Clinical therapeutics最新文献

{"title":"Vancomycin Dosing in Patients on Intermittent Hemodialysis—A Retrospective Study","authors":"Jacqueline Martin MClinPharm ,&nbsp;Colin M. Curtain PhD ,&nbsp;Mohammed S. Salahudeen PhD ,&nbsp;Sonja Janson MBBS ,&nbsp;Sachin Kodgire DM (Nephrology) ,&nbsp;Danny Tsai PhD","doi":"10.1016/j.clinthera.2025.01.001","DOIUrl":"10.1016/j.clinthera.2025.01.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To determine the incidence of therapeutic target attainment using a three-times per week protocol for vancomycin therapy given during the last hour of intermittent hemodialysis (HD).</div></div><div><h3>Methods</h3><div>A single-center retrospective cohort study was conducted of patient medical records in a remote dialysis center from January 2017 to July 2023. Adult patients with chronic kidney disease stage 5 on ≥3 months of intermittent HD who had received a course of vancomycin therapy with ≥1 serum vancomycin concentration recorded were included. Demographic and dosing data were collected. Clinician adherence with the dosing protocol and attainment of the therapeutic target (trough concentration within 15–20 mg/L) following the loading and maintenance doses were assessed. Factors associated with target nonattainment following the loading dose were analyzed, and the 48- and 72-h maintenance dosing intervals were analyzed for target nonattainment.</div></div><div><h3>Findings</h3><div>A total of 98 vancomycin courses (67 patients) were available for analysis. Only 38% of the loading doses were prescribed as per protocol. Following the loading dose, 25% of trough concentrations achieved the therapeutic target concentration (15–20 mg/L), 25% returned a supra-therapeutic concentration (&gt;20 mg/L) and 50% were sub-therapeutic (&lt;15 mg/L). When compared with those achieving target, sub-therapeutic concentrations were associated with a lower loading dose (median 16.6 vs 20.0 mg/kg, <em>P</em> &lt; 0.002), and supra-therapeutic concentrations had a shorter dosing interval between the loading dose and first maintenance dose (median 31.5 vs 39.0 h, <em>P</em> = 0.06). Of the 201 maintenance trough concentrations collected, 65% were therapeutic, 21% were sub-therapeutic and 14% were supra-therapeutic, with an overall median trough concentration of 17.3 mg/L. As the treatment duration increased, an increase was seen in the number of dose adjustments required to achieve the target trough concentration. The 48-h dosing interval was associated with more supra-therapeutic concentrations and the 72-h interval was associated with more sub-therapeutic concentrations (df = 2, <em>P</em> = 0.022).</div></div><div><h3>Implications</h3><div>We have identified a high rate of target nonattainment for HD patients on a three times a week vancomycin dosing regimen. We recommend a loading dose of 20 to 25 mg/kg irrespective of the indication and a better-defined dosing interval after the loading dose. A higher maintenance dose should be prescribed when the time to next dialysis session is 72 h. Further pharmacokinetic studies are needed to assess factors influencing target concentration attainment following the maintenance doses and to determine an optimal dosing regimen.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages e1-e7"},"PeriodicalIF":3.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058438","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":"Efficacy of Apheresis in the Remission of Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis","authors":"Nerea Moreno-Herraiz MSc ,&nbsp;Alicia Saz-Lara PhD ,&nbsp;Iván Cavero-Redondo PhD ,&nbsp;Carla Geovanna Lever-Megina MSc ,&nbsp;Óscar Martínez-Cifuentes MSc ,&nbsp;Iris Otero-Luis PhD","doi":"10.1016/j.clinthera.2024.12.016","DOIUrl":"10.1016/j.clinthera.2024.12.016","url":null,"abstract":"<div><h3>Purpose</h3><div>Sudden sensorineural hearing loss (SSHL) is an abrupt hearing loss, often of unknown cause. Apheresis is a treatment option aimed at improving blood hemorheology by removing pathogenic blood components. There are currently no previous meta-analyses on its efficacy. Therefore, the aim of this study was to evaluate the efficacy of apheresis in achieving total, complete, and partial remission of SSHL, as well as remission outcomes based on the type of apheresis used.</div></div><div><h3>Methods</h3><div>A systematic search was performed in PubMed, Scopus, Web of Science, and the Cochrane Library until March 2024. Random-effects models were used to calculate pooled estimates of treatment success rates (TSR) and their respective 95% CI to analyze the efficacy of apheresis in the remission of SSHL. Subgroup analyses were performed by type of apheresis (HELP-apheresis and rheopheresis).</div></div><div><h3>Findings</h3><div>The systematic review included 12 studies (10 in the meta-analysis) involving 786 adults with SSHL. The effect of apheresis showed significant total remission (TSR: 0.55; 95% CI: 0.47, 0.64), complete remission (TSR: 0.21; 95% CI: 0.11, 0.30), and partial remission (TSR: 0.43; 95% CI: 0.37, 0.48). Subgroup analysis revealed significant remission rates for HELP-apheresis (TSR: 0.58; 95% CI: 0.52, 0.64) and rheopheresis (TSR: 0.51; 95% CI: 0.30, 0.72).</div></div><div><h3>Implications</h3><div>These findings support apheresis as an equally or more effective treatment for SSHL, particularly in cases where corticosteroid therapy fails. However, due to the unknown etiology of SSHL, further clinical trials with larger, diverse populations are essential to confirm these results.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages 307-315"},"PeriodicalIF":3.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036936","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":"Efficacy of Oral Medication in Weight Loss Management: A Systematic Review and Network Meta-Analysis","authors":"Benedictus Benedictus MD ,&nbsp;Vincent Kurniawan Pratama MD ,&nbsp;Christopher William Purnomo MD ,&nbsp;Kenneth Tan MD ,&nbsp;Ratih Puspita Febrinasari MD, MSc, PhD","doi":"10.1016/j.clinthera.2024.12.013","DOIUrl":"10.1016/j.clinthera.2024.12.013","url":null,"abstract":"<div><h3>Purpose</h3><div>This systematic review was conducted to determine which type of oral medication for obesity provides the best weight loss effect.</div></div><div><h3>Methods</h3><div>This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline. For this systematic review, we used 3 databases for journal searches: PubMed, ScienceDirect, and Scopus. This study only included randomized controlled trials or open-label clinical trials. There was no year limit used in the journal search for this systematic review.</div></div><div><h3>Findings</h3><div>Eighteen randomized controlled trials, with a total population of 12,259 patients, were included. Of 18 studies, 15 were used for network meta-analysis. Based on the results of the network meta-analysis, weight loss was found in phentermine/topiramate (mean difference [MD], −3.28; 95% CI, −4.47 to −2.09), semaglutide (MD, −2.92; 95% CI, −4.38 to −1.46), phentermine (MD, −2.31; 95% CI, −3.82 to −0.81), naltrexone/bupropion (MD, −1.68; 95% CI, −2.87 to −0.49), topiramate (MD, −1.67; 95% CI, −2.86 to −0.48), and orlistat (MD, −1.44; 95% CI, −2.32 to −0.55). There were no significant differences among the groups. However, compared with placebo, all oral obesity therapies provide better benefits in weight loss (MD, −2.12; 95% CI, −2.64 to −1.59; <em>P</em> ≤ 0.00001).</div></div><div><h3>Implications</h3><div>Oral antiobesity drugs provide better weight loss than placebo. However, some side effects can be incurred by utilizing the drug for weight loss, especially related to the gastrointestinal system. Nonetheless, in clinical settings, consideration should be given to particular patients to reduce risk of side effects.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages 316-329"},"PeriodicalIF":3.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022481","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":"Physiologically Based Pharmacokinetic Modeling to Refine Dosing of Posaconazole in Young Children","authors":"Paul Malik PharmD, PhD ,&nbsp;Paola Mian PharmD, PhD","doi":"10.1016/j.clinthera.2024.12.018","DOIUrl":"10.1016/j.clinthera.2024.12.018","url":null,"abstract":"<div><h3>Purpose</h3><div>Posaconazole is a broad-spectrum antifungal for treating and preventing invasive fungal infections (IFIs) in immunocompromised individuals, including children as young as 2 years. Available in delayed-release (DR) oral suspension, intravenous formulation, and older immediate-release (IR) formulation (off-label in younger children), dosing harmonization across age groups and formulations remains inconsistent. This inconsistency arises from the unique physiology of young children and posaconazole's pH-dependent absorption. Limited pharmacokinetic (PK) data for children under 2 years complicates dosing, as absorption, distribution, metabolism, and excretion processes are underdeveloped and age-dependent. This work aims to harmonize pediatric dosing for children aged 2 to 7 years and extend dosing guidance for those aged 6 months to 2 years using physiologically-based PK (PBPK) modeling.</div></div><div><h3>Methods</h3><div>An adult PBPK model was created using posaconazole's physicochemical properties and ADME characteristics with virtual populations from PK-Sim. Calibrated with single-dose data from healthy subjects, the model was verified by predicting PK following multiple doses in adults at risk for IFIs. The model was then scaled to children, accounting for developmental anatomy and physiology, including UGT1A4 ontogeny. The pediatric model was evaluated against observed data from children aged 2 to 7 years. Simulations were conducted to harmonize dosing across formulations and extend dosing to children as young as 6 months, acknowledging standard plasma concentration targets for treatment of IFIs (1000 ng/mL) as well as prophylaxis (700 ng/mL).</div></div><div><h3>Findings</h3><div>The pediatric model adequately captured observed PK data from literature following all three formulations. The IR oral suspension is impractical and likely subtherapeutic for most children under 7 years due to solubility limits. Intravenous doses of 11–13 mg/kg once daily (QD) may be optimal for treatment, and 8 to 9 mg/kg QD for prophylaxis, varying by age. Oral DR suspension doses of 12 to 14 mg/kg QD for treatment and 8.5 to 10 mg/kg QD for prophylaxis may be optimal, also age-dependent. Dividing the total daily dose by a factor of 0.7 and administering twice daily can achieve similar trough levels.</div></div><div><h3>Implications</h3><div>PBPK modeling for posaconazole bridges the gap between PK principles and clinical practice, potentially improving therapeutic outcomes and minimizing risks associated with inadequate dosing in pediatric patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages 261-270"},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001614","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 Treatment Patterns Among US Patients With Type 2 Diabetes Mellitus Initiating Treatment With Once Weekly Semaglutide for Diabetes","authors":"Caroline Swift PhD, MPH ,&nbsp;Monica Frazer PhD ,&nbsp;Andrew Sargent MS ,&nbsp;Michael Leszko MPH ,&nbsp;Erin Buysman MS ,&nbsp;Noelle N. Gronroos PhD, MPH ,&nbsp;Sara Alvarez PharmD, MS ,&nbsp;Tyler J. Dunn PhD ,&nbsp;Josh Noone PhD","doi":"10.1016/j.clinthera.2024.12.014","DOIUrl":"10.1016/j.clinthera.2024.12.014","url":null,"abstract":"<div><h3>Purpose</h3><div>Injectable once weekly semaglutide for diabetes (OW sema) is a medication approved in 2017 for the treatment of patients with type 2 diabetes (T2DM). In clinical trials, OW sema has been shown to be effective at helping patients achieve glycemic targets. However, more data are needed to understand how patients who initiate treatment with OW sema are treated in the real world and to aid prescribers in making treatment decisions. This study characterized noninsulin antidiabetic medication use patterns among US patients with T2DM initiating treatment with OW sema.</div></div><div><h3>Methods</h3><div>In this retrospective, claims-based study, patients (15,588) were included if they had at least 1 claim for OW sema between January 1, 2018 and December 31, 2019, were at least 18 years old, were continuously enrolled in the health plan, and had at least 1 claim indicating a diagnosis of T2DM. All patients had at least 1 line of therapy (LOT) that started on the date of the first fill for OW sema. Data related to pre–index date demographics and clinical characteristics were collected, as were data on patient regimens and LOTs. The length of the LOT was calculated, and the top 10 noninsulin treatment regimens were reported in each LOT.</div></div><div><h3>Findings</h3><div>In the first LOT, OW sema monotherapy was the most common regimen. More than one third (36.5%) of patients had 1 LOT until the end of follow-up and most patients who had a second (52.1%) or third (72.0%) LOT continued it to the end of the study. Among the top 10 regimens, 42.2% of patients with a second LOT and 45.8% of patients with a third LOT had an LOT that included OW sema.</div></div><div><h3>Implications</h3><div>This study describes medication regimens within the first year of OW sema use. Among patients initiating OW sema, monotherapy was the most common regimen. These results provide insight into real-world usage patterns of this medication.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 4","pages":"Pages 277-283"},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001618","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":"Assessing Experiences With Trofinetide for Rett Syndrome: Interviews With Caregivers of Participants in Clinical Trials","authors":"Amy M. Barrett MSPH, MA ,&nbsp;Oyebimpe Olayinka-Amao PharmD, MPH ,&nbsp;Susan Martin MSPH ,&nbsp;Dilesh Doshi PharmD ,&nbsp;Kathie M. Bishop PhD ,&nbsp;James M. Youakim MD","doi":"10.1016/j.clinthera.2024.12.012","DOIUrl":"10.1016/j.clinthera.2024.12.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Rett syndrome (RTT) is a rare neurodevelopmental disorder that mainly affects girls and women. Trofinetide is approved for the treatment of RTT in adults and children aged ≥2 years. To gain insight into experiences with RTT and effects of trofinetide treatment at different stages of RTT, interviews with caregivers of individuals with RTT were conducted upon their exit from the open-label trofinetide trials.</div></div><div><h3>Methods</h3><div>Interviews were conducted with caregivers of participants in the LILAC/LILAC-2 open-label extension trials of the phase 3 LAVENDER trial in participants aged 5 to 20 years, and in DAFFODIL, an open-label trial in participants aged 2 to 4 years. Caregivers were asked about the RTT effects, experiences with trofinetide, meaningfulness of treatment effects, and satisfaction. Qualitative thematic analysis was performed.</div></div><div><h3>Findings</h3><div>Caregivers of 33 participants from the open-label trials were interviewed, including 26 from LILAC/LILAC-2 (mean age, 12.3 years) and 7 from DAFFODIL (mean age, 4.5 years). The most commonly reported effects of RTT in LILAC/LILAC-2 were no verbal communication (24/26 [92.3%]), unable to use hands (15/26 [57.7%]), repetitive hand movements (15/26 [57.7%]), unable to walk (15/26 [57.7%]), and seizures (14/26 [53.8%]). In DAFFODIL, the most commonly reported effects of RTT were no verbal communication (7/7 [100%]), impaired balance (4/7 [57.1%]), unable to use hands (3/7 [42.9%]), repetitive hand movements (3/7 [42.9%]), mood disturbance (3/7 [42.9%]), constipation (3/7 [42.9%]), and limited ability to use hands (3/7 [42.9%]). Caregivers most commonly reported improvements in hand use (11/26 [42.3%]), engagement with others (11/26 [42.3%]), eye gaze (8/26 [30.8%]), use of the Tobii eye tracking device (7/26 [26.9%]), and attention/focus/concentration (7/26 [26.9%]) in LILAC/LILAC-2. In DAFFODIL, caregivers reported improvements in new words (5/7 [71.4%]), hand use (4/7 [57.1%]), and eye contact (4/7 [57.1%]). Nearly all (31/32) caregivers were very satisfied or satisfied with trofinetide.</div></div><div><h3>Implications</h3><div>Caregivers of participants in open-label trofinetide trials reported improvements in RTT with meaningful impact in areas of motor function, communication, and engagement.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 181-188"},"PeriodicalIF":3.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001610","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":"Optimizing the Design of a Lateral Oscillating Device for Pressure Ulcer Prevention: Results of a Quasi-experimental Study","authors":"Ángeles Hernández Sánchez MSc ,&nbsp;Jesus M. Lavado-Garcia PhD ,&nbsp;Jesús M. Rodríguez-Rego PhD ,&nbsp;Laura Mendoza-Cerezo MSc ,&nbsp;Antonio Macías-García PhD","doi":"10.1016/j.clinthera.2024.12.009","DOIUrl":"10.1016/j.clinthera.2024.12.009","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study was to propose a lateral oscillating device for the prevention of pressure ulcers by understanding the mechanisms of tissue protection in healthy individuals during prolonged decubitus. We also sought to determine the optimal time interval for oscillation, considering peak pressure peaks and tolerable pressure limits as a function of individual characteristics such as age, weight, height, gender, and BMI.</div></div><div><h3>Methods</h3><div>A quasi-experimental, descriptive and analytical observational study was conducted between January 2022 and June 2023 with a sample of 25 healthy volunteers. Sacral, heel and trochanter pressure measurements were performed using sensors. Descriptive and bivariate statistical analyses were applied, and a linear regression model was used to analyze the relationship between independent variables and peak pressures recorded.</div></div><div><h3>Findings</h3><div>Peak pressure at the trochanter was significantly associated with age, weight and gender, while pressure at the sacrum showed a relationship only with gender. No significant associations were found for other variables. The 80th percentile was used to determine the maximum tolerable pressure, and the independent variables collectively explained 60% of the variance in maximum trochanter pressure (R² = 0.60; <em>p</em> = 0.0006). These findings helped to establish optimal time intervals for lateral oscillation, tailored to individual variability.</div></div><div><h3>Implications</h3><div>The designed lateral oscillating device proved to be effective in promoting tissue perfusion and reducing pressure build-up, thus contributing to pressure ulcer prevention. This personalized approach could significantly improve the care of immobilized patients in clinical settings.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages e1-e11"},"PeriodicalIF":3.2,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969343","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":"Health Care Resource Use and Medical Costs Among Patients With Major Depressive Disorder and Acute Suicidal Ideation or Behavior Initiated on Esketamine Nasal Spray or Traditional Treatments in the United States","authors":"Lisa Harding MD ,&nbsp;Maryia Zhdanava MA ,&nbsp;Amanda Teeple DrPH ,&nbsp;Aditi Shah MA ,&nbsp;Porpong Boonmak MA ,&nbsp;Dominic Pilon MA ,&nbsp;Kruti Joshi MPH","doi":"10.1016/j.clinthera.2024.12.006","DOIUrl":"10.1016/j.clinthera.2024.12.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Major depressive disorder with acute suicidal ideation or behavior (MDSI) is a substantial humanistic, economic, and clinical burden on patients. Data on health care resource use (HRU) and costs among patients with MDSI initiated on esketamine nasal spray relative to traditional treatments are limited. This study sought to describe HRU and medical costs of patients with MDSI initiated on esketamine, electroconvulsive therapy (ECT), antidepressant with second-generation antipsychotic (SGA) augmentation, and antidepressant monotherapy in the United States.</div></div><div><h3>Methods</h3><div>Adults with MDSI from Merative® MarketScan® Commercial Databases (January 2016 to January 2022) were categorized into esketamine, ECT, SGA augmentation, and antidepressant monotherapy cohorts based on treatments initiated on or after August 5, 2020 (index date). Baseline period spanned 12 months before index date; follow-up period spanned from the index date till the end of data/health plan eligibility. Acute care HRU (inpatient and emergency department days) and medical costs excluding index treatment costs were described per-patient-per-month among all cohorts.</div></div><div><h3>Findings</h3><div>The number of patients in the respective cohorts was 122 for esketamine, 336 for ECT, 9958 for SGA augmentation, and 4496 for antidepressant monotherapy. Across cohorts, mean patient age ranged from 29.1 to 41.2 years, and the majority of patients were female (range, 57.2%–65.6%). During the follow-up period, mean all-cause acute care HRU was 0.59 days in the esketamine cohort, which trended lower than in the ECT (3.17 days) and SGA augmentation (0.92 days) cohorts, and higher than in the antidepressant monotherapy cohort (0.32 days). Mean acute care HRU decreased from baseline in the esketamine, SGA augmentation, and antidepressant monotherapy cohorts by 58%, 21%, and 37% and increased in the ECT cohort by 44%. Mean follow-up medical costs per-patient-per-month were $1869 in the esketamine cohort, which trended lower than in the ECT ($4624) and SGA augmentation ($2163) cohorts, and higher than in the antidepressant monotherapy ($863) cohort. Relative to baseline, medical costs decreased in all cohorts (esketamine, 50%; ECT, 22%; SGA augmentation, 17%; antidepressant monotherapy, 32%).</div></div><div><h3>Implications</h3><div>Acute care HRU and medical costs trended lower among patients with MDSI initiated on esketamine nasal spray versus ECT or SGA augmentation; HRU and costs reduced most from pretreatment levels among patients treated with esketamine nasal spray versus patients treated with ECT, SGA augmentation, and antidepressant monotherapy. Results of this study may aid physicians in determining optimal treatments for the vulnerable MDSI population.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 189-195"},"PeriodicalIF":3.2,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930752","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":"Meta-Analysis of Randomized, Controlled Trials Assessing the Effectiveness and Safety of Biological Treatments in Chronic Obstructive Pulmonary Disease Patients","authors":"Khai-Chi Hu MD ,&nbsp;Min-Hsiang Chuang MD ,&nbsp;Chih-Cheng Lai MD ,&nbsp;Kuang-Ming Liao MD, PhD","doi":"10.1016/j.clinthera.2024.12.001","DOIUrl":"10.1016/j.clinthera.2024.12.001","url":null,"abstract":"<div><div>Anti-interleukin-5 (IL-5), anti-IL-5 receptor and anti-interleukin-4 (IL-4) have emerged as potential treatments for severe eosinophilic asthma, yet their role in treating chronic obstructive pulmonary disease (COPD) is unclear. A literature review was conducted up to May 31, 2024. Only randomized controlled trials (RCTs) assessing the clinical efficacy and adverse effects of biological treatment (anti-IL-5/ anti-IL-5 receptor /anti-IL-4) in COPD patients were included in this meta-analysis. Primary outcomes focused on COPD exacerbation risk, with secondary outcomes examining lung function, quality of life, and adverse events. Four articles comprising 6 RCTs were analyzed. Among 2837 patients receiving anti-IL-5/anti-IL-5 receptor therapies, 468 receiving anti-IL-4 therapies, and 1913 receiving placebo. Overall, biological treatment therapies collectively demonstrated a reduced risk of COPD exacerbation compared to placebo (rate ratio, 0.88; 95% CI, 0.80–0.97, I² = 53%). Specifically, dupilumab statistically significant reduction in exacerbation risk (rate ratio 0.70, 95% CI 0.58–0.84). Benralizumab showed a borderline reduction in exacerbation risk (rate ratio, 0.92; 95% CI, 0.85–1.00, I² = 0%, while Mepolizumab exhibited a trend towards lower exacerbation risk that did not reach statistical significance (rate ratio 0.90, 95% CI 0.77–1.06, I² = 62%). Subgroup analysis showed that patients with COPD and eosinophils ≥300 per cubic millimeter who received biological treatment may experience a reduced risk of acute exacerbation. Changes in lung function from baseline did not significantly differ between biological therapies and placebo. Analysis of St. George's Respiratory Questionnaire (SGRQ) scores indicated significant improvements with biological therapies compared to placebo (mean difference -1.30, 95% CI -2.46 to -0.14, I² = 28%). Biological therapies showed comparable risks of adverse events compared to placebo. This meta-analysis suggests that biological therapies may reduce the risk of acute exacerbations and improve quality of life in COPD patients compared to placebo. However, these therapies did not demonstrate significant improvements in pulmonary function. Future studies are needed to delineate the role of these biologic therapies in managing COPD exacerbations.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 226-234"},"PeriodicalIF":3.2,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930754","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":"Comparison of Effects on 6-Thioguanine Nucleotides According to Mesalazine Formulation in Pediatric Patients with Ulcerative Colitis","authors":"Hansol Kim MD,&nbsp;Yoon Zi Kim MD,&nbsp;Seon Young Kim MD,&nbsp;Yon Ho Choe MD, PhD,&nbsp;Mi Jin Kim MD, PhD","doi":"10.1016/j.clinthera.2024.12.007","DOIUrl":"10.1016/j.clinthera.2024.12.007","url":null,"abstract":"<div><h3>Purpose</h3><div>Mesalazine and thiopurines are important therapeutic agents for pediatric patients with ulcerative colitis (UC). Mesalazine, which may be administered in different forms depending on delivery mechanisms, can affect thiopurine metabolism, leading to increased 6-thioguanine nucleotides (6-TGN) levels. Therefore, when using these two drugs simultaneously, their interactions must be considered. This study aimed to analyze 6-TGN according to mesalazine formulation in pediatric patients with UC.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the data of 236 pediatric patients with UC who visited a single health center between January 2021 and December 2023. Among the enrolled patients, 198 were administered thiopurines, and of these, 136 underwent testing for 6-TGN.</div></div><div><h3>Findings</h3><div>The mean dose of azathioprine (AZA) was 0.66 mg/kg, and the mean 6-TGN level was 211.64 pmol/8 × 10^8 red blood cells (RBCs). The mean 6-TGN level for the group concurrently using time-dependent mesalazine and AZA was 245.00 pmol/8 × 10^8 RBCs, while that for the group concurrently using multimatrix mesalazine (MMX) and AZA was 141.97 pmol/8 × 10^8 RBCs (<em>P</em> &lt; 0.001). In the same patients, the mean 6-TGN level during time-dependent mesalazine treatment was 290.34 pmol/8 × 108 RBCs, whereas the mean 6-TGN level measured after switching to MMX was 148.54 pmol/8 × 108 RBCs (<em>P</em> = 0.016).</div></div><div><h3>Implications</h3><div>The group treated with MMX and AZA had a lower mean 6-TGN level than the group treated with time-dependent mesalazine and AZA. The mean 6-TGN level significantly decreased after switching from time-dependent mesalazine to MMX in the same patients. Therefore, when administering MMX, a higher dose of AZA is necessary to reach the target 6-TGN level, compared to the dose required when using time-dependent mesalazine.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 196-203"},"PeriodicalIF":3.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926831","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}