Abstract: Chronic hepatitis C (HCV) affects up to 3.25 million children and adolescents. Early treatment of HCV in children and adolescents reduces progression to advanced liver disease and cancer. Treatment for HCV has evolved to highly effective direct acting antiviral therapy in adults and now in children ≥ 3 years of age. This review focuses on the role of sofosbuvir and velpatasvir (SOF/VEL), a newer treatment of children and adolescents with chronic HCV. SOF/VEL is a pangenotypic DAA with primary clearance via the liver and biliary excretion. It has been studied in children and adolescents and is approved in the US for use in children and adolescents ≥ 3 years of age. Although the data are currently limited, SOF/VEL has demonstrated sustained viral response rates similar to comparable DAAs in the range of 95– 98%. To date, side effects have been minimal.
Keywords: pediatric hepatitis C, pediatric hepatitis C treatment
{"title":"Profile of Sofosbuvir and Velpatasvir Combination in the Treatment of Chronic Hepatitis C in Children and Adolescents: Current Evidence","authors":"Dania Brigham, Michael R Narkewicz","doi":"10.2147/tcrm.s326099","DOIUrl":"https://doi.org/10.2147/tcrm.s326099","url":null,"abstract":"<strong>Abstract:</strong> Chronic hepatitis C (HCV) affects up to 3.25 million children and adolescents. Early treatment of HCV in children and adolescents reduces progression to advanced liver disease and cancer. Treatment for HCV has evolved to highly effective direct acting antiviral therapy in adults and now in children ≥ 3 years of age. This review focuses on the role of sofosbuvir and velpatasvir (SOF/VEL), a newer treatment of children and adolescents with chronic HCV. SOF/VEL is a pangenotypic DAA with primary clearance via the liver and biliary excretion. It has been studied in children and adolescents and is approved in the US for use in children and adolescents ≥ 3 years of age. Although the data are currently limited, SOF/VEL has demonstrated sustained viral response rates similar to comparable DAAs in the range of 95– 98%. To date, side effects have been minimal.<br/><br/><strong>Keywords:</strong> pediatric hepatitis C, pediatric hepatitis C treatment<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"62 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: This study aimed to rank the features that are important in terms of safety and effectiveness in choosing the surgical method and providing appropriate care to the patient by using the variables examined before and after the surgery to evaluate the success of mini percutaneous nephrolithotomy and standard percutaneous nephrolithotomy surgeries. Patients and Methods: The features evaluated before and after surgery were ranked according to their importance in the features considered, using Multivariate Adaptive Regression Splines (MARS), LASSO, Ridge, Elastic_net, and Random Forest algorithms as variable selection techniques. There are 278 samples in the relevant data set. Results: Type of surgery (100%), intercostal access (97.75%), kidney opening procedure (94.25%), postoperative creatinine (59.22%), hydronephrosis (52.23%), the number of entries (41.61%), and pre- and post-operative hemoglobin difference (45.13%) were determined as the most critical variables. The MARS algorithm showed the most successful performance, with the lowest mean absolute error (MAE) value of 0.3622, the lowest root mean square error (RMSE) value of 0.3960, and the highest R2 value of 0.3405. Conclusion: Clinical decision support systems can be helpful in eliminating errors and reducing costs. It can also improve the quality of healthcare and aid in the early diagnosis of diseases. Computer-aided decision-making systems can be developed using the results of such products. These systems can provide doctors with better information about their patient’s treatment options and improve decision-making. It can contribute to patients being better informed about the surgery results and taking an active role. In conclusion, this study provides essential information that should be included in the surgical decision-making process for patients using medications and with a history of percutaneous nephrolithotomy.
Keywords: digital decision in healthcare, percutaneous nephrolithotomy, surgery success, machine learning, MARS
{"title":"Mini Percutaneous Nephrolithotomy vs Standard Percutaneous Nephrolithotomy: A Perioperative Decision Support System for Surgical Success Comparison","authors":"Kerem Gencer","doi":"10.2147/tcrm.s444519","DOIUrl":"https://doi.org/10.2147/tcrm.s444519","url":null,"abstract":"<strong>Purpose:</strong> This study aimed to rank the features that are important in terms of safety and effectiveness in choosing the surgical method and providing appropriate care to the patient by using the variables examined before and after the surgery to evaluate the success of mini percutaneous nephrolithotomy and standard percutaneous nephrolithotomy surgeries.<br/><strong>Patients and Methods:</strong> The features evaluated before and after surgery were ranked according to their importance in the features considered, using Multivariate Adaptive Regression Splines (MARS), LASSO, Ridge, Elastic_net, and Random Forest algorithms as variable selection techniques. There are 278 samples in the relevant data set.<br/><strong>Results:</strong> Type of surgery (100%), intercostal access (97.75%), kidney opening procedure (94.25%), postoperative creatinine (59.22%), hydronephrosis (52.23%), the number of entries (41.61%), and pre- and post-operative hemoglobin difference (45.13%) were determined as the most critical variables. The MARS algorithm showed the most successful performance, with the lowest mean absolute error (MAE) value of 0.3622, the lowest root mean square error (RMSE) value of 0.3960, and the highest R<sup>2</sup> value of 0.3405.<br/><strong>Conclusion:</strong> Clinical decision support systems can be helpful in eliminating errors and reducing costs. It can also improve the quality of healthcare and aid in the early diagnosis of diseases. Computer-aided decision-making systems can be developed using the results of such products. These systems can provide doctors with better information about their patient’s treatment options and improve decision-making. It can contribute to patients being better informed about the surgery results and taking an active role. In conclusion, this study provides essential information that should be included in the surgical decision-making process for patients using medications and with a history of percutaneous nephrolithotomy.<br/><br/><strong>Keywords:</strong> digital decision in healthcare, percutaneous nephrolithotomy, surgery success, machine learning, MARS<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"32 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Systemic AL amyloidosis, a plasma cell dyscrasia, is characterized by the production of misfolded immunoglobulin light chain. These misfolded proteins aggregate into amyloid fibrils and deposit throughout the body, resulting in widespread organ dysfunction and ultimately death. Achieving rapid and maximal elimination of the plasma cell clone is crucial to long-term survival. Daratumumab, an anti-CD38 monoclonal antibody delivered intravenously, has been swiftly incorporated into standard first-line treatment regimens. A novel formulation of daratumumab has been developed that can be injected subcutaneously. Areas Covered: As a retrospective qualitative review of prior publications involving daratumumab, this work briefly summarizes the existing data regarding the safety and efficacy of subcutaneous (SC) daratumumab, compared to intravenous (IV) daratumumab. SC daratumumab appears to deliver the same disease benefit as IV daratumumab to patients with decreased infusion-related reactions (IRRs), decreased time for administration, and similar rates of adverse events (AEs) intrinsically related to daratumumab. Expert Opinion: SC daratumumab is preferred over IV daratumumab, but the clinical situation ultimately should determine route of administration. Further investigation into cost-effectiveness benefit is warranted.
Keywords: plasma cell dyscrasia, daratumumab, AL amyloidosis, adverse events, AE
简介系统性 AL 淀粉样变性是一种浆细胞发育不良症，其特征是产生折叠错误的免疫球蛋白轻链。这些错误折叠的蛋白质聚集成淀粉样纤维并沉积在全身，导致广泛的器官功能障碍，最终导致死亡。快速、最大限度地消除浆细胞克隆对长期生存至关重要。达拉单抗是一种静脉注射的抗CD38单克隆抗体，已被迅速纳入标准一线治疗方案。目前已开发出一种可皮下注射的新型达拉单抗制剂：作为对以前发表的涉及达拉单抗的文章的回顾性定性综述，本研究简要总结了与静脉注射达拉单抗相比，皮下注射达拉单抗的安全性和有效性方面的现有数据。皮下注射达拉单抗似乎能为患者带来与静脉注射达拉单抗相同的疾病获益，同时输液相关反应（IRRs）减少，用药时间缩短，与达拉单抗内在相关的不良事件（AEs）发生率相似：专家意见：与静脉注射达拉单抗相比，首选静脉注射达拉单抗，但最终应由临床情况决定给药途径。有必要进一步研究其成本效益。关键词：浆细胞异常、达拉单抗、AL 淀粉样变性、不良事件、AE
{"title":"Safety and Efficacy of Subcutaneous Daratumumab in Systemic AL Amyloidosis","authors":"Michael Sang Hughes, Suzanne Lentzsch","doi":"10.2147/tcrm.s325859","DOIUrl":"https://doi.org/10.2147/tcrm.s325859","url":null,"abstract":"<strong>Introduction:</strong> Systemic AL amyloidosis, a plasma cell dyscrasia, is characterized by the production of misfolded immunoglobulin light chain. These misfolded proteins aggregate into amyloid fibrils and deposit throughout the body, resulting in widespread organ dysfunction and ultimately death. Achieving rapid and maximal elimination of the plasma cell clone is crucial to long-term survival. Daratumumab, an anti-CD38 monoclonal antibody delivered intravenously, has been swiftly incorporated into standard first-line treatment regimens. A novel formulation of daratumumab has been developed that can be injected subcutaneously.<br/><strong>Areas Covered:</strong> As a retrospective qualitative review of prior publications involving daratumumab, this work briefly summarizes the existing data regarding the safety and efficacy of subcutaneous (SC) daratumumab, compared to intravenous (IV) daratumumab. SC daratumumab appears to deliver the same disease benefit as IV daratumumab to patients with decreased infusion-related reactions (IRRs), decreased time for administration, and similar rates of adverse events (AEs) intrinsically related to daratumumab.<br/><strong>Expert Opinion:</strong> SC daratumumab is preferred over IV daratumumab, but the clinical situation ultimately should determine route of administration. Further investigation into cost-effectiveness benefit is warranted. <br/><br/><strong>Keywords:</strong> plasma cell dyscrasia, daratumumab, AL amyloidosis, adverse events, AE<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"255 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chang Tang, Lanting Wang, Zihua Chen, Jin Yang, Haiqing Gao, Chenggong Guan, Qiaozhi Gu, Shan He, Fanping Yang, Shengan Chen, Li Ma, Zhen Zhang, Ying Zhao, Lin Tang, Yu Xu, Yue Hu, Xiaoqun Luo
Purpose: Several in vivo experiments have shown that molecular hydrogen is a promising therapeutic agent for interstitial lung diseases (ILD). In this study, hydrogen therapy was investigated to determine whether it is superior to N-Acetylcysteine (NAC) for the treatment of patients with early-stage ILD. Patients and Methods: A prospective, single-center, randomized, controlled clinical trial was conducted in 87 patients with early-stage ILD. Hydrogen or NAC therapy was randomly assigned (1:1 ratio) to the eligible patients. The primary endpoint was the change in the high-resolution computed tomography (HRCT) and composite physiologic index (CPI) scores from baseline to week 48. Pulmonary function was evaluated as a secondary endpoint, and adverse events were recorded for safety analysis. Results: The rate of HRCT image improvement from the baseline in the HW group (63.6%) was higher than that in the NAC group (39.5%). A significant decrease in CPI and improvement in DLCO-sb were observed in the hydrogen group compared with those in the control group. Changes in other pulmonary function parameters, including FVC, FEV1, FEV1/FVC%, and TLC, were not significantly different between the two groups. Adverse events were reported in 7 (15.9%) patients in the HW group and 10 (23.3%) patients in the NAC group, but the difference was not significant (P=0.706). Conclusion: Hydrogen therapy exhibits superior efficacy and acceptable safety compared with NAC therapy in patients with early-stage ILD.
{"title":"Efficacy and Safety of Hydrogen Therapy in Patients with Early-Stage Interstitial Lung Disease: A Single-Center, Randomized, Parallel-Group Controlled Trial","authors":"Chang Tang, Lanting Wang, Zihua Chen, Jin Yang, Haiqing Gao, Chenggong Guan, Qiaozhi Gu, Shan He, Fanping Yang, Shengan Chen, Li Ma, Zhen Zhang, Ying Zhao, Lin Tang, Yu Xu, Yue Hu, Xiaoqun Luo","doi":"10.2147/tcrm.s438044","DOIUrl":"https://doi.org/10.2147/tcrm.s438044","url":null,"abstract":"<strong>Purpose:</strong> Several in vivo experiments have shown that molecular hydrogen is a promising therapeutic agent for interstitial lung diseases (ILD). In this study, hydrogen therapy was investigated to determine whether it is superior to N-Acetylcysteine (NAC) for the treatment of patients with early-stage ILD.<br/><strong>Patients and Methods:</strong> A prospective, single-center, randomized, controlled clinical trial was conducted in 87 patients with early-stage ILD. Hydrogen or NAC therapy was randomly assigned (1:1 ratio) to the eligible patients. The primary endpoint was the change in the high-resolution computed tomography (HRCT) and composite physiologic index (CPI) scores from baseline to week 48. Pulmonary function was evaluated as a secondary endpoint, and adverse events were recorded for safety analysis.<br/><strong>Results:</strong> The rate of HRCT image improvement from the baseline in the HW group (63.6%) was higher than that in the NAC group (39.5%). A significant decrease in CPI and improvement in D<sub>L</sub>CO-sb were observed in the hydrogen group compared with those in the control group. Changes in other pulmonary function parameters, including FVC, FEV<sub>1</sub>, FEV<sub>1</sub>/FVC%, and TLC, were not significantly different between the two groups. Adverse events were reported in 7 (15.9%) patients in the HW group and 10 (23.3%) patients in the NAC group, but the difference was not significant (<em>P</em>=0.706).<br/><strong>Conclusion:</strong> Hydrogen therapy exhibits superior efficacy and acceptable safety compared with NAC therapy in patients with early-stage ILD.<br/><br/><strong>Keywords:</strong> hydrogen, N-acetylcysteine, interstitial lung disease, therapeutic effects<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"61 4 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138567046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: For the diagnosis of pediatric osteomyelitis, the sensitivity, specificity, and predictive value of erythrocyte sedimentation rate (ESR) were evaluated in this study. Methods: A systematic computer-based search was performed for relevant articles focusing on the ESR diagnosis of pediatric osteomyelitis in PubMed, Embase, and the Cochrane Library with an inclusion criteria: 1) the diagnostic utility of ESR for diagnosing osteomyelitis patients under the age of 18;2) two-by-two contingency tables can be obtained. Case reports, review papers, and animal experiments were excluded. Results: The diagnostic meta-analysis included 8 studies involving 348 children with osteomyelitis, all of whom were tested for ESR. Diagnostic meta-analysis revealed a sensitivity and specificity of 0.90, 95% confidence interval (CI) (0.86– 0.93), and 0.50 (95% CI,0.47– 0.54) for ESR in pediatric osteomyelitis diagnosis, respectively. The positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 1.38,(95% CI,1.08– 1.78), 0.46, (95% CI,0.26– 0.73), and 3.20, (95% CI,1.33– 7.69), respectively. The area under the curve (AUC) was determined to be 0.80 based on the summary receiver operating characteristic curve (SROC). Conclusion: The literature on the use of ESR in pediatric osteomyelitis diagnosis was thoroughly reviewed in this study. It was also found that ESR may be useful as a biomarker for pediatric osteomyelitis diagnosis. Due to its low specificity, it should be used in combination with other markers such as C-reactive protein, neutrophil percentage, and white blood cell count.
{"title":"Erythrocyte Sedimentation Rate for Assisted Diagnosis of Pediatric Osteomyelitis: A Meta-Analysis","authors":"Han Qi, Zhitao Zhu, Dongsheng Zhu","doi":"10.2147/tcrm.s440996","DOIUrl":"https://doi.org/10.2147/tcrm.s440996","url":null,"abstract":"<strong>Objective:</strong> For the diagnosis of pediatric osteomyelitis, the sensitivity, specificity, and predictive value of erythrocyte sedimentation rate (ESR) were evaluated in this study.<br/><strong>Methods:</strong> A systematic computer-based search was performed for relevant articles focusing on the ESR diagnosis of pediatric osteomyelitis in PubMed, Embase, and the Cochrane Library with an inclusion criteria: 1) the diagnostic utility of ESR for diagnosing osteomyelitis patients under the age of 18;2) two-by-two contingency tables can be obtained. Case reports, review papers, and animal experiments were excluded.<br/><strong>Results:</strong> The diagnostic meta-analysis included 8 studies involving 348 children with osteomyelitis, all of whom were tested for ESR. Diagnostic meta-analysis revealed a sensitivity and specificity of 0.90, 95% confidence interval (CI) (0.86– 0.93), and 0.50 (95% CI,0.47– 0.54) for ESR in pediatric osteomyelitis diagnosis, respectively. The positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 1.38,(95% CI,1.08– 1.78), 0.46, (95% CI,0.26– 0.73), and 3.20, (95% CI,1.33– 7.69), respectively. The area under the curve (AUC) was determined to be 0.80 based on the summary receiver operating characteristic curve (SROC).<br/><strong>Conclusion:</strong> The literature on the use of ESR in pediatric osteomyelitis diagnosis was thoroughly reviewed in this study. It was also found that ESR may be useful as a biomarker for pediatric osteomyelitis diagnosis. Due to its low specificity, it should be used in combination with other markers such as C-reactive protein, neutrophil percentage, and white blood cell count.<br/><br/><strong>Keywords:</strong> osteomyelitis, pediatric, ESR, diagnosis, meta-analysis<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138548266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The Ramathibodi Rapid Response System (RRRS), implemented in March 2017, aims to identify and respond to patients with deteriorating conditions outside the ICU. It employs the Ramathibodi early warning score and clinical signs to monitor all admitted patients, providing expert physician monitoring and early treatment for stabilization and appropriate care triage. This study assesses the RRRS’s effectiveness in reducing in-hospital mortality and CPR events outside the ICU. Patients and Methods: We conducted a retrospective observational study from March 2014 to February 2020 in a tertiary care hospital’s general wards. We included adult patients experiencing unplanned ICU admission, sudden cardiac arrest, or unexpected death. The study compared in-hospital mortality and CPR incidence outside the ICU between pre- and post-RRRS implementation groups. The associations between RRRS implementation and in-hospital mortality and the incidence of CPR outside the ICU were assessed using multiple logistic regression analyses. Results: We evaluated 17,741 admissions, with 9168 before RRRS implementation (1 March 2014 to 28 February 2017) and 8573 after RRRS implementation (1 March 2017 to 29 February 2020). The implementation of RRRS was associated with a significant reduction in in-hospital mortality, which decreased from 30.0% to 20.8% (odds ratio, 0.62; 95% confidence interval [CI], 0.57 to 0.66; P< 0.0001). Even after adjusting for age, sex, and comorbidities, the reduction in in-hospital mortality remained significant (adjusted odds ratio, 0.58; 95% CI, 0.54 to 0.63; P< 0.0001). The incidence of CPR outside the ICU also decreased from 1.8% to 1.1% (adjusted odds ratio, 0.6; 95% CI, 0.46 to 0.77; P< 0.0001). Additionally, the rate of ICU transfer increased from 85.4% to 92.1% (risk difference, 6.7; 95% CI, 7.6 to 5.8; P< 0.0001) after implementing the RRRS. Conclusion: Implementing the RRRS is associated with a reduction in in-hospital mortality and the incidence of CPR outside the ICU.
Keywords: rapid response system, rapid response team, deteriorating patient, in-hospital mortality, cardiopulmonary resuscitation, intensive care unit, implementation protocol
{"title":"Effect of the Ramathibodi Rapid Response System Triggered by the Ramathibodi Early Warning Score and Clinical Warning Signs on in-Hospital Mortality and the Incidence of Cardiopulmonary Resuscitation in Adult Hospitalized Patients","authors":"Chutipong Kwantong, Yuda Sutherasan, Detajin Junhasavasdikul, Tananchai Petnak, Pongdhep Theerawit","doi":"10.2147/tcrm.s426061","DOIUrl":"https://doi.org/10.2147/tcrm.s426061","url":null,"abstract":"<strong>Purpose:</strong> The Ramathibodi Rapid Response System (RRRS), implemented in March 2017, aims to identify and respond to patients with deteriorating conditions outside the ICU. It employs the Ramathibodi early warning score and clinical signs to monitor all admitted patients, providing expert physician monitoring and early treatment for stabilization and appropriate care triage. This study assesses the RRRS’s effectiveness in reducing in-hospital mortality and CPR events outside the ICU.<br/><strong>Patients and Methods:</strong> We conducted a retrospective observational study from March 2014 to February 2020 in a tertiary care hospital’s general wards. We included adult patients experiencing unplanned ICU admission, sudden cardiac arrest, or unexpected death. The study compared in-hospital mortality and CPR incidence outside the ICU between pre- and post-RRRS implementation groups. The associations between RRRS implementation and in-hospital mortality and the incidence of CPR outside the ICU were assessed using multiple logistic regression analyses.<br/><strong>Results:</strong> We evaluated 17,741 admissions, with 9168 before RRRS implementation (1 March 2014 to 28 February 2017) and 8573 after RRRS implementation (1 March 2017 to 29 February 2020). The implementation of RRRS was associated with a significant reduction in in-hospital mortality, which decreased from 30.0% to 20.8% (odds ratio, 0.62; 95% confidence interval [CI], 0.57 to 0.66; P< 0.0001). Even after adjusting for age, sex, and comorbidities, the reduction in in-hospital mortality remained significant (adjusted odds ratio, 0.58; 95% CI, 0.54 to 0.63; P< 0.0001). The incidence of CPR outside the ICU also decreased from 1.8% to 1.1% (adjusted odds ratio, 0.6; 95% CI, 0.46 to 0.77; P< 0.0001). Additionally, the rate of ICU transfer increased from 85.4% to 92.1% (risk difference, 6.7; 95% CI, 7.6 to 5.8; P< 0.0001) after implementing the RRRS.<br/><strong>Conclusion:</strong> Implementing the RRRS is associated with a reduction in in-hospital mortality and the incidence of CPR outside the ICU.<br/><br/><strong>Keywords:</strong> rapid response system, rapid response team, deteriorating patient, in-hospital mortality, cardiopulmonary resuscitation, intensive care unit, implementation protocol<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"18 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138512489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract: Deutetrabenazine (DTBZ) is used for the treatment of tardive dyskinesia (TD) and chorea in Huntington’s Disease (HD). Four pivotal clinical trials showed the efficacy of DTBZ in these conditions. Long term follow-up studies confirmed evidence of overall safety and continued efficacy of this drug. Indirect comparisons revealed relative superiority of DTBZ over TBZ in terms of safety, but direct comparisons of safety and efficacy between the VMAT2 and dopamine blocking agents is lacking. Deutetrabenazine is safe and effective in the treatment of TD and chorea in HD in doses up to 72 mg daily and for up to three years in duration.
Keywords: chorea, tardive dyskinesia, hyperkinetic movement disorders, VMAT2 inhibitors
{"title":"Clinical Utility of Deutetrabenazine as a Treatment Option for Chorea Associated with Huntington’s Disease and Tardive Dyskinesia","authors":"Samuel Frank, Aljoharah Alakkas","doi":"10.2147/tcrm.s279332","DOIUrl":"https://doi.org/10.2147/tcrm.s279332","url":null,"abstract":"<strong>Abstract:</strong> Deutetrabenazine (DTBZ) is used for the treatment of tardive dyskinesia (TD) and chorea in Huntington’s Disease (HD). Four pivotal clinical trials showed the efficacy of DTBZ in these conditions. Long term follow-up studies confirmed evidence of overall safety and continued efficacy of this drug. Indirect comparisons revealed relative superiority of DTBZ over TBZ in terms of safety, but direct comparisons of safety and efficacy between the VMAT2 and dopamine blocking agents is lacking. Deutetrabenazine is safe and effective in the treatment of TD and chorea in HD in doses up to 72 mg daily and for up to three years in duration.<br/><br/><strong>Keywords:</strong> chorea, tardive dyskinesia, hyperkinetic movement disorders, VMAT2 inhibitors<br/>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"19 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138512477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-29eCollection Date: 2023-01-01DOI: 10.2147/TCRM.S432856
Jennifer Gallardo-Cóndor, Pablo Naranjo, Sebastián Atarihuana, Dayana Coello, Patricia Guevara-Ramírez, Rodrigo Flores-Espinoza, Germán Burgos, Andrés López-Cortés, Alejandro Cabrera-Andrade
Purpose: Thiopurine S-methyltransferase (TPMT) is an enzyme that metabolizes purine analogs, agents used in the treatment of acute lymphoblastic leukemia. Improper drug metabolism leads to toxicity in chemotherapy patients and reduces treatment effectiveness. TPMT variants associated with reduced enzymatic activity vary across populations. Therefore, studying these variants in heterogeneous populations, such as Ecuadorians, can help identify molecular causes of deficiency for this enzyme.
Methods: We sequenced the entire TPMT coding region in 550 Ecuadorian individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnicities. Moreover, we conducted an ancestry analysis using 46 informative ancestry markers.
Results: We identified 8 single nucleotide variants in the coding region of TPMT. The most prevalent alleles were TPMT*3A, TPMT*3B, and TPMT*3C, with frequencies of 0.055, 0.012, and 0.015, respectively. Additionally, we found rare alleles TPMT*4 and TPMT*8 with frequencies of 0.005 and 0.003. Correlating the ancestry proportions with TPMT-deficient genotypes, we observed that the Native American ancestry proportion influenced the distribution of the TPMT*1/TPMT*3A genotype (OR = 5.977, p = 0.002), while the contribution of African ancestral populations was associated with the TPMT*1/TPMT*3C genotype (OR = 9.769, p = 0.003). The rates of TPMT-deficient genotypes observed in Mestizo (f = 0.121) and Indigenous (f = 0.273) groups provide evidence for the influence of Native American ancestry and the prevalence of the TPMT*3A allele. In contrast, although Afro-Ecuadorian groups demonstrate similar deficiency rates (f = 0.160), the genetic factors involved are associated with contributions from African ancestral populations, specifically the prevalent TPMT*3C allele.
Conclusion: The distribution of TPMT-deficient variants offers valuable insights into the populations under study, underscoring the necessity for genetic screening strategies to prevent thiopurine toxicity events among Latin American minority groups.
目的:硫嘌呤s -甲基转移酶(TPMT)是一种代谢嘌呤类似物的酶，嘌呤类似物用于治疗急性淋巴细胞白血病。药物代谢不良导致化疗患者出现毒性，降低治疗效果。与酶活性降低相关的TPMT变异因人群而异。因此，在异质人群中研究这些变异，如厄瓜多尔人，可以帮助确定这种酶缺乏的分子原因。方法:我们对来自非裔厄瓜多尔人、土著、梅斯蒂索人和蒙特比奥种族的550名厄瓜多尔人的整个TPMT编码区进行了测序。此外，我们使用46个信息性祖先标记进行了祖先分析。结果:我们在TPMT编码区鉴定出8个单核苷酸变异。最常见的等位基因为TPMT*3A、TPMT*3B和TPMT*3C，频率分别为0.055、0.012和0.015。此外，我们发现罕见的等位基因TPMT*4和TPMT*8的频率分别为0.005和0.003。将祖先比例与TPMT缺陷基因型相关联，我们发现美洲原住民祖先比例影响TPMT*1/TPMT*3A基因型的分布(OR = 5.977, p = 0.002)，而非洲祖先群体的贡献与TPMT*1/TPMT*3C基因型相关(OR = 9.769, p = 0.003)。在混血儿(f = 0.121)和土著(f = 0.273)群体中观察到的TPMT基因型缺陷率为美洲土著血统的影响和TPMT*3A等位基因的流行提供了证据。相比之下，尽管非裔厄瓜多尔人群体显示出相似的缺乏率(f = 0.160)，但所涉及的遗传因素与非洲祖先人群的贡献有关，特别是普遍存在的TPMT*3C等位基因。结论:tpmt缺陷变异的分布为研究人群提供了有价值的见解，强调了在拉丁美洲少数群体中进行遗传筛查以预防硫嘌呤毒性事件的必要性。
{"title":"Population-Specific Distribution of <i>TPMT</i> Deficiency Variants and Ancestry Proportions in Ecuadorian Ethnic Groups: Towards Personalized Medicine.","authors":"Jennifer Gallardo-Cóndor, Pablo Naranjo, Sebastián Atarihuana, Dayana Coello, Patricia Guevara-Ramírez, Rodrigo Flores-Espinoza, Germán Burgos, Andrés López-Cortés, Alejandro Cabrera-Andrade","doi":"10.2147/TCRM.S432856","DOIUrl":"10.2147/TCRM.S432856","url":null,"abstract":"<p><strong>Purpose: </strong>Thiopurine S-methyltransferase (TPMT) is an enzyme that metabolizes purine analogs, agents used in the treatment of acute lymphoblastic leukemia. Improper drug metabolism leads to toxicity in chemotherapy patients and reduces treatment effectiveness. <i>TPMT</i> variants associated with reduced enzymatic activity vary across populations. Therefore, studying these variants in heterogeneous populations, such as Ecuadorians, can help identify molecular causes of deficiency for this enzyme.</p><p><strong>Methods: </strong>We sequenced the entire <i>TPMT</i> coding region in 550 Ecuadorian individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnicities. Moreover, we conducted an ancestry analysis using 46 informative ancestry markers.</p><p><strong>Results: </strong>We identified 8 single nucleotide variants in the coding region of <i>TPMT</i>. The most prevalent alleles were <i>TPMT*3A, TPMT*3B</i>, and <i>TPMT*3C</i>, with frequencies of 0.055, 0.012, and 0.015, respectively. Additionally, we found rare alleles <i>TPMT*4</i> and <i>TPMT*8</i> with frequencies of 0.005 and 0.003. Correlating the ancestry proportions with <i>TPMT</i>-deficient genotypes, we observed that the Native American ancestry proportion influenced the distribution of the <i>TPMT*1/TPMT*3A</i> genotype (OR = 5.977, p = 0.002), while the contribution of African ancestral populations was associated with the <i>TPMT*1/TPMT*3C</i> genotype (OR = 9.769, p = 0.003). The rates of TPMT-deficient genotypes observed in Mestizo (<i>f</i> = 0.121) and Indigenous (<i>f</i> = 0.273) groups provide evidence for the influence of Native American ancestry and the prevalence of the <i>TPMT*3A</i> allele. In contrast, although Afro-Ecuadorian groups demonstrate similar deficiency rates (<i>f</i> = 0.160), the genetic factors involved are associated with contributions from African ancestral populations, specifically the prevalent <i>TPMT*3C</i> allele.</p><p><strong>Conclusion: </strong>The distribution of TPMT-deficient variants offers valuable insights into the populations under study, underscoring the necessity for genetic screening strategies to prevent thiopurine toxicity events among Latin American minority groups.</p>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"19 ","pages":"1005-1018"},"PeriodicalIF":2.8,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138483004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aimed to create and validate a novel nomogram to predict the risk of symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT).
Methods: In this retrospective study, 784 patients with AIS who received IVT were enrolled. The patients were randomly divided into two groups: a training set (n=550, 70%) and a testing set (n=234, 30%). Utilizing multivariable logistic regression analysis, relevant factors for the predictive nomogram were selected. The performance of the nomogram was evaluated using various metrics, including the area under the receiver operating characteristic curve (AUC-ROC), the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA).
Results: Multivariable logistic regression analysis showed that specific factors, including National Institutes of Health Stroke Scale (NIHSS) scores, Early infarct signs (EIS), and serum sodium, were identified as independent predictors of sICH. Subsequently, a nomogram was constructed using these predictors. The AUC-ROC values of the nomogram were 0.864 (95% CI: 0.810-0.919) and 0.831 (95% CI: 0.770-0.891) in the training and the validation sets, respectively. Both the calibration plots and the Hosmer-Lemeshow goodness-of-fit test showed favorable agreement in both the training and the validation sets. Additionally, the DCA indicated the practical clinical utility of the nomogram.
Conclusion: The novel nomogram, which included NIHSS, EIS and serum sodium as variables, had the potential for predicting the risk of sICH in patients with AIS after IVT.
{"title":"A Novel Nomogram to Predict Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients After Intravenous Thrombolysis.","authors":"Zhuangzhuang Jiang, Dongjuan Xu, Hongfei Li, Xiaolan Wu","doi":"10.2147/TCRM.S436145","DOIUrl":"10.2147/TCRM.S436145","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to create and validate a novel nomogram to predict the risk of symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT).</p><p><strong>Methods: </strong>In this retrospective study, 784 patients with AIS who received IVT were enrolled. The patients were randomly divided into two groups: a training set (n=550, 70%) and a testing set (n=234, 30%). Utilizing multivariable logistic regression analysis, relevant factors for the predictive nomogram were selected. The performance of the nomogram was evaluated using various metrics, including the area under the receiver operating characteristic curve (AUC-ROC), the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Multivariable logistic regression analysis showed that specific factors, including National Institutes of Health Stroke Scale (NIHSS) scores, Early infarct signs (EIS), and serum sodium, were identified as independent predictors of sICH. Subsequently, a nomogram was constructed using these predictors. The AUC-ROC values of the nomogram were 0.864 (95% CI: 0.810-0.919) and 0.831 (95% CI: 0.770-0.891) in the training and the validation sets, respectively. Both the calibration plots and the Hosmer-Lemeshow goodness-of-fit test showed favorable agreement in both the training and the validation sets. Additionally, the DCA indicated the practical clinical utility of the nomogram.</p><p><strong>Conclusion: </strong>The novel nomogram, which included NIHSS, EIS and serum sodium as variables, had the potential for predicting the risk of sICH in patients with AIS after IVT.</p>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"19 ","pages":"993-1003"},"PeriodicalIF":2.8,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138483003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27eCollection Date: 2023-01-01DOI: 10.2147/TCRM.S361706
Stacy Dixon, Xuan Kang, Dianna Quan
Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited genetic disorder that affects 5000-10,000 people worldwide. It is caused by mutations in the transthyretin (TTR) gene and results in amyloid deposition in a variety of organs due to abnormal accumulation of TTR protein fibrils. Although this is a multisystem disorder, the heart and peripheral nerves are the preferentially affected organs. Over 150 TTR gene mutations have been associated with this disease and the clinical phenotype can vary significantly. Severe forms of the disorder can be fatal. Fortunately, the oligonucleotide-based therapy era has resulted in the development of several novel treatment options. Patisiran is a small interfering RNA (siRNA) encapsulated in a lipid nanoparticle that targets both mutant and wild-type TTR and results in significant reductions of the TTR protein in the serum and in tissue deposits. Patisiran has been approved for treatment of adults with polyneuropathy due to hereditary TTR-mediated amyloidosis in both the United States (US) and European Union (EU). In this review, we will discuss the development of patisiran, the clinical trials that lead to treatment approval, and provide guideline parameters for use in clinical practice. .
{"title":"Practical Guidance for the Use of Patisiran in the Management of Polyneuropathy in Hereditary Transthyretin-Mediated Amyloidosis.","authors":"Stacy Dixon, Xuan Kang, Dianna Quan","doi":"10.2147/TCRM.S361706","DOIUrl":"10.2147/TCRM.S361706","url":null,"abstract":"<p><p>Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited genetic disorder that affects 5000-10,000 people worldwide. It is caused by mutations in the transthyretin (TTR) gene and results in amyloid deposition in a variety of organs due to abnormal accumulation of TTR protein fibrils. Although this is a multisystem disorder, the heart and peripheral nerves are the preferentially affected organs. Over 150 TTR gene mutations have been associated with this disease and the clinical phenotype can vary significantly. Severe forms of the disorder can be fatal. Fortunately, the oligonucleotide-based therapy era has resulted in the development of several novel treatment options. Patisiran is a small interfering RNA (siRNA) encapsulated in a lipid nanoparticle that targets both mutant and wild-type TTR and results in significant reductions of the TTR protein in the serum and in tissue deposits. Patisiran has been approved for treatment of adults with polyneuropathy due to hereditary TTR-mediated amyloidosis in both the United States (US) and European Union (EU). In this review, we will discuss the development of patisiran, the clinical trials that lead to treatment approval, and provide guideline parameters for use in clinical practice. .</p>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"19 ","pages":"973-981"},"PeriodicalIF":2.8,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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