Hirokazu Takatsuka, Takato Sugawara, M. Uchida, S. Yamazaki, Takaaki Suzuki, Naoya Kanogawa, S. Ogasawara, Y. Shiko, Yohei Kawasaki, Naoya Kato, I. Ishii
Introduction. The aim of this study was to evaluate the practicality of the signal transducer and activator of transcription (STAT) 3 polymorphisms as a predictive biomarker and sorafenib trough concentration as a monitoring biomarker for hand-foot skin reaction (HFSR) in patients with hepatocellular carcinoma (HCC). Methods. In total, 43 Japanese HCC patients were included. Sorafenib concentrations were measured, if possible, on days 8, 29, 35, and 57. The sorafenib concentration on day 8 (Cday8) was used for the analysis of HFSR occurring up to day 29. The median concentration for each patient (Cmedian) was used for HFSR occurring up to day 57 (study period). The STAT3 single nucleotide polymorphism (SNP) rs4796793 was determined using cell-free DNA extracted from plasma. Result. The Cday8 tended to be higher in the HFSR onset or grade ≥ 2 HFSR severity group than in the non-HFSR or grade ≤ 1 HFSR severity group. The Cmedian was significantly higher in the HFSR onset or grade ≥ 2 group than in the non-HFSR or grade ≤ 1 HFSR group. The Cmedian thresholds for predicting HFSR onset and severity were 3.62 μg/mL and 6.10 μg/mL, respectively. There was no association between STAT3 rs4796793 and HFSR onset or severity. In multivariate analysis, Cmedian values ≥ 3.62 μg/mL and >6.10 μg/mL were associated with the increased risk of HFSR onset (odds ratio: 16.6, p < 0.01) and severity (odds ratio: 15.7, p < 0.01), respectively. Conclusion. Monitoring of the sorafenib trough concentration may be practical for avoiding HFSR.
{"title":"Practicality of STAT3 Gene Polymorphisms and Sorafenib Trough Concentration as Biomarkers for Sorafenib-Induced Hand-Foot Skin Reaction in Hepatocellular Carcinoma","authors":"Hirokazu Takatsuka, Takato Sugawara, M. Uchida, S. Yamazaki, Takaaki Suzuki, Naoya Kanogawa, S. Ogasawara, Y. Shiko, Yohei Kawasaki, Naoya Kato, I. Ishii","doi":"10.1155/2023/6682459","DOIUrl":"https://doi.org/10.1155/2023/6682459","url":null,"abstract":"Introduction. The aim of this study was to evaluate the practicality of the signal transducer and activator of transcription (STAT) 3 polymorphisms as a predictive biomarker and sorafenib trough concentration as a monitoring biomarker for hand-foot skin reaction (HFSR) in patients with hepatocellular carcinoma (HCC). Methods. In total, 43 Japanese HCC patients were included. Sorafenib concentrations were measured, if possible, on days 8, 29, 35, and 57. The sorafenib concentration on day 8 (Cday8) was used for the analysis of HFSR occurring up to day 29. The median concentration for each patient (Cmedian) was used for HFSR occurring up to day 57 (study period). The STAT3 single nucleotide polymorphism (SNP) rs4796793 was determined using cell-free DNA extracted from plasma. Result. The Cday8 tended to be higher in the HFSR onset or grade ≥ 2 HFSR severity group than in the non-HFSR or grade ≤ 1 HFSR severity group. The Cmedian was significantly higher in the HFSR onset or grade ≥ 2 group than in the non-HFSR or grade ≤ 1 HFSR group. The Cmedian thresholds for predicting HFSR onset and severity were 3.62 μg/mL and 6.10 μg/mL, respectively. There was no association between STAT3 rs4796793 and HFSR onset or severity. In multivariate analysis, Cmedian values ≥ 3.62 μg/mL and >6.10 μg/mL were associated with the increased risk of HFSR onset (odds ratio: 16.6, \u0000 \u0000 p\u0000 \u0000 < 0.01) and severity (odds ratio: 15.7, \u0000 \u0000 p\u0000 \u0000 < 0.01), respectively. Conclusion. Monitoring of the sorafenib trough concentration may be practical for avoiding HFSR.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44141107","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}
Purpose. Atherosclerosis of arteries in the legs leads to peripheral arterial disease (PAD), increasing the risk of future cardiovascular events. Worldwide prevalence estimates indicate >200 million people have PAD, but this is likely underestimated given the variability in symptoms and lack of awareness by patients and clinicians. Antiplatelet therapy is recommended to reduce cardiovascular risk, but anticoagulation therapy may also be beneficial. This narrative review examined scientific literature for the burden and medical management of PAD, including use of anticoagulants in this population, and provides perspectives on the role of pharmacists to improve outcomes of PAD. Summary. A variety of antiplatelet therapies has been studied in patients with PAD, and treatment is recommended for those with symptomatic disease. The use of dual antiplatelet therapy is limited to patients with symptomatic PAD after revascularization. Anticoagulation with warfarin in combination with antiplatelet therapy did not improve efficacy over antiplatelet therapy alone and increased bleeding. In contrast, the direct factor Xa inhibitor rivaroxaban, when used in combination with low-dose aspirin, has been shown to significantly reduce the risk of cardiovascular death, myocardial infarction (MI), or stroke by 28% in patients with PAD compared with aspirin alone. Similarly, in patients with PAD who have undergone revascularization, rivaroxaban plus aspirin reduced the risk of acute limb ischemia, major amputation, MI, stroke, or cardiovascular death by 15% versus aspirin alone. Major bleeding was significantly increased with rivaroxaban plus aspirin, but with no differences in fatal bleeding, nonfatal intracranial hemorrhage, or symptomatic bleeding into a critical organ between groups. Pharmacist-led interventions for patients with PAD include identifying at-risk patients through medication reviews and clinical assessments, education and monitoring use of prescription and over-the-counter medications, and appropriate counseling on lifestyle modifications. Conclusion. Rivaroxaban plus aspirin reduces the risk of major cardiovascular events, including major adverse limb events and amputation, in patients with PAD. Pharmacists can play an integral role in identifying, screening, and managing patients with PAD to achieve favorable outcomes.
{"title":"Peripheral Arterial Disease and the Pharmacist’s Role in Management","authors":"Zachary A. Stacy","doi":"10.1155/2023/2352051","DOIUrl":"https://doi.org/10.1155/2023/2352051","url":null,"abstract":"Purpose. Atherosclerosis of arteries in the legs leads to peripheral arterial disease (PAD), increasing the risk of future cardiovascular events. Worldwide prevalence estimates indicate >200 million people have PAD, but this is likely underestimated given the variability in symptoms and lack of awareness by patients and clinicians. Antiplatelet therapy is recommended to reduce cardiovascular risk, but anticoagulation therapy may also be beneficial. This narrative review examined scientific literature for the burden and medical management of PAD, including use of anticoagulants in this population, and provides perspectives on the role of pharmacists to improve outcomes of PAD. Summary. A variety of antiplatelet therapies has been studied in patients with PAD, and treatment is recommended for those with symptomatic disease. The use of dual antiplatelet therapy is limited to patients with symptomatic PAD after revascularization. Anticoagulation with warfarin in combination with antiplatelet therapy did not improve efficacy over antiplatelet therapy alone and increased bleeding. In contrast, the direct factor Xa inhibitor rivaroxaban, when used in combination with low-dose aspirin, has been shown to significantly reduce the risk of cardiovascular death, myocardial infarction (MI), or stroke by 28% in patients with PAD compared with aspirin alone. Similarly, in patients with PAD who have undergone revascularization, rivaroxaban plus aspirin reduced the risk of acute limb ischemia, major amputation, MI, stroke, or cardiovascular death by 15% versus aspirin alone. Major bleeding was significantly increased with rivaroxaban plus aspirin, but with no differences in fatal bleeding, nonfatal intracranial hemorrhage, or symptomatic bleeding into a critical organ between groups. Pharmacist-led interventions for patients with PAD include identifying at-risk patients through medication reviews and clinical assessments, education and monitoring use of prescription and over-the-counter medications, and appropriate counseling on lifestyle modifications. Conclusion. Rivaroxaban plus aspirin reduces the risk of major cardiovascular events, including major adverse limb events and amputation, in patients with PAD. Pharmacists can play an integral role in identifying, screening, and managing patients with PAD to achieve favorable outcomes.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49328700","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}
Lin Liu, Quan Shen, Yan Wang, Hong Li, Jingshan Zhao
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease. Previous studies have shown that dihydromyricetin (DHM) is beneficial for NAFLD. However, whether DHM alleviates NAFLD by inhibiting liver endoplasmic reticulum (ER) stress remains unknown. Thus, this study aimed to identify the potential roles and mechanisms of DHM. Twenty-four male low-density lipoprotein receptor (LDLR−/−) knockout mice aged 8 weeks were randomly divided into normal control, control, and DHM groups. Normal control mice were fed a normal diet (ND), and the last two groups of mice were fed a high-fat and high-fructose diet (HFD) for 12 weeks, treated with or without DHM. DHM alleviated diet-induced hyperlipidemia as early as 4 weeks after and until the end of HFD feeding. HFD increased insulin resistance, and the opposite was observed in the DHM group. Compared to the control group, the body weight of the mice and adipocyte size and weight of the retroperitoneal and epididymal fat were remarkably reduced in the DHM group. The expression of genes related to lipid metabolism, such as Acox1 and Cpt1α, was significantly upregulated. Moreover, Mttp was downregulated in the two fat sits in the DHM group. DHM alleviated diet-induced lipid deposition in the liver and decreased liver triglyceride and total cholesterol content. DHM improved liver function by inhibiting ER stress, alleviating atherogenesis, and promoting vascular remodeling. In conclusion, dihydromyricetin improved NAFLD and related insulin resistance, hyperlipidemia, and atherogenesis by inhibiting liver ER stress in HFD-fed LDLR−/− mice.
{"title":"Dihydromyricetin Alleviates Nonalcoholic Fatty Liver Disease and Its Associated Metabolic Syndrome by Inhibiting Endoplasmic Reticulum Stress in LDLR−/− Mice Fed with a High-Fat and High-Fructose Diet","authors":"Lin Liu, Quan Shen, Yan Wang, Hong Li, Jingshan Zhao","doi":"10.1155/2023/5029934","DOIUrl":"https://doi.org/10.1155/2023/5029934","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease. Previous studies have shown that dihydromyricetin (DHM) is beneficial for NAFLD. However, whether DHM alleviates NAFLD by inhibiting liver endoplasmic reticulum (ER) stress remains unknown. Thus, this study aimed to identify the potential roles and mechanisms of DHM. Twenty-four male low-density lipoprotein receptor (LDLR−/−) knockout mice aged 8 weeks were randomly divided into normal control, control, and DHM groups. Normal control mice were fed a normal diet (ND), and the last two groups of mice were fed a high-fat and high-fructose diet (HFD) for 12 weeks, treated with or without DHM. DHM alleviated diet-induced hyperlipidemia as early as 4 weeks after and until the end of HFD feeding. HFD increased insulin resistance, and the opposite was observed in the DHM group. Compared to the control group, the body weight of the mice and adipocyte size and weight of the retroperitoneal and epididymal fat were remarkably reduced in the DHM group. The expression of genes related to lipid metabolism, such as Acox1 and Cpt1α, was significantly upregulated. Moreover, Mttp was downregulated in the two fat sits in the DHM group. DHM alleviated diet-induced lipid deposition in the liver and decreased liver triglyceride and total cholesterol content. DHM improved liver function by inhibiting ER stress, alleviating atherogenesis, and promoting vascular remodeling. In conclusion, dihydromyricetin improved NAFLD and related insulin resistance, hyperlipidemia, and atherogenesis by inhibiting liver ER stress in HFD-fed LDLR−/− mice.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43053042","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}
Wenyu Jiang, Shasha Wu, Meijiao Lu, Jiahui Tian, X. Cui, Xiaqiong Mao, C. Jiao, N. Tang, Jingjing Ma, Hongjie Zhang
Background. NUDT15 gene polymorphisms have been identified to predispose Asian patients with an inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study predicted the influence of NUDT15 haplotypes and diplotypes on azathioprine (AZA)-induced leukopenia as well as the long-term influence of AZA on hematologic parameters in IBD. Methods. 194 IBD patients were tested for NUDT15 genotypes. We collected clinical data of 80 patients with AZA treatment including adverse events, dosage, white blood cell (WBC) count, platelet (PLT) count, and mean corpuscular volume (MCV) after AZA initiation. Patients without adverse events and drug withdrawal were followed up for at least one year. The relationship between NUDT15 haplotypes and diplotypes and leukopenia was analyzed. Results. The haplotypes NUDT15 c.415C > T and c.36_37insGGAGTC as well as the diplotypes NUDT15 ∗ 1/ ∗ 2, ∗ 3/ ∗ 3, and ∗ 3/ ∗ 5 were significantly associated with AZA-induced leukopenia. Only one patient with NUDT15 c.52G > A experienced leukopenia. NUDT15 ∗ 1/ ∗ 3 was not associated with leukopenia. After AZA initiation, the WBC count showed a downward trend in both wild types and mutants. The mean of WBC count in the mutant group at 1st month after AZA initiation was lower than that in the wild-type group ( P = 0.006 ). The MCV increased gradually in mutant cases ( P = 0.039 ), and the differences were obvious at 6th and 12th months compared with the baseline ( P = 0.014 a n d P = 0.042 , respectively). The PLT count showed a decreasing trend in the mutant group, but there was no difference until 11 months after initiating treatment ( P = 0.023 ). The final dose of AZA in the NUDT15 mutant group was significantly lower than that in the wild-type group ( P = 0.006 ). Conclusion. NUDT15 polymorphisms may be an appropriate predictor of AZA abnormal hematologic indices in IBD patients. It is necessary for IBD patients to monitor hematological indices and optimize AZA therapy.
{"title":"NUDT15 Haplotypes and Diplotypes Predict Thiopurine-Induced Leukopenia and the Influence of Prolonged Exposure to Azathioprine on Hematologic Indices in Patients with Inflammatory Bowel Diseases","authors":"Wenyu Jiang, Shasha Wu, Meijiao Lu, Jiahui Tian, X. Cui, Xiaqiong Mao, C. Jiao, N. Tang, Jingjing Ma, Hongjie Zhang","doi":"10.1155/2023/3000409","DOIUrl":"https://doi.org/10.1155/2023/3000409","url":null,"abstract":"Background. NUDT15 gene polymorphisms have been identified to predispose Asian patients with an inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study predicted the influence of NUDT15 haplotypes and diplotypes on azathioprine (AZA)-induced leukopenia as well as the long-term influence of AZA on hematologic parameters in IBD. Methods. 194 IBD patients were tested for NUDT15 genotypes. We collected clinical data of 80 patients with AZA treatment including adverse events, dosage, white blood cell (WBC) count, platelet (PLT) count, and mean corpuscular volume (MCV) after AZA initiation. Patients without adverse events and drug withdrawal were followed up for at least one year. The relationship between NUDT15 haplotypes and diplotypes and leukopenia was analyzed. Results. The haplotypes NUDT15 c.415C > T and c.36_37insGGAGTC as well as the diplotypes NUDT15 \u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 1/\u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 2, \u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 3/\u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 3, and \u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 3/\u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 5 were significantly associated with AZA-induced leukopenia. Only one patient with NUDT15 c.52G > A experienced leukopenia. NUDT15 \u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 1/\u0000 \u0000 \u0000 \u0000 ∗\u0000 \u0000 \u0000 3 was not associated with leukopenia. After AZA initiation, the WBC count showed a downward trend in both wild types and mutants. The mean of WBC count in the mutant group at 1st month after AZA initiation was lower than that in the wild-type group (\u0000 \u0000 P\u0000 =\u0000 0.006\u0000 \u0000 ). The MCV increased gradually in mutant cases (\u0000 \u0000 P\u0000 =\u0000 0.039\u0000 \u0000 ), and the differences were obvious at 6th and 12th months compared with the baseline (\u0000 \u0000 P\u0000 =\u0000 0.014\u0000 \u0000 a\u0000 n\u0000 d\u0000 \u0000 P\u0000 =\u0000 0.042\u0000 \u0000 , respectively). The PLT count showed a decreasing trend in the mutant group, but there was no difference until 11 months after initiating treatment (\u0000 \u0000 P\u0000 =\u0000 0.023\u0000 \u0000 ). The final dose of AZA in the NUDT15 mutant group was significantly lower than that in the wild-type group (\u0000 \u0000 P\u0000 =\u0000 0.006\u0000 \u0000 ). Conclusion. NUDT15 polymorphisms may be an appropriate predictor of AZA abnormal hematologic indices in IBD patients. It is necessary for IBD patients to monitor hematological indices and optimize AZA therapy.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45427859","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}
Ahmed Alastal, Amani D. Abu Kwaik, Azzam A. Malkawi, Sarah Baltzley, Abeer M. Al-Ghananeem
Objective. Dihydroergotamine (DHE) is used for acute migraine treatment. Oral DHE is extensively metabolized; therefore, it must be given by a nonoral route. The aim of this study was to investigate the potential use of chitosan nanoparticles as a system for improving the systemic absorption of dihydroergotamine (DHE) following nasal administration. Methods. DHE-loaded chitosan nanoparticles (CS-NPs) were prepared by a modified ionotropic gelation method with sodium tripolyphosphate. The resulting nanoparticles were evaluated for size, drug loading, and in vitro release. DHE was administered at a dose of 0.5 mg/kg to male Sprague–Dawley rats intravenously, as an intranasal solution, or intranasal nanoparticles (n = 3 in each group). A special surgical procedure was performed to ensure that the drug solution was held in the nasal cavity. Blood samples were collected at appropriate times for 90 min. An HPLC-fluorescence detection method was employed to determine DHE in the plasma. Results. DHE chitosan nanoparticles with 20% loading had 95 ± 13% encapsulation efficiency and a particle size of 395 ± 59 nm. In vitro DHE release studies showed an initial burst followed by a slow release of DHE. DHE intranasal nanoparticles demonstrated significantly increased absolute bioavailability (82.5 ± 12.3%) over intranasal DHE solution administration (53.2 ± 7.7%). Conclusion. Taking in consideration the limitations of delivering DHE, the results of the present study demonstrate that DHE CS-NPs have a great potential for nasal DHE administration (55% increase in bioavailability) compared to intranasal solution with effective systemic absorption.
{"title":"Enhancing Intranasal Delivery and Bioavailability of Dihydroergotamine Utilizing Chitosan Nanoparticles","authors":"Ahmed Alastal, Amani D. Abu Kwaik, Azzam A. Malkawi, Sarah Baltzley, Abeer M. Al-Ghananeem","doi":"10.1155/2023/2284371","DOIUrl":"https://doi.org/10.1155/2023/2284371","url":null,"abstract":"Objective. Dihydroergotamine (DHE) is used for acute migraine treatment. Oral DHE is extensively metabolized; therefore, it must be given by a nonoral route. The aim of this study was to investigate the potential use of chitosan nanoparticles as a system for improving the systemic absorption of dihydroergotamine (DHE) following nasal administration. Methods. DHE-loaded chitosan nanoparticles (CS-NPs) were prepared by a modified ionotropic gelation method with sodium tripolyphosphate. The resulting nanoparticles were evaluated for size, drug loading, and in vitro release. DHE was administered at a dose of 0.5 mg/kg to male Sprague–Dawley rats intravenously, as an intranasal solution, or intranasal nanoparticles (n = 3 in each group). A special surgical procedure was performed to ensure that the drug solution was held in the nasal cavity. Blood samples were collected at appropriate times for 90 min. An HPLC-fluorescence detection method was employed to determine DHE in the plasma. Results. DHE chitosan nanoparticles with 20% loading had 95 ± 13% encapsulation efficiency and a particle size of 395 ± 59 nm. In vitro DHE release studies showed an initial burst followed by a slow release of DHE. DHE intranasal nanoparticles demonstrated significantly increased absolute bioavailability (82.5 ± 12.3%) over intranasal DHE solution administration (53.2 ± 7.7%). Conclusion. Taking in consideration the limitations of delivering DHE, the results of the present study demonstrate that DHE CS-NPs have a great potential for nasal DHE administration (55% increase in bioavailability) compared to intranasal solution with effective systemic absorption.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43603071","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}
Background. Patients with multiple chronic conditions often have complex medication regimes which negatively impact their health-related quality of life (HRQoL), and there is limited evidence on this topic, particularly from the resource limiting set-up. Hence, this study is aimed at assessing the impact of medication regimen complexity on HRQoL in patients with multiple chronic conditions at a university hospital in Ethiopia. Method. A cross-sectional study was conducted on adult patients who had at least two long-term diseases and were already receiving medical therapy for the relevant disorders. The validated 65-item Medication Regimen Complexity Index (MRCI) and the EuroQol-5-Dimensions-5-Levels (EQ-5D-5L) instruments were used to assess MRC and HRQoL, respectively. The Welch test for unequal variance and Fisher’s exact test were used to assess the impact of different variables on HRQoL. Results. The study surveyed 416 participants, with a 98.3% response rate, the majority of whom were female (n = 267, 64.2%) and had two chronic conditions (n = 215, 51.7%). About 46.4% of patients were taking five or more medications, with a significantly higher proportion at the high regimen complexity level ( P = 0.001 ). The average MRCI score was 9.73 ± 3.38, indicating a high level of complexity. Patients with high MRCI scores reported more problems in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There was a negative correlation between the MRCI score and HRQoL as measured by the EQ-5D-Index (r = −0.175; P < 0.001 ) and the EuroQol-Visual Analogue Scale score (r = −0.151; P = 0.002 ). In addition, there was a statistically significant difference in the mean EQ-5D-Index ( P = 0.001 ) and EQ-VAS scores ( P = 0.001 ) across low, medium, and high MRCI levels. Conclusion. Medication regimen complexity was prevalent among patients with multimorbidity and was associated with a decrease in HRQoL. Therefore, interventions addressing medication-related issues should be a priority to improve the well-being of patients with multiple chronic conditions.
{"title":"Exploring the Impact of Medication Regimen Complexity on Health-Related Quality of Life in Patients with Multimorbidity","authors":"B. M. Gebresillassie, Abebe Tarekegn Kassaw","doi":"10.1155/2023/1744472","DOIUrl":"https://doi.org/10.1155/2023/1744472","url":null,"abstract":"Background. Patients with multiple chronic conditions often have complex medication regimes which negatively impact their health-related quality of life (HRQoL), and there is limited evidence on this topic, particularly from the resource limiting set-up. Hence, this study is aimed at assessing the impact of medication regimen complexity on HRQoL in patients with multiple chronic conditions at a university hospital in Ethiopia. Method. A cross-sectional study was conducted on adult patients who had at least two long-term diseases and were already receiving medical therapy for the relevant disorders. The validated 65-item Medication Regimen Complexity Index (MRCI) and the EuroQol-5-Dimensions-5-Levels (EQ-5D-5L) instruments were used to assess MRC and HRQoL, respectively. The Welch test for unequal variance and Fisher’s exact test were used to assess the impact of different variables on HRQoL. Results. The study surveyed 416 participants, with a 98.3% response rate, the majority of whom were female (n = 267, 64.2%) and had two chronic conditions (n = 215, 51.7%). About 46.4% of patients were taking five or more medications, with a significantly higher proportion at the high regimen complexity level (\u0000 \u0000 P\u0000 =\u0000 0.001\u0000 \u0000 ). The average MRCI score was 9.73 ± 3.38, indicating a high level of complexity. Patients with high MRCI scores reported more problems in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There was a negative correlation between the MRCI score and HRQoL as measured by the EQ-5D-Index (r = −0.175; \u0000 \u0000 P\u0000 <\u0000 0.001\u0000 \u0000 ) and the EuroQol-Visual Analogue Scale score (r = −0.151; \u0000 \u0000 P\u0000 =\u0000 0.002\u0000 \u0000 ). In addition, there was a statistically significant difference in the mean EQ-5D-Index (\u0000 \u0000 P\u0000 =\u0000 0.001\u0000 \u0000 ) and EQ-VAS scores (\u0000 \u0000 P\u0000 =\u0000 0.001\u0000 \u0000 ) across low, medium, and high MRCI levels. Conclusion. Medication regimen complexity was prevalent among patients with multimorbidity and was associated with a decrease in HRQoL. Therefore, interventions addressing medication-related issues should be a priority to improve the well-being of patients with multiple chronic conditions.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48091487","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}
A. Dahal, K. Shrestha, R. Karki, Saraswati Bhattarai, Shiva Aryal, S. Deo, B. Regmi, M. Willcox, S. K. Mishra
Background. Various antibiotics are prescribed empirically by physicians to cope with infections in renal disease patients. A urinary tract infection (UTI) is often caused by biofilm-forming multidrug-resistant (MDR) uropathogens. This study aimed to analyze the antibiogram of UTI strains from renal disease patients and the biofilm-forming ability of those strains. Methods. 102 patients clinically diagnosed with a UTI and renal disease were recruited into the study from August 2017 to January 2018. Clean-catch midstream urine samples were processed for the isolation and identification of the bacteria following standard methodologies. The antibiogram of the isolates (n = 106) was produced by the Kirby–Bauer disc diffusion method. Detection of biofilm formation was performed in tissue culture plates. Results. The incidence of a UTI in renal disease was 19.1%. Most patients were diagnosed with chronic kidney disease (18.63%), nephrotic syndrome (16.67%), and nephrolithiasis (14.71%). The commonest uropathogens were Escherichia coli (52.8%), Klebsiella pneumoniae (16%), and Enterococcus spp. (15.0%). Ceftriaxone was the most common antibiotic prescribed empirically (37%), whereas nitrofurantoin was the most prescribed antibiotic as adjusted therapy (36.1%). Among the first- and second-line antibiotics, most Gram-negative bacteria were sensitive to amikacin (70.7%), meropenem (70.7%), cefoperazone-sulbactam (70.0%), piperacillin-tazobactam (67.2%), gentamicin (66.7%), and nitrofurantoin (66.7%). Most Gram-positive bacteria were sensitive to doxycycline (90.0%), nitrofurantoin (72.2%), gentamicin (66.7%), and tetracycline (62.5%). All MDR Gram-negative uropathogens were susceptible to colistin sulfate and polymyxin B. Among the 106 isolates, 74.5% produced biofilms and 70.8% were MDR. In 67.0% of cases, including both MDR and biofilm-producing bacteria, the empirical therapy needed adjustment. Conclusions. Aminoglycoside, carbapenem, beta-lactam inhibitor, and nitrofuran group of antibiotics may be the optimal first-line empirical therapies for uropathogens in hospitalized renal disease patients. Regular surveillance of resistance patterns and the study of biofilm formation in uropathogens must be performed to ensure effective management of the patients.
{"title":"Antimicrobial Resistance and Biofilm Production in Uropathogens from Renal Disease Patients Admitted to Tribhuvan University Teaching Hospital, Nepal","authors":"A. Dahal, K. Shrestha, R. Karki, Saraswati Bhattarai, Shiva Aryal, S. Deo, B. Regmi, M. Willcox, S. K. Mishra","doi":"10.1155/2023/4867817","DOIUrl":"https://doi.org/10.1155/2023/4867817","url":null,"abstract":"Background. Various antibiotics are prescribed empirically by physicians to cope with infections in renal disease patients. A urinary tract infection (UTI) is often caused by biofilm-forming multidrug-resistant (MDR) uropathogens. This study aimed to analyze the antibiogram of UTI strains from renal disease patients and the biofilm-forming ability of those strains. Methods. 102 patients clinically diagnosed with a UTI and renal disease were recruited into the study from August 2017 to January 2018. Clean-catch midstream urine samples were processed for the isolation and identification of the bacteria following standard methodologies. The antibiogram of the isolates (n = 106) was produced by the Kirby–Bauer disc diffusion method. Detection of biofilm formation was performed in tissue culture plates. Results. The incidence of a UTI in renal disease was 19.1%. Most patients were diagnosed with chronic kidney disease (18.63%), nephrotic syndrome (16.67%), and nephrolithiasis (14.71%). The commonest uropathogens were Escherichia coli (52.8%), Klebsiella pneumoniae (16%), and Enterococcus spp. (15.0%). Ceftriaxone was the most common antibiotic prescribed empirically (37%), whereas nitrofurantoin was the most prescribed antibiotic as adjusted therapy (36.1%). Among the first- and second-line antibiotics, most Gram-negative bacteria were sensitive to amikacin (70.7%), meropenem (70.7%), cefoperazone-sulbactam (70.0%), piperacillin-tazobactam (67.2%), gentamicin (66.7%), and nitrofurantoin (66.7%). Most Gram-positive bacteria were sensitive to doxycycline (90.0%), nitrofurantoin (72.2%), gentamicin (66.7%), and tetracycline (62.5%). All MDR Gram-negative uropathogens were susceptible to colistin sulfate and polymyxin B. Among the 106 isolates, 74.5% produced biofilms and 70.8% were MDR. In 67.0% of cases, including both MDR and biofilm-producing bacteria, the empirical therapy needed adjustment. Conclusions. Aminoglycoside, carbapenem, beta-lactam inhibitor, and nitrofuran group of antibiotics may be the optimal first-line empirical therapies for uropathogens in hospitalized renal disease patients. Regular surveillance of resistance patterns and the study of biofilm formation in uropathogens must be performed to ensure effective management of the patients.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46864844","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}
Victoria Rollinson, Neil French, R. Turner, M. Pirmohamed
Objective. The aim of this exploratory study was to ascertain the current educational status of pharmacogenomics (PGx) within the present and future UK pharmacy profession, in addition to ascertaining future educational and infrastructure needs of pharmacists to adopt PGx into practice. Methods. A 35-question survey was sent electronically to practicing pharmacists, preregistration pharmacists, and Master of Pharmacy (MPharm) students throughout the UK between April 2018 and May 2019. Responses were anonymous and analysed using GraphPad Prism 8 and SPSS statistics 26. Results. In total, 264 participants, where data could be used for analysis, responded to the survey. This comprised 196 practicing pharmacists and 68 preregistration pharmacists/MPharm students. The findings demonstrated variation in undergraduate level exposure to PGx between those who had qualified within the past 10 years and those who had qualified over 10 years ago. Over 60% of qualified pharmacists did not feel confident in identifying drugs that require PGx testing. Nearly three quarters of respondents cited that PGx guidelines were needed to help facilitate a PGx service, although 63.6% also stated that they had previously never looked for a PGx recommendation. Most respondents cited PGx as a low or medium learning priority. Conclusion. Our survey suggests that further education is required to prepare the UK pharmacy workforce for the advent of PGx. A focus on the provision of, and education around, PGx guidelines is needed. In addition, the disparity identified between pharmacists at different stages of their career will need to be addressed with tailored and targeted educational packages.
{"title":"A Survey of the UK Pharmacy Profession’s Educational Needs on Pharmacogenomics","authors":"Victoria Rollinson, Neil French, R. Turner, M. Pirmohamed","doi":"10.1155/2023/2388845","DOIUrl":"https://doi.org/10.1155/2023/2388845","url":null,"abstract":"Objective. The aim of this exploratory study was to ascertain the current educational status of pharmacogenomics (PGx) within the present and future UK pharmacy profession, in addition to ascertaining future educational and infrastructure needs of pharmacists to adopt PGx into practice. Methods. A 35-question survey was sent electronically to practicing pharmacists, preregistration pharmacists, and Master of Pharmacy (MPharm) students throughout the UK between April 2018 and May 2019. Responses were anonymous and analysed using GraphPad Prism 8 and SPSS statistics 26. Results. In total, 264 participants, where data could be used for analysis, responded to the survey. This comprised 196 practicing pharmacists and 68 preregistration pharmacists/MPharm students. The findings demonstrated variation in undergraduate level exposure to PGx between those who had qualified within the past 10 years and those who had qualified over 10 years ago. Over 60% of qualified pharmacists did not feel confident in identifying drugs that require PGx testing. Nearly three quarters of respondents cited that PGx guidelines were needed to help facilitate a PGx service, although 63.6% also stated that they had previously never looked for a PGx recommendation. Most respondents cited PGx as a low or medium learning priority. Conclusion. Our survey suggests that further education is required to prepare the UK pharmacy workforce for the advent of PGx. A focus on the provision of, and education around, PGx guidelines is needed. In addition, the disparity identified between pharmacists at different stages of their career will need to be addressed with tailored and targeted educational packages.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42145484","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}
Objective. Metformin is a common antidiabetic drug that has been reported to serve as an anticancer agent in combination with other therapies. But the effect of the addition of metformin on the survival of non-small cell lung cancer (NSCLC) patients undergoing chemotherapy is still controversial. We conducted this systematic review to evaluate the survival effect of metformin added to chemotherapy in NSCLC patients. Methods. Electronic literature search was performed in the PubMed, Embase, and Web of Science databases from their inception up to April 2023. The study region, study design, histological subtype of the NSCLC, tumor stage, treatment strategy, sample size, follow-up duration, diabetes status, and HR of OS or PFS of the included studies were extracted. The quality was assessed through Cochrane collaboration’s tool for RCT and the Newcastle–Ottawa scale (NOS) for observational studies, respectively. Results and conclusions. Eleven studies with a total of 4606 patients were finally included. Five RCTs showed a high risk of bias due to the open-label nature while six retrospective studies were of high quality. Two studies of NSCLC patients with diabetes reported significant benefits in overall survival from metformin addition, while one study of patients without diabetes reported a negative effect on the survival of metformin addition. The survival impact of metformin added to chemotherapy on unresectable NSCLC patients remains inconclusive. The survival benefit might be more prominent in patients with diabetes, awaiting further evidence.
客观的二甲双胍是一种常见的抗糖尿病药物，据报道可作为抗癌剂与其他疗法联合使用。但二甲双胍对正在接受化疗的非小细胞肺癌（NSCLC）患者生存率的影响仍然存在争议。我们进行了这项系统综述，以评估二甲双胍在NSCLC患者化疗中的生存效果。方法。从成立到2023年4月，在PubMed、Embase和Web of Science数据库中进行了电子文献搜索。提取纳入研究的研究区域、研究设计、NSCLC的组织学亚型、肿瘤分期、治疗策略、样本量、随访时间、糖尿病状况以及OS或PFS的HR。质量分别通过Cochrane协作的RCT工具和纽卡斯尔-渥太华观察性研究量表（NOS）进行评估。结果和结论。最终纳入了11项研究，共4606名患者。五项随机对照试验显示，由于开放标签的性质，存在较高的偏倚风险，而六项回顾性研究的质量较高。两项针对患有糖尿病的NSCLC患者的研究报告称，添加二甲双胍对总生存率有显著益处，而一项针对未患有糖尿病的患者的研究则报告了添加二甲双胍对生存率的负面影响。二甲双胍联合化疗对不可切除的NSCLC患者的生存影响尚不确定。糖尿病患者的生存益处可能更为显著，有待进一步的证据。
{"title":"The Survival Effect of Metformin on Non-Small Cell Lung Cancer Treated with Chemotherapy: A Systematic Review","authors":"Qin Li, Qiao Fan, Ji Wu","doi":"10.1155/2023/5575513","DOIUrl":"https://doi.org/10.1155/2023/5575513","url":null,"abstract":"Objective. Metformin is a common antidiabetic drug that has been reported to serve as an anticancer agent in combination with other therapies. But the effect of the addition of metformin on the survival of non-small cell lung cancer (NSCLC) patients undergoing chemotherapy is still controversial. We conducted this systematic review to evaluate the survival effect of metformin added to chemotherapy in NSCLC patients. Methods. Electronic literature search was performed in the PubMed, Embase, and Web of Science databases from their inception up to April 2023. The study region, study design, histological subtype of the NSCLC, tumor stage, treatment strategy, sample size, follow-up duration, diabetes status, and HR of OS or PFS of the included studies were extracted. The quality was assessed through Cochrane collaboration’s tool for RCT and the Newcastle–Ottawa scale (NOS) for observational studies, respectively. Results and conclusions. Eleven studies with a total of 4606 patients were finally included. Five RCTs showed a high risk of bias due to the open-label nature while six retrospective studies were of high quality. Two studies of NSCLC patients with diabetes reported significant benefits in overall survival from metformin addition, while one study of patients without diabetes reported a negative effect on the survival of metformin addition. The survival impact of metformin added to chemotherapy on unresectable NSCLC patients remains inconclusive. The survival benefit might be more prominent in patients with diabetes, awaiting further evidence.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41719417","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}
What Is Known and Objective. Pyrotinib maleate, also known as pyrotinib, is an irreversible dual receptor tyrosine kinase inhibitor that primarily targets the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Cytochrome P450 3A4 (CYP3A4) enzyme mainly catalyzes pyrotinib, and its metabolism is influenced apparently by CYP3A4 strong inhibitor, but the effect of CYP3A4 moderate inhibitor is still unclear as a moderate inhibitor of CYP3A4 enzyme. This study evaluated the effect of fluconazole, a widespread antifungal medication, on the pharmacokinetics and safety tolerance of pyrotinib. Methods. This study was an open, single-dose, and self-controlled clinical trial. Eighteen healthy Chinese participants were enrolled in this study. All participants were administered fluconazole on days 6–18 and pyrotinib on days 1 and 9. The maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the concentration–time curve from time 0 to the last measurable concentration (AUC0−t), area under the concentration–time curve from time 0 extrapolated to infinity (AUC0−∞), terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent clearance (CL/F) were calculated using WinNonlin software (version 8.1). Safety tolerance was assessed throughout the process. Results and Discussion. Compared with the single administration of pyrotinib, the exposure level was enhanced significantly after the coadministration of pyrotinib and fluconazole. The geometric mean ratios (pyrotinib + fluconazole/pyrotinib alone) of Cmax, AUC0−t, and AUC0−∞ were 2.16, 3.6, and 3.5, respectively. The parameter of t1/2 is 14.16 h and 24.03 h, and CL/F is 275.06 L/h and 78.42 L/h, for pyrotinib alone and with fluconazole. No serious adverse events were reported in this trial, and no participant withdrew from the trial because of adverse events. What Is New and Conclusion. The PK profile of pyrotinib, a CYP3A4 substrate, was significantly influenced by fluconazole, with increased exposure levels and prolonged t1/2. Dosage adjustment is suggested for the clinical application of pyrotinib when coadministered with fluconazole or other CYP3A4 inhibitors/inducers.
{"title":"Effect of Fluconazole on the Pharmacokinetics of Pyrotinib Maleate: A Single-Center, Open, Single-Dose, Self-Controlled Study in Healthy Chinese Participants","authors":"Yuxuan Song, Wenyu Zhang, Peng-Jen Chen, Rui Liang, Hengli Zhao, Qing Wen","doi":"10.1155/2023/9514938","DOIUrl":"https://doi.org/10.1155/2023/9514938","url":null,"abstract":"What Is Known and Objective. Pyrotinib maleate, also known as pyrotinib, is an irreversible dual receptor tyrosine kinase inhibitor that primarily targets the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Cytochrome P450 3A4 (CYP3A4) enzyme mainly catalyzes pyrotinib, and its metabolism is influenced apparently by CYP3A4 strong inhibitor, but the effect of CYP3A4 moderate inhibitor is still unclear as a moderate inhibitor of CYP3A4 enzyme. This study evaluated the effect of fluconazole, a widespread antifungal medication, on the pharmacokinetics and safety tolerance of pyrotinib. Methods. This study was an open, single-dose, and self-controlled clinical trial. Eighteen healthy Chinese participants were enrolled in this study. All participants were administered fluconazole on days 6–18 and pyrotinib on days 1 and 9. The maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the concentration–time curve from time 0 to the last measurable concentration (AUC0−t), area under the concentration–time curve from time 0 extrapolated to infinity (AUC0−∞), terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent clearance (CL/F) were calculated using WinNonlin software (version 8.1). Safety tolerance was assessed throughout the process. Results and Discussion. Compared with the single administration of pyrotinib, the exposure level was enhanced significantly after the coadministration of pyrotinib and fluconazole. The geometric mean ratios (pyrotinib + fluconazole/pyrotinib alone) of Cmax, AUC0−t, and AUC0−∞ were 2.16, 3.6, and 3.5, respectively. The parameter of t1/2 is 14.16 h and 24.03 h, and CL/F is 275.06 L/h and 78.42 L/h, for pyrotinib alone and with fluconazole. No serious adverse events were reported in this trial, and no participant withdrew from the trial because of adverse events. What Is New and Conclusion. The PK profile of pyrotinib, a CYP3A4 substrate, was significantly influenced by fluconazole, with increased exposure levels and prolonged t1/2. Dosage adjustment is suggested for the clinical application of pyrotinib when coadministered with fluconazole or other CYP3A4 inhibitors/inducers.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48010467","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}
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