Christine Eisenhower, Evan Cano, Madison Smith, Ryan Virgin, Margaret M Charpentier
{"title":"Bolus Dosing of Alteplase in Hemodynamically Unstable Acute Pulmonary Embolism.","authors":"Christine Eisenhower, Evan Cano, Madison Smith, Ryan Virgin, Margaret M Charpentier","doi":"10.1177/10600280241288601","DOIUrl":"10.1177/10600280241288601","url":null,"abstract":"","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"585-586"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602566","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}
Aliya Abdulla, Kevin R Donahue, Courtney Hall, Lauren G Culver, Celia Morton
{"title":"Incidence of Venous Thromboembolism Post-Oral Anticoagulation Reversal in Intracranial Hemorrhage Patients.","authors":"Aliya Abdulla, Kevin R Donahue, Courtney Hall, Lauren G Culver, Celia Morton","doi":"10.1177/10600280241297701","DOIUrl":"10.1177/10600280241297701","url":null,"abstract":"<p><strong>Background: </strong>Rates of in-hospital venous thromboembolism (VTE) in the intracranial hemorrhage (ICH) population post oral anticoagulation (AC) reversal are as high as 10%. Guidelines recommend the initiation of prophylactic AC 24 to 48 hours post ICH; however, there is no guidance regarding optimal VTE prophylaxis post-reversal.</p><p><strong>Objective: </strong>This study aimed to identify the incidence of thromboembolism post oral AC reversal in patients presenting with ICH and describe VTE prophylaxis timing and agent selection.</p><p><strong>Methods: </strong>This was a retrospective, descriptive study conducted within a single health system. Patients on AC who received reversal agents 4-factor prothrombin complex concentrate (4F-PCC) with or without vitamin K, andexanet alfa, and/or idarucizumab for AC-associated ICH were included. The primary endpoint was incidence of in-hospital VTE post-reversal. Secondary endpoints included AC utilization specifications, length of stay, and in-hospital mortality.</p><p><strong>Results: </strong>There were 118 patients (57%) who received 4F-PCC and 89 patients (43%) who received andexanet alfa for reversal post-ICH. Overall, 195 patients (94.2%) achieved hemostasis. Eight patients had incidence of VTE (3.9%), and of those, 6 patients (75%) were reinitiated on AC, all of which utilized prophylactic heparin. The median time from reversal to VTE was 55.9 days (interquartile range [IQR] = 21.2-72.4). For all patients on AC, the median time to initiation from reversal was 3.98 days (IQR = 2.5-6.01), and for those with incidence of thrombosis, the median time to AC initiation was 6.4 days (IQR = 2.6-13.1). Mortality occurred in 13 patients (6.3%).</p><p><strong>Conclusion and relevance: </strong>This patient population is complex in that the need to achieve hemostasis with AC reversal must be balanced with the risk of VTE. Further studies are needed to determine the ideal timing and agent selection for VTE prophylaxis initiation post ICH reversal.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"501-510"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674946","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}
Ashley E Woodruff, Olivia Haight, Michelle Maj, Kevin Mills, Maya R Chilbert
{"title":"Readmission Rates in Reduced Ejection Fraction Heart Failure Patients on Triple Guideline-Directed Medical Therapy at Hospital Discharge.","authors":"Ashley E Woodruff, Olivia Haight, Michelle Maj, Kevin Mills, Maya R Chilbert","doi":"10.1177/10600280251336751","DOIUrl":"https://doi.org/10.1177/10600280251336751","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) places a significant burden on the health care system, driven primarily by HF hospitalizations. While HF guidelines recommend initiation of quadruple guideline-directed medical therapy (GDMT) in patients with HF with reduced ejection fraction (HFrEF), in-hospital initiation of quadruple therapy remains a clinical challenge, particularly in patients with additional high-risk comorbidities.</p><p><strong>Objective: </strong>The purpose of this study was to compare the efficacy and safety of triple GDMT with a sodium-glucose cotransporter inhibitor (SGLTi) vs mineralocorticoid receptor antagonist (MRA) added to beta blocker and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNi).</p><p><strong>Methods: </strong>This retrospective cohort study was conducted in hospitalized patients with acute HFrEF. Patients who received triple GDMT therapy with a SGLTi or MRA added to beta blocker and ACEi/ARB/ARNi therapy at discharge were compared. The primary outcome was 90-day readmission for HF with secondary outcomes of 30-day readmission for HF and 90-day readmission for GDMT-associated adverse events.</p><p><strong>Results: </strong>A total of 210 patients were included (SGLTi group, n = 105; MRA group, n = 105). Rates of 90-day readmission for HF between SGLTi and MRA groups were 23 (21.90%) vs 15 (14.29%); <i>P</i> = 0.1516. After adjusting for co-variables associated with 90-day readmission, 90-day readmission for HF was not significantly different in patients in the SGLTi vs MRA group (adjusted hazard ratio = 1.742, 95% confidence interval [CI] = 0.833 to 3.434; <i>P</i> = 0.1092). Rates of 90-day readmission for GDMT-associated adverse events were similar between groups.</p><p><strong>Conclusion and relevance: </strong>In this cohort of patients receiving triple GDMT at discharge after hospitalization for acute HFrEF, triple therapy with an SGLTi vs MRA resulted in similar rates of 90-day HF hospitalization.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251336751"},"PeriodicalIF":2.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191384","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}
Taylor M Law, Spencer L Roper, Amanda McKinney, Cassey Starnes, Joshua Rains, Ji-Ming Yune, Nathan Hieb, Reagan Bollig, Brian Daley, A Shaun Rowe
{"title":"Evaluation of Symptom-Triggered Benzodiazepines Versus Phenobarbital for Alcohol Withdrawal Syndrome in Trauma-Surgical Intensive Care Patients.","authors":"Taylor M Law, Spencer L Roper, Amanda McKinney, Cassey Starnes, Joshua Rains, Ji-Ming Yune, Nathan Hieb, Reagan Bollig, Brian Daley, A Shaun Rowe","doi":"10.1177/10600280251340164","DOIUrl":"https://doi.org/10.1177/10600280251340164","url":null,"abstract":"<p><strong>Background: </strong>The standard of care for alcohol withdrawal syndrome (AWS) is symptom-triggered benzodiazepines. There is an interest in utilizing phenobarbital first line for AWS in trauma-surgical patients.</p><p><strong>Objective: </strong>The objective of this study was to compare a preemptive phenobarbital monotherapy protocol to symptom-triggered benzodiazepines for the prevention or treatment of AWS in the trauma-surgical patients.</p><p><strong>Methods: </strong>This was a single-center, retrospective study to evaluate the AWS standard of care for the Trauma Surgical Critical Care Service. Patients were divided into groups based on AWS protocol. The primary outcome was intensive care unit (ICU) length of stay (LOS). Secondary outcomes included: hospital mortality, hospital LOS, use of adjunctive agents for sedation, and incidence of mechanical ventilation rates.</p><p><strong>Results: </strong>A total of 514 patients were screened for eligibility, and 200 patients met inclusion criteria, with 100 patients being in each group. Patients who received the symptom-triggered benzodiazepine protocol had similar ICU LOS (median [IQR], 2.6 days [1.4-5.6 days] vs 2.9 days [1.8-4.7 days]; <i>P</i> = 0.4) and hospital LOS (8.1 days [3.9-16.9 days] vs 7.1 days [3.9-11.2 days]; <i>P</i> = 0.05) compared with the phenobarbital protocol. Hospital mortality was significantly lower in those who received phenobarbital (4% vs 14%; <i>P</i> = 0.02), as was use of adjunctive sedative agents (22% vs 46%; <i>P</i> < 0.001), and mechanical ventilation rates (9% vs 31%; <i>P</i> < 0.001) when compared with symptom-triggered benzodiazepines.</p><p><strong>Conclusion and relevance: </strong>Trauma-surgical patients receiving phenobarbital for prevention or treatment of AWS had similar ICU and hospital LOS compared with symptom-triggered benzodiazepines. The use of a phenobarbital protocol was associated with lower mortality, mechanical ventilation, and adjunctive sedative medication use.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251340164"},"PeriodicalIF":2.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172474","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}
Emilie J Lynch, Sarah Jane E Faro, Alec M Lindstrom, Nadia A Sethi, Wendy Y Wang, Nathan D Seligson
{"title":"Revumenib for Relapsed or Refractory Acute Leukemia With a <i>KMT2A</i> Translocation.","authors":"Emilie J Lynch, Sarah Jane E Faro, Alec M Lindstrom, Nadia A Sethi, Wendy Y Wang, Nathan D Seligson","doi":"10.1177/10600280251341279","DOIUrl":"https://doi.org/10.1177/10600280251341279","url":null,"abstract":"<p><strong>Objective: </strong>To review the pharmacology, efficacy, and safety of revumenib (Revuforj) for relapsed or refractory (r/r) acute leukemia with a lysine methyltransferase 2A (<i>KMT2A)</i> gene rearrangement or translocation (<i>KMT2Ar</i>).</p><p><strong>Data sources: </strong>A literature search was conducted using PubMed/MEDLINE, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and April 23, 2025. Keywords included Revuforj, revumenib, SNDX-5613, <i>KMT2A</i>, <i>MLL1</i>, and menin.</p><p><strong>Study selection and data extraction: </strong>All English-language studies involving revumenib for r/r acute leukemia with a <i>KMT2Ar</i> were included.</p><p><strong>Data synthesis: </strong>Revumenib, a protein-protein inhibitor that interrupts the interaction between the <i>KMT2A</i> protein and the scaffold protein menin, was granted approval by the Food and Drug Administration (FDA) for r/r acute leukemia with <i>KMT2Ar</i> based on a phase 2 clinical trial in adult and pediatric patients (n = 57), which reported a complete remission or complete remission with partial hematologic recovery of 22.8%. Common grade 3/4 adverse reactions reported for revumenib include infectious (febrile neutropenia 33%; infection 29%; bacterial infection 20%) and hematologic events (differentiation syndrome 13%; hemorrhage 9%; thrombosis 5%). Grade 3/4 QT prolongation, the primary dose-limiting adverse effect, was present in 12% of patients. Differentiation syndrome, related to revumenib's antileukemic effect, was observed in 29% of patients (grade 3/4: 13%; grade 5: <1%). We also include long-term follow-up for a total of 104 and 135 patients for efficacy and safety results, respectively.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:In the high-risk disease of r/r acute leukemia with <i>KMT2Ar</i>, given limited treatment options, revumenib appears to be a viable, novel treatment option demonstrating clinical efficacy and a manageable adverse effect profile that can be utilized as a bridge to stem cell transplant. Existing therapy options in this setting may include additional traditional chemotherapy, chimeric antigen receptor T-cell therapy (CAR-T), antibody-drug conjugates (eg, gemtuzumab, inotuzumab), bispecific T-cell engager (BiTE) therapies (eg, blinatumomab), DNA methyltransferase inhibitors (eg, azacitidine, decitabine), histone deacetylase inhibitors (eg, vorinostat, panobinostat), and BCL-2 inhibitors (venetoclax).</p><p><strong>Conclusions: </strong>Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with <i>KMT2Ar</i>.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251341279"},"PeriodicalIF":2.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172477","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}
Mei Wang, J Michael Paterson, Francis Nguyen, Deborah M Siegal, Laura Targownik, Anne M Holbrook
{"title":"Association of Direct Oral Anticoagulant-Proton Pump Inhibitor Co-Therapy with Adverse Outcomes: A Population-Based Cohort Study.","authors":"Mei Wang, J Michael Paterson, Francis Nguyen, Deborah M Siegal, Laura Targownik, Anne M Holbrook","doi":"10.1177/10600280251337209","DOIUrl":"https://doi.org/10.1177/10600280251337209","url":null,"abstract":"<p><strong>Background: </strong>Direct-acting oral anticoagulants (DOACs) are first-line therapy for atrial fibrillation and for venous thromboembolism prevention and treatment. In addition, proton pump inhibitors (PPIs) are recommended by the ACC Expert Consensus for patients receiving DOAC.</p><p><strong>Objective: </strong>To determine the risk of clinically important thromboembolic and bleeding events and death in patients concomitantly prescribed DOACs and PPIs compared with DOAC alone.</p><p><strong>Methods: </strong>We undertook a population-based cohort study of Ontario residents aged 66 years or older who were newly dispensed a DOAC from 2009 to 2020. The primary outcome was a composite of clinically relevant bleeding, thrombotic events, and all-cause death. We then used a time-dependent Cox regression model to estimate the adjusted hazard of outcomes during time periods where patients were exposed vs not exposed to PPI.</p><p><strong>Results: </strong>We included 283 771 new DOAC users (mean age 78.3 years, 49.4% female). The age/sex-standardized outcome event rate of the composite outcome was higher in the DOAC-PPI cohort [20.2 (95% CI 20.0-20.5) per 100 person-years] than in the DOAC-alone cohort [15.2 (95% CI 15.1-15.4) per 100 person-years]. In time-dependent Cox regression analyses examining time periods during DOAC-PPI co-therapy vs DOAC alone, risks were elevated for all outcomes during periods of PPI co-therapy, suggesting residual confounding. In a secondary analysis of patients receiving DOAC-PPI co-therapy (n = 115 493), periods of DOAC-PPI co-therapy were associated with a greater hazard for death (HR 2.24, 95% CI 2.14-2.35), but a lower risk for both thrombosis (HR 0.93, 95% CI 0.89-0.96) and clinically relevant bleeding (HR 0.79, 95% CI 0.76-0.81).</p><p><strong>Conclusion and relevance: </strong>Our cohort study of older adults suggests that DOAC-PPI co-therapy is associated with decreased upper GI bleeding but increased mortality. Since the implications are major and may be due to residual confounding, we recommend that the findings be verified in randomized trials before clinical application.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251337209"},"PeriodicalIF":2.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172472","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":"Zolbetuximab-clzb: Targeting Claudin 18.2 in Advanced Gastric and Gastroesophageal Adenocarcinoma.","authors":"Gabrielle L Gorwitz, David L DeRemer","doi":"10.1177/10600280251342801","DOIUrl":"https://doi.org/10.1177/10600280251342801","url":null,"abstract":"<p><strong>Objective: </strong>To review the pharmacology, efficacy, and safety of zolbetuximab for the treatment of adults with HER2 negative gastric (GC) or gastroesophageal junction (GEJ) adenocarcinomas whose tumors are claudin 18.2 (CLDN18.2)-positive.</p><p><strong>Data sources: </strong>A literature search was conducted using PubMed and MEDLINE databases, published abstracts, and studies from ClinicalTrials.gov between 2003 and February 2024. Keywords included zolbetuximab, IMAB362, claudiximab, claudin 18.2, gastric, and gastroesophageal junction cancer.</p><p><strong>Data extraction: </strong>All applicable publications, package inserts, meeting abstracts, and clinical trials with zolbetuximab were reviewed.</p><p><strong>Data synthesis: </strong>Zolbetuximab is a novel chimeric monoclonal antibody which targets the tight junction protein CLDN18.2. In 2 phase III clinical trials (SPOTLIGHT, GLOW), zolbetuximab when combined with a fluoropyrimidine-containing regimen, significantly improved progression free survival and overall survival in a frontline setting in HER2 negative patients with GC/GEJ adenocarcinomas that express CLDN18.2. The most common adverse reactions of any grade in patients receiving zolbetuximab with chemotherapy were nausea, vomiting, fatigue, decreased appetite, and diarrhea.Relevant to patient care and clinical practice in comparison with existing drugs:Assessment of PD-L1 and CLDN18.2 will assist clinicians in therapeutic decision selection with immune checkpoint inhibitors and zolbetuximab addition to chemotherapy in a frontline setting.</p><p><strong>Conclusion: </strong>The addition of zolbetuximab to a fluoropyrimidine based chemotherapy regimen in highly expressed CLDN18.2 GC/GEJ tumors is associated with improved survival.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251342801"},"PeriodicalIF":2.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155697","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}
Jessica Briscoe, Lauren Caldwell, Aaron Cohen, Jeremy Greenberg, Jessica Parker, Alicia Stowe, Megan Van Berkel Patel
{"title":"Comparative Efficacy and Safety of Basal/Correctional Vs Basal/Bolus/Correctional Insulin Regimens in Medical Intensive Care Unit Patients Receiving Continuous Enteral Nutrition.","authors":"Jessica Briscoe, Lauren Caldwell, Aaron Cohen, Jeremy Greenberg, Jessica Parker, Alicia Stowe, Megan Van Berkel Patel","doi":"10.1177/10600280251340180","DOIUrl":"https://doi.org/10.1177/10600280251340180","url":null,"abstract":"<p><strong>Background: </strong>While glycemic control is essential in critically ill patients, the optimal insulin regimen for patients receiving continuous enteral nutrition (CEN) is unknown.</p><p><strong>Objective: </strong>This study compares glycemic control in basal/correctional vs basal/bolus/correctional insulin regimens in intensive care unit (ICU) patients receiving CEN.</p><p><strong>Methods: </strong>This retrospective study included patients ≥18 years old, admitted to the medical critical care service with administration of CEN and ≥20 units of insulin detemir daily for ≥48 hours. Patients receiving non-insulin hypoglycemic agents were excluded. The primary outcome was the comparison of glycemic control, assessed by mean blood glucose and percent of glucose checks in target range. Secondary outcomes included the comparison of hypoglycemia, hyperglycemic emergencies, and glycemic variability between groups.</p><p><strong>Results: </strong>A total of 100 patients were included, with 50 patients per group. Mean blood glucose and percent of blood glucose checks in the target range were similar between basal/correctional and basal/bolus/correctional groups (204.2 vs 194.2 mg/dL, <i>P</i> = 0.2433 and 37.8% vs 43.1%, <i>P</i> = 0.3182, respectively). There were no differences in hypoglycemia or hyperglycemic emergencies. Among patients receiving ≥60 units of insulin daily, the basal/bolus/correctional regimen was associated with lower mean blood glucose (197.1 vs 248.5 mg/dL, <i>P</i> < 0.0001) and increased glucose checks in target range (43.5% vs 9.1%, <i>P</i> = 0.0040) without increased hypoglycemia.</p><p><strong>Conclusion and relevance: </strong>Among ICU patients requiring ≥20 units of insulin detemir daily while receiving CEN, basal/correctional and basal/bolus/correctional insulin regimens appear to offer similar glycemic control, but basal/bolus/correctional regimens may improve glycemic control in patients requiring ≥60 units of insulin daily.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251340180"},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141228","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}
Chris Destache, Kelsey Witherspoon, Corey Yeates, David Quimby, Faran Ahmad, Renuga Vivekanandan
{"title":"Evaluating Cefepime Dosing Strategies in <i>Pseudomonas aeruginosa</i> Bacteremia: A Retrospective Cohort Analysis.","authors":"Chris Destache, Kelsey Witherspoon, Corey Yeates, David Quimby, Faran Ahmad, Renuga Vivekanandan","doi":"10.1177/10600280251339770","DOIUrl":"https://doi.org/10.1177/10600280251339770","url":null,"abstract":"<p><strong>Background: </strong><i>Pseudomonas aeruginosa</i> (PA) bacteremia is associated with poor clinical outcomes.</p><p><strong>Objective: </strong>The purpose of this study was to evaluate treatment effect and patient outcomes from different antimicrobials for PA bacteremia from 2020 to 2022.</p><p><strong>Methods: </strong>This was a retrospective review of 2020 to 2022 hospitalized patients with PA bacteremia at our institution. Patients from January 2020 to July 2022 with culture-positive PA were identified. Data collected included demographics, hospitalization and drug treatment length, vasopressor use or mechanical ventilation, and admission acute and physiologic health evaluation II score (APACHE II) score and hospital mortality. Directed therapy for PA, including dose, interval, and minimal inhibitory concentration (MIC) data, was evaluated. Data were analyzed by SPSS. Data are presented as mean ± SD or percentage. A priori significance was <i>P</i> ≤ 0.05.</p><p><strong>Results: </strong>A total of 111 PA bacteremias occurred from 2020 to 2022; 65% of patients were male. Mean (± SD) age was 71 ± 13 years, and weight was 89.7 ± 23 kg. Mean hospitalization length and duration of antibiotics were 12 ± 13 days and 7.1 ± 5.9 days, respectively. The PA bacteremia was treated with piperacillin-tazobactam (45%) or cefepime (43%). Thirty- seven (33%) PA-infected patients expired. Significantly more 8 of 18 (44%) cefepime patients died when receiving 4 g/d (1 g q 6 h) compared with 1 (9%) of 11 receiving 6 g/d (2 g q 8 h) (<i>P</i> < 0.05). The APACHE II score was significantly higher for expired patients (survival 13.9 ± 5.7; expired 22 ± 8.3 group, <i>P</i> < 0.001).</p><p><strong>Conclusions and relevance: </strong>The APACHE II score was significantly higher for PA bacteremic patients who expired. Treatment of the bacteremia with cefepime 4 g/d resulted in significant mortality compared to 6 g/d.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251339770"},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141230","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}
Alejandro Martínez Pradeda, Pablo Feijoo Vilanova, Elena Fernández Gabriel, Víctor Giménez Arufe, Ana María Vale López, Jorge Suanzes-Hernández, Luis Margusino-Framiñán, Víctor Noriega Concepción
{"title":"Real-World Safety Profile of Ibrutinib in Chronic Lymphocytic Leukemia: A Focus on Adverse Events, Discontinuations, and Effectiveness Outcomes.","authors":"Alejandro Martínez Pradeda, Pablo Feijoo Vilanova, Elena Fernández Gabriel, Víctor Giménez Arufe, Ana María Vale López, Jorge Suanzes-Hernández, Luis Margusino-Framiñán, Víctor Noriega Concepción","doi":"10.1177/10600280251334133","DOIUrl":"https://doi.org/10.1177/10600280251334133","url":null,"abstract":"<p><strong>Background: </strong>Ibrutinib has transformed chronic lymphocytic leukemia (CLL) treatment, offering significant survival benefits in clinical trials. However, real-world evidence is essential to understand its safety and efficacy in broader patient populations.</p><p><strong>Objective: </strong>To evaluate ibrutinib safety and effectiveness in a real-world cohort of CLL patients focusing on dose reductions, adverse events, and survival outcomes.</p><p><strong>Methods: </strong>This single-center, retrospective, observational study of CLL patients treated with ibrutinib was conducted between January 2015 and June 2023. Data were retrieved from the IANUS electronic medical records including patient demographics, treatment indications, genetic markers, comorbidities, adverse events, and dose changes.</p><p><strong>Results: </strong>This study involved 90 patients with a median age of 71.5 years. Most patients presented with advanced-stage disease (BINET C: 46%, RAI IV: 25%). Cardiovascular comorbidities were common (70%) and 11% had prior bleeding events. Severe adverse events (grade 3-4) occurred in most patients (60%) with infections (33.3%) and neutropenia (14.4%) being the most common. Dose reductions were required in 11.1% of patients mainly due to hematological toxicities and 22% discontinued treatment due to adverse events. However, dose reductions and severe adverse events did not significantly affect overall survival or progression-free survival. The overall response rate was 82.2%, with 42.2% achieving complete remission. Multivariate analysis identified age and comorbidities as significant predictors of severe adverse events but not survival outcomes.</p><p><strong>Conclusion and relevance: </strong>Ibrutinib remains an effective treatment for lymphocytic leukemia, even in patients with comorbidities and high-risk genetic characteristics. The study supports dose adjustment as a viable strategy for managing toxicities without compromising efficacy. These findings highlight the need for personalized care and proactive management of adverse events in clinical practice, particularly in elderly patients or those with multiple comorbidities. Long-term clinical studies are essential to refine treatment strategies and improve patient outcomes.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280251334133"},"PeriodicalIF":2.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141236","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}