Clinical therapeutics最新文献

{"title":"Correlation of Triethylamine N-oxide (TMAO), LPS, and TNF-Alpha Levels With Clinical Features of the Disease in Patients With and Without Septic Shock Infected With COVID-19 Virus.","authors":"Kübra Polat, Mehtap Gömleksiz, Kübra Oral, Nevzat Gözel, Gaweł Sołowski, Tugҫe Kaymaz, Mehmet Ferit Gürsu","doi":"10.1016/j.clinthera.2024.09.021","DOIUrl":"10.1016/j.clinthera.2024.09.021","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is a response of the immune system to protect the body against various diseases or injuries. Serum trimethylamine N-oxide (TMAO) levels may vary depending on age, gender, habits, comorbidities, and microbiota.</p><p><strong>Aims: </strong>In this study, we investigated whether TMAO levels have diagnostic significance and their potential as a marker in the early diagnosis of the disease. Another aim of the research was to identify changes in TMAO levels as a reflection of the deterioration in the microflora, and IL-6, IL-10, IL-1β, TNF-alpha, and LPS levels in patient groups. Then, we recognized relationships between these parameters in patients infected with COVID-19 without septic shock and with COVID-19 who were without transmission of COVID-19 in septic shock.</p><p><strong>Study design: </strong>A total of 160 patients were investigated, including 40 patients infected with COVID-19 without septic contact, 40 patients with COVID-19 positive septic shock, 40 patients with COVID-19 negative septic shock, and 40 healthy individuals as the control group.</p><p><strong>Results: </strong>TNF-α and IL-1β levels were significantly lower (P < 0.001) and IL-6 and IL-10 levels were significantly higher (P < 0.001) in patient groups than in control groups. IL-1β showed a significant decrease, especially in the groups infected with COVID-19. Although IL-6, increased even more in the groups infected with COVID-19.</p><p><strong>Conclusions: </strong>LPS level was remarkably high in the sepsis group infected with COVID-19 compared to the other groups. TMAO level was significantly higher (P < 0.001) in the sepsis group. Therefore, TMAO is a potential biomarker in sepsis and septic shock.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":"e1-e8"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Enrolling Pregnant Persons Into Acute Care Clinical Trials, A Discussion With the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP) Trial Principal Investigators.","authors":"Sarah M Perman, William Meurer, Robert Silbergleit, Angela F Jarman","doi":"10.1016/j.clinthera.2024.11.006","DOIUrl":"10.1016/j.clinthera.2024.11.006","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":"945-948"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-Way Randomized Crossover Study to Establish Pharmacodynamic Bioequivalence Between Oxylanthanum Carbonate and Lanthanum Carbonate.","authors":"Vandana Mathur, Michael Walker, Steve Hasal, Guru Reddy, Shalabh Gupta","doi":"10.1016/j.clinthera.2024.11.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.11.009","url":null,"abstract":"<p><strong>Purpose: </strong>Phosphate binders (PB) are integral to hyperphosphatemia management in patients with end-stage kidney disease. PB efficacy is adversely affected by nonadherence and limited phosphate-binding capacity relative to dietary intake. Oxylanthanum carbonate is an investigational novel nanotechnology product that combines lanthanum, which has the highest binding capacity of available PBs, with a smaller pill size that is swallowed with water rather than chewed. This study's objective was to demonstrate the pharmacodynamic equivalence of orally administered oxylanthanum carbonate to lanthanum carbonate (LC) in healthy subjects.</p><p><strong>Methods: </strong>In this phase one, single-center, randomized, open-label study, healthy subjects were treated with oxylanthanum carbonate swallowable tablets 1000 mg three times/day and LC chewable tablets 1000 mg three times/day in a two-way crossover design. The primary pharmacodynamic variable was the least squares mean (LSM) change in urinary phosphate excretion from baseline to the evaluation period (Days 1-4 of treatment).</p><p><strong>Findings: </strong>A total of 80 subjects were randomized and 75 received all doses. The LSM change in urinary phosphate excretion from Baseline to the Evaluation (Treatment) Period was similar for both oxylanthanum carbonate (-320.4 mg/day [90% CI: -349.7, -291.0]) and LC (-324.0 mg/day [90% CI: -353.3, -294.7]); the between-group LSM difference was 3.6 [90% CI: -37.8, 45.1] mg/day. Both drugs were well tolerated with an equal incidence of adverse events.</p><p><strong>Implications: </strong>Thus, oxylanthanum carbonate was bioequivalent to LC in healthy subjects and well tolerated. Oral oxylanthanum carbonate may provide an option for patients with chronic kidney disease and hyperphosphatemia for whom chewing tablets is disliked, inconvenient, or difficult.</p><p><strong>Clinical trial registration number: </strong>NCT06218290.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor, Regarding \"Optimizing Acute Ischemic Stroke Outcomes: The Role of Tenecteplase Before Mechanical Thrombectomy\" Recently Published by Ketabforoush and Colleagues.","authors":"Senta Frol, René Chapot","doi":"10.1016/j.clinthera.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.11.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inappropriate Prescribing of Nirmatrelvir/Ritonavir in Solid Organ Transplantation With COVID-19 Infection: A Multicenter Retrospective Study.","authors":"Ying Zhang, Kuifen Ma, Wenjing Hou, Xiangduan Liu, Jiaojiao Chen, Ying Wang, Ying Zhu, Qing Qian, Zhuoling An, Hui Yang","doi":"10.1016/j.clinthera.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.10.013","url":null,"abstract":"<p><strong>Background: </strong>Nirmatrelvir-ritonavir (NR) has demonstrated effectiveness in halting the progression to severe coronavirus disease 2019 (COVID-19) among solid organ transplant recipients (SOTRs) infected with Severe Acute Respiratory Syndrome Coronavirus 2. However, it has a wide range of interactions, especially with immunosuppressants. The study aimed to comprehensively evaluate the Inappropriate prescribing of NR and immunosuppressants in SOTRs with COVID-19, while also highlighting the essential aspects.</p><p><strong>Methods: </strong>We included hospitalized SOTRs who received NR at five tertiary hospitals between December 2022 and June 2023, and evaluated their prescription.</p><p><strong>Results: </strong>A total of 211 patients were enrolled, of which 205 did not meet all criteria for appropriate prescribing (97.16%). Inappropriateness primarily stemmed from starting treatment more than 5 days after symptom onset (87.68%), followed by application in severe-to-critical cases of COVID-19 (52.13%), the inappropriate dosages based on renal function (47.87%). Contraindications encompassed 17.06% of patients with severe renal impairment and 5.69% with contraindicated drug interactions. Inappropriate resumption of immunosuppressants accounted for a larger proportion than inappropriate discontinuation or dose adjustment (30.16% vs 8.99%). More than one-third of patients neglected to monitor concentrations. About 8% experienced abnormal high concentrations.</p><p><strong>Conclusion: </strong>Inappropriate prescribing of NR is widespread among hospitalized SOTRs. Adjusting doses based on patients' renal function and paying attention to concurrent use of immunosuppressive drugs are crucial, and therapeutic drug monitoring is necessary. Clinical practitioners should enhance their vigilance and attention.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world Evidence on Oral Semaglutide for the Management of Type 2 Diabetes. A Narrative Review for Clinical Practice.","authors":"M Marassi, G P Fadini","doi":"10.1016/j.clinthera.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.11.005","url":null,"abstract":"<p><strong>Purpose: </strong>Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) available for type 2 diabetes mellitus (T2DM) management, whose effectiveness and tolerability have extensively been demonstrated in the PIONEER clinical trial program. Nevertheless, data from real-world are crucial to evaluate treatment performance under routine care. The aim of this narrative review is to summarize available evidence regarding real-world utilization patterns of oral semaglutide, and discuss efficacy, safety, and dosing regimen data in routine scenarios.</p><p><strong>Methods: </strong>We searched PubMed for real-world studies evaluating oral semaglutide up to August 2024, and specific search terms were: \"oral semaglutide,\" and \"real-world studies\" or \"observational studies\" or \"retrospective studies\".</p><p><strong>Findings: </strong>19 real-world studies were included in the narrative review. In real-world settings, oral semaglutide provided significant glycemic (median HbA1c reduction at 6 months of 1%) and weight (median body weight reduction of 2 to 3 kg) benefits across the spectrum of T2DM, aligning with pre-clinical evidence from the PIONEER program. No new tolerability and safety issue has emerged from oral semaglutide administration in routine clinical practice.</p><p><strong>Implications: </strong>Oral semaglutide constitutes an effective and safe option for T2DM management, and its increased acceptance has the potential to favor the early introduction of GLP-1RAs along the disease course. Nevertheless, continuous evaluation of real-world data is critical to better define the optimal positioning of oral semaglutide along T2DM trajectory and fully exploit its potential in everyday clinical practice.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: \"Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients\" [Clin Ther 2024;46:778-784].","authors":"Essy Mozaffari, Aastha Chandak, Andrew Ustianowski, Christina G Rivera, Neera Ahuja, Heng Jiang, Mark Berry, Jason F Okulicz, Alpesh N Amin","doi":"10.1016/j.clinthera.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.11.013","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Pancreatitis and Pancreatic Cancer Risk Among Patients With Type 2 Diabetes Receiving Dipeptidyl Peptidase 4 Inhibitors: An Updated Meta-Analysis of Randomized Controlled Trials\" [Clinical Therapeutics 2024 Aug;46(8):650-656/CLINTHER-D-24-00055R1].","authors":"Adili Tuersun, Guanxin Hou, Gang Cheng","doi":"10.1016/j.clinthera.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.11.010","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors for INtubation-SURfactant-Extubation Failure in Infants With Neonatal Respiratory Distress Syndrome.","authors":"Haoming Chen, Qingfei Hao, Jing Zhang, Yanna Du, Hafiz Muhammad Sohail Sarwar, Jing Li, Tiantian Yang, Xiuyong Cheng","doi":"10.1016/j.clinthera.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.10.009","url":null,"abstract":"<p><strong>Purpose: </strong>To identify clinical characteristics predictive of failure or success of the INtubation-SURfactant-Extubation (INSURE) strategy, to distinguish infants who could be managed using this strategy to prevent mechanical ventilation (MV).</p><p><strong>Methods: </strong>Infants with a gestational age <32 weeks were classified into two groups according to whether they required reintubation and MV within 72 h after birth. The clinical characteristics of the two groups were subsequently analyzed.</p><p><strong>Results: </strong>INSURE was unsuccessful in 77 infants (20.7%). Infants in the INSURE failure group had a higher incidence of severe respiratory distress syndrome, as evidenced by radiological grade; lower blood pH, partial oxygen pressure, and base excess (BE) levels; higher partial carbon dioxide pressure levels at the first arterial blood gas analysis; lower Apgar scores at 1 and 5 min; lower use of antenatal steroids; and higher occurrence of gestational diabetes mellitus, versus those in the INSURE success group. Multiple regression analysis confirmed severe radiological grade, lower BE levels at the first arterial blood gas analysis, and decreased use of antenatal steroids as independent risk factors for INSURE failure. Compared with infants in the INSURE success group, those in the INSURE failure group also had higher mortality.</p><p><strong>Conclusions: </strong>We successfully identified specific predictors of an unsuccessful INSURE strategy. Maintaining high-risk preterm infants with one or several predictors intubated and treated with MV after surfactant administration can prevent reintubation and reduce mortality.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy Research of Prophylactic PEG-rhG-CSF in Preventing Neutropenia in Early-Stage Breast Cancer Patients Treated With Docetaxel-Based Chemotherapy: A Retrospective Analysis.","authors":"Xueting Xing, Weijie Ding, Yongzhe Tang, Jin Zhang, Yamin Liu, Junhong Ning, Jie Wang, Xiaoqing Zhang","doi":"10.1016/j.clinthera.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.10.006","url":null,"abstract":"<p><strong>Purpose: </strong>Docetaxel-based chemotherapy regimens (DBRs) are commonly used in the treatment of early-stage breast cancer (EBC). The prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) has been shown to reduce the incidence of neutropenia induced by DBRs. However, the clinical usage of PEG-rhG-CSF in EBC patients undergoing DBRs in China remains unclear.</p><p><strong>Methods: </strong>This retrospective study was conducted in 137 EBC patients receiving DBRs from September 2022 to February 2024. We compared the incidence of chemotherapy-induced neutropenia (CIN) between patients who was treated with prophylactic PEG-rhG-CSF or not by complete blood counts, evaluating the effectiveness of PEG-rhG-CSF in preventing CIN. Prophylactic PEG-rhG-CSF was given at 100 μg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy. Meanwhile, we also collected basic patient information, the area under time-concentration curve of docetaxel, and liver and kidney function indicators. Multivariate logistic regression and Receiver operating characteristic (ROC) curve analysis were employed to explore independent factors influencing neutropenia.</p><p><strong>Findings: </strong>In this study, 87 of 137 EBC patients were administrated with prophylactic PEG-rhG-CSF, while 50 were not. Compared to patients who did not receive PEG-rhG-CSF, those who received prophylactic injections had a significantly lower incidence of grade 3-4 CIN (20% vs. 4.6%, P < 0.05). Higher body surface area (BSA), lower body mass index (BMI), elevated alanine aminotransferase (ALT), and nonprophylactic use of PEG-rhG-CSF were found to be positively correlated with CIN occurrence. ROC curve analysis indicated an area under the curve of 0.756 for predicting CIN in EBC patients when BSA was 1.66 m², BMI was 24.8 kg/m², and ALT was 41 U/L, with a sensitivity of 73.08% and specificity of 73.87%.</p><p><strong>Implications: </strong>Prophylactic use of PEG-rhG-CSF significantly reduces the incidence of CIN, particularly grades 3 and 4. BSA, BMI, ALT, and PEG-rhG-CSF prophylaxis are independent influencing factors for the occurrence of neutropenia.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616382","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}