历记录的数据之间的一致性;使用 Wilcoxon 签名秩检验评估整理数据所花费的时间和缺失的数据点:患者和临床医生报告的数据之间的一致性较低(根据 Kappa 和 Gwet's AC1 分别为 - 0.482 和 - 0.159)。在总共 428 例 AE 中,只有 127 例(30%)同时由 MHMW 和医疗记录报告。患者报告的症状清单中的症状比例较高,而临床医生报告的症状清单之外的症状比例较高。汇编 MHMW 数据所需的时间明显少于查阅病历所需的时间(分别为 2.19 分钟和 5.73 分钟;P 结论:本研究证实了之前的报告,即患者和临床医生报告的不良事件数据显示出较低的一致性。本研究还表明,临床试验机构可通过实施患者报告电子平台,大幅减少研究人员收集不良事件数据的工作量。
{"title":"A Pilot Study on the Collection of Adverse Event Data from the Patient Using an Electronic Platform in a Cancer Clinical Trial Unit.","authors":"Minna Grahvendy, Bena Brown, Laurelie R Wishart","doi":"10.1007/s40801-024-00461-y","DOIUrl":"10.1007/s40801-024-00461-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Accurate and robust adverse event (AE) data collection is crucial in cancer clinical trials to ensure participant safety. Frameworks have been developed to facilitate the collection of AE data and now the traditional workflows are facing renewal to include patient-reported data, improving completeness of AE data. We explored one of these workflows in a cancer clinical trial unit.</p><p><strong>Methods: </strong>The study was a single-site study conducted at a tertiary hospital located in Australia. Patients consenting to a clinical trial were eligible for inclusion in this study. Participants used an electronic platform-My Health My Way (MHMW)-to report their symptomatic data weekly for 24 weeks. A symptom list was included within the platform, along with a free text field. Data reported via the platform was compared with data recorded in the patient's medical chart. Time taken to compile data from each source was recorded, along with missing data points. Agreement between patient-reported data and data recorded in the medical notes was assessed using Kappa and Gwet's AC<sub>1</sub>; time taken to compile data and missing data points were assessed using a Wilcoxon signed rank test.</p><p><strong>Results: </strong>Low agreement was found between patient- and clinician-reported data (- 0.482 and - 0.159 by Kappa and Gwet's AC<sub>1</sub> respectively). Only 127 (30%) of the total 428 AEs were reported by both MHMW and medical notes. Patients reported higher rates of symptoms from the symptom list, while clinicians reported higher rates of symptoms outside of the symptom list. Time taken to compile the data from MHMW was significantly less than that taken to review medical notes (2.19 min versus 5.73 min respectively; P <  0.001). There were significantly less missing data points from the MHMW data compared with the medical notes (1.4 versus 7.8; P < 0.001).</p><p><strong>Conclusions: </strong>This study confirms previous reports that patient- and clinician-reported adverse event data show low agreement. This study also shows that clinical trial sites could significantly reduce the work performed by research staff in the collection of adverse event data by implementing an electronic, patient-reported platform.</p>","PeriodicalId":11282,"journal":{"name":"Drugs - Real World Outcomes","volume":" ","pages":"725-734"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Omeprazole and Risk of Hypertension: Analysis of Existing Literature and the WHO Global Pharmacovigilance Database. 奥美拉唑与高血压风险:现有文献和世界卫生组织全球药物警戒数据库分析》。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-06-22 DOI: 10.1007/s40801-024-00441-2
Merhawi Bahta, Natnael Russom, Amon Solomon Ghebrenegus, Yohana Tecleab Okubamichael, Mulugeta Russom

Introduction: The association between omeprazole and hypertension is poorly documented. The summary of product characteristics of omeprazole approved by major regulators did not mention hypertension as an adverse drug event. Triggered by a locally reported case, this study was conducted to assess the possible causal relationship between omeprazole and hypertension.

Methods: Globally reported cases of hypertension following use of omeprazole submitted to the World Health Organization global database, VigiBase, were retrieved on 5 March 2024 and analyzed descriptively. Besides this, a literature search was made to identify preclinical, clinical, and epidemiological information on the association between omeprazole and hypertension or increased blood pressure using different data sources. Relevant information, gathered from different data sources, was finally systematically organized into an Austin Bradford-Hill causality assessment framework to assess the causal relationship between omeprazole and hypertension.

Results: VigiBase indicated a total of 1043 cases of hypertension related to omeprazole from 36 different countries. In the global database, a statistical signal was triggered (IC025: 0.12) on association of omeprazole and hypertension. From the 1043 cases, 65.0% and 10.6% were reported as 'serious' and 'fatal', respectively. Hypertension resolved following withdrawal of omeprazole in 85 cases and recurred after re-introduction of the suspect drug in 14 cases. In 225 cases, omeprazole was the only suspected drug, while in 122 cases, omeprazole was the sole drug administered. When only these 122 cases were considered, 29 cases had positive dechallenge, four cases were with positive rechallenge and the median time-to-onset was 2 days. Literature search identified a possible biological mechanism and some experimental evidence that indicates omeprazole could possibly cause hypertension.

Conclusion: Currently available totality of evidence suggests there is a possible causal relationship between omeprazole and hypertension. Hence, it is recommended to monitor and report any incidence of hypertension related to omeprazole, and further epidemiological studies are recommended to corroborate the suggested causal association.

简介关于奥美拉唑与高血压之间的关系,文献记载很少。主要监管机构批准的奥美拉唑产品特征概要中并未提及高血压是一种药物不良反应。本研究由当地报告的一个病例引发,旨在评估奥美拉唑与高血压之间可能存在的因果关系:方法:检索了 2024 年 3 月 5 日世界卫生组织全球数据库 VigiBase 中全球报告的使用奥美拉唑后出现高血压的病例,并进行了描述性分析。此外,还利用不同的数据来源进行文献检索,以确定奥美拉唑与高血压或血压升高之间关联的临床前、临床和流行病学信息。最后,将从不同数据来源收集到的相关信息系统地整理到奥斯汀-布拉德福德-希尔因果关系评估框架中,以评估奥美拉唑与高血压之间的因果关系:VigiBase显示,共有来自36个不同国家的1043例高血压患者与奥美拉唑有关。在全球数据库中,奥美拉唑与高血压的相关性触发了统计信号(IC025:0.12)。在 1043 个病例中,分别有 65.0% 和 10.6% 的病例被报告为 "严重 "和 "致命"。85 例高血压患者在停用奥美拉唑后症状缓解,14 例在重新使用可疑药物后复发。在 225 例病例中,奥美拉唑是唯一的可疑药物,而在 122 例病例中,奥美拉唑是唯一的用药。仅考虑这 122 个病例,29 个病例的去挑战试验呈阳性,4 个病例的再挑战试验呈阳性,中位发病时间为 2 天。文献检索发现了奥美拉唑可能导致高血压的生物学机制和一些实验证据:结论:现有的全部证据表明,奥美拉唑与高血压之间可能存在因果关系。因此,建议监测和报告任何与奥美拉唑有关的高血压发病率,并建议进一步开展流行病学研究,以证实所建议的因果关系。
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引用次数: 0
Assessing the Costs of Intravenous Push Waste in Intraoperative Areas Through Observation: A Multi-site Study. 通过观察评估术中静脉推注废物的成本:多地点研究。
IF 1.9 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-10-10 DOI: 10.1007/s40801-024-00456-9
John B Hertig, Les Louden, Blake Shay, Armando Soto, Garrett Robbins, Tatyana Kornilova, Prachi Arora

Introduction: The costs associated with proper disposal, management, and regulatory compliance of controlled substances in healthcare systems are substantial. In the context of the current opioid crisis, and given the high abuse potential of controlled substances, it is imperative that waste is minimized and waste procedures are followed to ensure safe disposal of controlled substances. This study aims to quantify the costs associated with fentanyl, hydromorphone, morphine, midazolam, and ketamine waste in intraoperative areas through a multi-site observational analysis.

Methods: The study used an observational design across various hospital procedural and post-procedural units in the Southwest Florida region of the United States. Automated and non-automated workflows for wasting controlled substances were compared. As with a previous study conducted by Hertig et al., waste was evaluated as (1) the quantity (mg/μg) of medication disposed defined as 'pharmaceutical waste' or 'product waste' (PW); and (2) workforce time associated with the waste disposal process defined as 'workforce time waste' (WTW). Secondary measures include workforce costs associated with the waste disposal process. The product waste analysis was conducted between October and December 2023. The workforce time waste analysis was examined over a 10-day period in January and February 2024. A yearly extrapolation model was applied to cost data.

Results: The findings revealed substantial costs linked to both PW and WTW, emphasizing the financial burden of controlled substance waste. Study data validated previous literature describing the extent of fentanyl, hydromorphone, and morphine waste while documenting significant amounts of midazolam and ketamine waste. The combined annual waste cost for the two study hospitals was estimated at US$56,557, with workforce time accounting for 36%-50% of this total cost.

Conclusion: This study provides vital insights into the financial and operational impact of medication waste in procedural and post-procedural areas, supporting ongoing efforts to minimize waste, ensuring the safe and effective use of controlled substances. Future research should explore the impact of medication waste across diverse healthcare settings and the cost implications associated with pharmacy professionals in the waste compliance process.

导言:在医疗保健系统中,与妥善处置、管理和遵守受控物质法规相关的成本非常高昂。在当前阿片类药物危机的背景下,考虑到受控物质的高滥用可能性,当务之急是最大限度地减少废物,并遵循废物处理程序,以确保受控物质的安全处置。本研究旨在通过多地点观察分析,量化术中区域芬太尼、氢吗啡酮、吗啡、咪达唑仑和氯胺酮废物的相关成本:该研究采用了观察设计,涉及美国西南佛罗里达地区多家医院的手术室和术后病房。对浪费受控物质的自动化和非自动化工作流程进行了比较。与 Hertig 等人之前进行的一项研究一样,浪费的评估指标包括:(1) 定义为 "药物浪费 "或 "产品浪费"(PW)的药物处置量(毫克/微克);(2) 定义为 "劳动力时间浪费"(WTW)的与浪费处置过程相关的劳动力时间。次要衡量指标包括与废物处理过程相关的劳动力成本。产品浪费分析在 2023 年 10 月至 12 月期间进行。劳动力时间浪费分析在 2024 年 1 月和 2 月的 10 天内进行。对成本数据采用了年度外推法模型:结果:研究结果表明,与公共工程和劳动力时间浪费相关的成本都很高,强调了受控物质浪费造成的经济负担。研究数据验证了之前描述芬太尼、氢吗啡酮和吗啡浪费程度的文献,同时还记录了大量的咪达唑仑和氯胺酮浪费。两家研究医院每年浪费的总成本估计为 56,557 美元,其中劳动力时间占总成本的 36%-50%:这项研究为了解程序中和程序后的药物浪费对财务和运营的影响提供了重要依据,有助于不断努力减少浪费,确保安全有效地使用受控物质。未来的研究应探索药物浪费在不同医疗机构中的影响,以及与药学专业人员在浪费合规过程中相关的成本影响。
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引用次数: 0
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