Clinical therapeutics最新文献

{"title":"Successful Subcutaneous Immunoglobulin Therapy in a Case Series of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","authors":"","doi":"10.1016/j.clinthera.2024.05.010","DOIUrl":"10.1016/j.clinthera.2024.05.010","url":null,"abstract":"<div><h3>Purpose</h3><p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains an enigma with no curable treatment options at hand. Although patients with ME/CFS are a heterogeneous group, a large proportion of patients present with an infection-driven symptomatology, making them potential responders to immunologic treatments, such as immunoglobulin (IG). Previous studies on IG treatment in patients with ME/CFS have not been consistent but have described beneficial effects in subgroups of patients.</p></div><div><h3>Methods</h3><p>Here we present data on a series of cases (n = 17) with infection-related ME/CFS (as defined by disease history and ongoing recurrent infections) treated with subcutaneous low-dose IG (0.06 g/kg/mo) over 5 weeks with continuous monitoring of symptoms.</p></div><div><h3>Findings</h3><p>Patients were predominantly female (65%) with mild-to-moderate disease severity (82%) and with poor self-reported quality of life (median, 25 on a 0–100 scale) and working ability (median, 5 on a 0–100 scale) before treatment. After 5 weeks of treatment with low-dose IG, significant improvements in symptoms, quality of life, and working ability were noted (all <em>P</em> &lt; 0.05). Among the 7 patients who reported the highest benefit of the treatment, quality of life increased by 35 units (on a 0–100 scale), with 1 patient reporting complete elimination of ME/CFS symptoms. No serious side effects were detected with the treatment.</p></div><div><h3>Implications</h3><p>In this limited-sized case series, we found pronounced beneficial effects of low-dose IG in a large proportion of patients with infection-related ME/CFS. Further well-controlled studies are needed to verify the potential benefits of IG treatment in patients with ME/CFS with infection-driven symptomatology.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001310/pdfft?md5=1e2ad4ee43be610cd022fb34ec1e9f8f&pid=1-s2.0-S0149291824001310-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Analysis of Different Anesthesia and Analgesia Methods for Patients Undergoing Uniportal Video-assisted Lung Surgery","authors":"Xuan Gao MD ,&nbsp;Shuwei Wang MD ,&nbsp;Yi Li MD ,&nbsp;Di Zhou MD ,&nbsp;Xuemei Peng MM","doi":"10.1016/j.clinthera.2024.06.009","DOIUrl":"10.1016/j.clinthera.2024.06.009","url":null,"abstract":"<div><h3>Purpose</h3><p>The purpose of this study was to compare 3 intraoperative modalities to determine the best and most convenient one for pain control for uniportal lung surgery. This study compared general anesthesia<span> with serratus plane block, general anesthesia with epidural, and general anesthesia alone to examine postoperative pain scores in patients.</span></p></div><div><h3>Methods</h3><p>Eighty patients were enrolled and statistically analyzed. Three interventions were studied: general anesthesia with serratus plane block (group S), general anesthesia with thoracic epidural (group E), and general anesthesia only (group G). Outcome measures compared among the 3 groups included demographic characteristics; surgical types; anesthesia and operative time; postoperative pain scores; vital signs; morphine consumption at 0, 2, and 6 hours and day 1 and day 2 after surgery; incidence of opioid-related adverse events and chronic pain; hospital length of stay (LOS); and overall expenses. The numerical rating scale was used to assess the degree of pain on the first and second postoperative days. Postoperative morphine consumption, incidence of opioid-related side effects, hospital LOS, and overall hospital expenses were documented, as well as incidence of chronic postoperative pain.</p></div><div><h3>Findings</h3><p>There was no difference in the incidence of opioid-related adverse events and chronic pain, hospital LOS, and overall expenses among the 3 groups. After investigating factors that may influence hospital LOS and overall expenses, the multivariable analysis indicated that only longer operative time was associated with longer hospital stay and more hospital expenses.</p></div><div><h3>Implications</h3><p>This prospective study found that general anesthesia alone offers an easy and efficient approach resulting in similar postoperative pain scores and morphine consumption compared with nerve block and epidural. Longer operative time was associated with longer hospital stay and more hospital expenses. ClinicalTrials.gov identifier: NCT03839160. (<em>Clin Ther</em>. 2024;XX:XXX–XXX) © 2024 Elsevier HS Journals, Inc.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747612","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":"Current Approaches in Postapproval Vaccine Safety Studies Using Real-World Data: A Systematic Review of Published Literature","authors":"Juan (Joanne) Wu ScD, MS ,&nbsp;Manfred Hauben MD, MPH, MAS, DTM&H ,&nbsp;Muhammad Younus MBBS, MS, PhD","doi":"10.1016/j.clinthera.2024.06.005","DOIUrl":"10.1016/j.clinthera.2024.06.005","url":null,"abstract":"<div><p>Purpose: Well-designed observational postmarketing studies using real-world data (RWD) are critical in supporting an evidence base and bolstering public confidence in vaccine safety. This systematic review presents current research methodologies in vaccine safety research in postapproval settings, technological advancements contributing to research resources and capabilities, and their major strengths and limitations.</p><p>Methods: A comprehensive search was conducted using PubMed to identify relevant articles published from January 1, 2019, to December 31, 2022. Eligible studies were summarized overall by study design and other study characteristics (eg, country, vaccine studied, types of data source, and study population). An in-depth review of select studies representative of conventional or new designs, analytical approaches, or data collection methods was conducted to summarize current methods in vaccine safety research.</p><p>Findings: Out of 977 articles screened for inclusion, 135 were reviewed. The review shows that recent advancements in scientific methods, digital technology, and analytic approaches have significantly contributed to postapproval vaccine safety studies using RWD. “Near real-time surveillance” using large datasets (via collaborative or distributed databases) has been used to facilitate rapid signal detection that complements passive surveillance. There was increasing appreciation for self-controlled case-only designs (self-controlled case series and self-controlled risk interval) to assess acute-onset safety outcomes, artificial intelligence, and natural language processing to improve outcome accuracy and study timeliness and emerging artificial intelligence–based analysis to capture adverse events from social media platforms.</p><p>Implications: Continued development in the area of vaccine safety research methodologies using RWD is warranted. The future of successful vaccine safety research, especially evaluation of rare safety events, is likely to comprise digital technologies including linking RWD networks, machine learning, and advanced analytic methods to generate rapid and robust real-world safety information.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981898","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":"Direct Oral Anticoagulants and Concomitant Anti-seizure Medications: A Retrospective, Case–Control Study in a Real-World Setting","authors":"","doi":"10.1016/j.clinthera.2024.06.002","DOIUrl":"10.1016/j.clinthera.2024.06.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case–control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM </span>monotherapy, in age- and gender-matched controls.</p></div><div><h3>Methods</h3><p>Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid<span> (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province.</span></p></div><div><h3>Findings</h3><p>Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group.</p></div><div><h3>Implications</h3><p>Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554364","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":"A Retrospective Case Series Analysis of Pregnancy and COVID-19 Based on a Global Postmarketing COVID-19 Surveillance Program","authors":"Elena Beyzarov PharmD,&nbsp;Yan Chen MD, PhD,&nbsp;Patrick Caubel MD, PhD","doi":"10.1016/j.clinthera.2024.06.012","DOIUrl":"10.1016/j.clinthera.2024.06.012","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;To document and characterize COVID-19 cases involving pregnancy in the context of exposure to pharmaceutical products.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This retrospective case series analysis leveraged the Pfizer safety database containing worldwide adverse event data related to use of Pfizer products between October 1, 2019 and November 3, 2022. Selected Medical Dictionary for Drug Regulatory Activities (Version 25.0) Preferred Terms and subsequent clinical review were used to identify COVID-19 cases involving female patients who received Pfizer products during pregnancy and infants with intrauterine exposure to Pfizer products.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;As of November 3, 2022, 504 pregnancy cases (426 maternal; 78 infants) were identified. Most maternal cases reported COVID-19 during the third trimester, and (when known) 52% of cases involved presentation or progression of severe COVID-19 with associated complications requiring hospitalization, and often intensive management (eg, mechanical ventilation, oxygen support) and emergent delivery. Twenty-three maternal cases were fatal; patients developed severe COVID-19 disease involving multisystem deterioration (eg, cardiopulmonary injury/decompensation, coagulopathies, septic/hemorrhagic shock) and frequently required risk-benefit decisions regarding maintaining/prolonging pregnancies to improve fetal viability while attempting to improve or stabilize maternal conditions or electing to either terminate pregnancies or induce emergent deliveries. Approximately 40% of maternal cases reported medical history involving at least one underlying condition (eg, diabetes, respiratory disorders, renal/hepatic disease, cardiac disease, obesity, autoimmune conditions) considered potentially associated with susceptibility to infection/adverse outcome of infection, or twin/triplet pregnancy, which may further complicate COVID-19 disease. Most cases with known fetal outcomes reported normal newborns including preterm/low birth weight infants, which occurred in many cases involving emergent preterm delivery due to deteriorating maternal conditions. The remaining smaller proportion of cases involved abnormal newborn/perinatal/postperinatal complications (eg, premature births, respiratory distress, alveolar damage, meconium aspiration with hypoxic-ischemic encephalopathy), intrauterine/neonatal death (due to multiple concurrent complications such as neonatal sepsis, hypoxemia/acute respiratory distress, potential cardiac damage, mucormycosis) and congenital anomaly (eg, intrauterine growth restriction in association with contracting COVID-19). Among infants tested within our dataset, 28 cases involved reference to infants who tested positive for COVID-19 infection at birth or shortly thereafter, with vertical transmission suspected only in 2 infants.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implication&lt;/h3&gt;&lt;p&gt;This large retrospective case series provides additional perspectives regarding potential impact o","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001504/pdfft?md5=e91603b22a8846643195714d81e0ab89&pid=1-s2.0-S0149291824001504-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Safety of a 1:1 Mixture of Doxecitine and Doxribtimine: Open-label Phase 1 Single Ascending Dose and Food Effect Studies in Healthy Adults","authors":"Aravind Mittur PhD ,&nbsp;Susan A. VanMeter MD ,&nbsp;Elmar Orujov MD ,&nbsp;Paul Glidden PhD","doi":"10.1016/j.clinthera.2024.06.006","DOIUrl":"10.1016/j.clinthera.2024.06.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;Doxecitine (deoxycytidine [dC]) and doxribtimine (deoxythymidine [dT]) powder for oral solution is a 1:1 mixture consisting of equal weights 2’-deoxycytidine (dC) and 2’-deoxythymidine (dT). Doxecitine and doxribtimine (referred to as study drug) is being developed as treatment for people with thymidine kinase 2 deficiency (TK2d). TK2d is an ultra-rare mitochondrial DNA depletion and multiple deletion syndrome characterized by progressive muscle weakness and premature death. Here, we report the pharmacokinetics (PK), the effect of food, and the tolerability of 2 study drug formulations, evaluated in 2 studies (Study MT-1621-103 and Study MT-1621-105).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;A sequential, ascending 1:1 dose ratio was used for both studies (n = 14 healthy volunteer adult participants/study). After a 28-day (Study MT-1621-103) or 35-day (Study MT-1621-105) screening period, participants fasted overnight and sequentially received 86.6, 173.4, and 266.6 mg/kg study drug with a 48-hour PK assessment period and 48-hour washout period between doses. After 48 additional hours, participants were fed a high-fat meal and received 266.6 mg/kg study drug. Plasma and urine were collected before dosing and throughout the 48-hour PK period. dC and dT concentrations were analyzed by validated liquid chromatography mass spectrometry methods. Safety was evaluated throughout the study and at 2-week follow-up.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;Plasma levels of dC and dT increased rapidly and dose-dependently above endogenous levels for both formulations, with a median T&lt;sub&gt;max&lt;/sub&gt; of 1 to 2 hours under fasting conditions. Post-dose plasma dC and dT concentrations declined to nearly pre-dose (baseline) concentrations after 8 to 12 hours, suggesting rapid elimination. Peak and extent of plasma exposure (baseline-corrected C&lt;sub&gt;max&lt;/sub&gt; and AUC&lt;sub&gt;0-t&lt;/sub&gt;) tended to increase less than dose-proportionally for plasma dC and greater than dose-proportionally for plasma dT. PK variability of dC and dT was moderate-to-high (&gt;30%). Administration with food delayed T&lt;sub&gt;max&lt;/sub&gt; to a median of 2 to 4 hours and increased plasma exposure: baseline-corrected plasma dC C&lt;sub&gt;max&lt;/sub&gt; and AUC&lt;sub&gt;0-t&lt;/sub&gt; increased by ∼79% to 96% and 137% to 250%, respectively, and dT C&lt;sub&gt;max&lt;/sub&gt; and AUC&lt;sub&gt;0-t&lt;/sub&gt; increased by 27% to 29% and 74% to 89%, respectively, indicating a significant food effect. Renal clearance played a minor role in the elimination of systemically available intact dC and dT (F&lt;sub&gt;e&lt;/sub&gt;&lt;0.3%). The study drug was generally well tolerated; most frequent study-drug–related adverse events (AEs) were diarrhea (n = 4/29, 14%) and dizziness (n = 3/29, 10%). Most AEs were mild-to-moderate in severity.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;p&gt;Doxecitine and doxribtimine are orally bioavailable in the intended clinical dose range. The PK profile supports a formulation consisting of equal doses of doxecitine and doxribtimine, ","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001437/pdfft?md5=4d097fd73bc888c0c9d73559941b281b&pid=1-s2.0-S0149291824001437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge Graphs in Pharmacovigilance: A Scoping Review","authors":"","doi":"10.1016/j.clinthera.2024.06.003","DOIUrl":"10.1016/j.clinthera.2024.06.003","url":null,"abstract":"<div><h3>Purpose</h3><p>To critically assess the role and added value of knowledge graphs in pharmacovigilance, focusing on their ability to predict adverse drug reactions.</p></div><div><h3>Methods</h3><p>A systematic scoping review was conducted in which detailed information, including objectives, technology, data sources, methodology, and performance metrics, were extracted from a set of peer-reviewed publications reporting the use of knowledge graphs to support pharmacovigilance signal detection.</p></div><div><h3>Findings</h3><p>The review, which included 47 peer-reviewed articles, found knowledge graphs were utilized for detecting/predicting single-drug adverse reactions and drug-drug interactions, with variable reported performance and sparse comparisons to legacy methods.</p></div><div><h3>Implications</h3><p>Research to date suggests that knowledge graphs have the potential to augment predictive signal detection in pharmacovigilance, but further research using more reliable reference sets of adverse drug reactions and comparison with legacy pharmacovigilance methods are needed to more clearly define best practices and to establish their place in holistic pharmacovigilance systems.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001449/pdfft?md5=f9f33cb64cea55fc0e6c0a5062b887ee&pid=1-s2.0-S0149291824001449-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Anti-Inflammatory Diet and Fecal Microbiota Transplant in Psoriatic Arthritis","authors":"","doi":"10.1016/j.clinthera.2024.05.005","DOIUrl":"10.1016/j.clinthera.2024.05.005","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span><span>Psoriatic arthritis (PsA) is a chronic inflammatory condition with complex and heterogenous manifestations. Although a myriad of treatment options including biologic medications are available to alleviate symptoms and slow </span>disease progression, there is currently no cure for this condition. There has been a recent emergence of understanding about the relationship between the </span>gut microbiome<span> and immune-mediated inflammatory diseases. This has generated interest in the potential role of dietary interventions, particularly anti-inflammatory diets, and </span></span>fecal microbiota transplant (FMT) as novel therapeutic approaches. The purpose of this narrative review is to examine the role of an anti-inflammatory diet and FMT in turn and whether their combination may offer alternate approaches for the management of PsA.</p></div><div><h3>Methods</h3><p>Our non-systematic narrative review was informed by a literature search using PubMed and Google Scholar using the terms anti-inflammatory diet, FMT, nutrition supplements<span>, and PsA. Preclinical studies and non-English language articles were excluded when synthesizing the narrative review.</span></p></div><div><h3>Findings</h3><p>Current randomized controlled trials<span><span> (RCTs) and observational evidence suggest that a hypocaloric diet<span> or Mediterranean diet can help achieve weight loss among PsA patients who are overweight or obese, which in turn reduces inflammation and improves disease activity. However, there is no strong data to support the beneficial effects of </span></span>intermittent fasting<span>, vitamin supplements, turmeric supplements, probiotics, or omega-3 fatty acid supplements in PsA. Current evidence on the use of FMT in PsA is limited as only one small RCT has been conducted which did not demonstrate efficacy for improving clinical symptoms.</span></span></p></div><div><h3>Implications</h3><p>Clinicians can consider recommending hypocaloric or Mediterranean diets as an adjunct to standard management of PsA, possibly under the guidance of a dietician. Further research is needed to explore the beneficial effects of the synergistic role of combining an anti-inflammatory diet with FMT in PsA.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305608","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":"Tacrolimus Related Acute Pancreatitis: An Observational, Retrospective, Pharmacovigilance Study","authors":"","doi":"10.1016/j.clinthera.2024.04.005","DOIUrl":"10.1016/j.clinthera.2024.04.005","url":null,"abstract":"<div><h3>Purpose</h3><p>Recent case reports have drawn attention to the emergence of acute pancreatitis, a potentially life-threatening complication associated with tacrolimus. This study uses the Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate the risk signal of acute pancreatitis associated with calcineurin inhibitors (CNIs), with a focus on tacrolimus.</p></div><div><h3>Methods</h3><p>We conducted an observational retrospective pharmacovigilance study utilizing the FAERS database, encompassing data from its inception to the third quarter of 2023. The assessment of the association between CNIs and acute pancreatitis was carried out using the Information Component (IC) and Reporting Odds Ratio (ROR). Logistic regression analysis was employed to elucidate factors contributing to fatal outcomes. All analyses were performed using R version 3.2.5.</p></div><div><h3>Finding</h3><p>We identified 221 cases of acute pancreatitis linked to CNIs. The median age of individuals experiencing acute pancreatitis induced by tacrolimus was 43, with a predominant occurrence among male patients. Our study showed a significant association between CNIs and acute pancreatitis (ROR 1.82 [1.60–2.08], IC 0.85 [3.66–3.92]). Comparing tacrolimus and cyclosporine, the signal for tacrolimus seemed to be higher. Further analysis revealed that, with the exception of patients aged 60 and above, the signal for tacrolimus remained stable. Contrastingly, the signal for cyclosporine was unstable and limited to the male group and individuals aged less than 20 years. In cases of CNIs-related acute pancreatitis, the mortality rate was 31.67% (70/221 cases). Logistic regression analysis indicated that a younger age acts as a protective factor for death due to CNIs-related acute pancreatitis (OR 0.943, 95% CI 0.915–0.972, <em>P</em> = 0.000).</p></div><div><h3>Implications</h3><p>Our study has identified a safety signal for tacrolimus in relation to acute pancreatitis. Additionally, we observed advanced age as a significant risk factor for tacrolimus-related acute pancreatitis, leading to mortality. Given the widespread use of tacrolimus, it is crucial for healthcare providers to be vigilant and informed about the potential association with acute pancreatitis.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824000833/pdfft?md5=247d0b530589785246ff94cf2560443e&pid=1-s2.0-S0149291824000833-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Givinostat Oral Suspension","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.06.008","DOIUrl":"10.1016/j.clinthera.2024.06.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603398","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}