Pharmacotherapy最新文献

{"title":"Pharmacotherapy research landscape and knowledge gaps of opioids in maternal and pediatric populations.","authors":"Aditi Shendre, Xiaofu Liu, ChienWei Chiang, Andrew Goodwin, Samuel-Richard Oteng, Jiezel A F Deypalubos, Shijun Zhang, Lei Wang, Jianing Liu, Mohammad Yaseen Abbasi, Blessed Winston Aruldhas, Syed Saoud Zaidi, Lindsey Marie Kirkpatrick, Lais Da Silva, Brian R Overholser, Aislinn M O'Kane, Prince J Kannankeril, Stephen W Patrick, Andrew D Wiese, Sara K Quinney, Lang Li","doi":"10.1002/phar.70024","DOIUrl":"https://doi.org/10.1002/phar.70024","url":null,"abstract":"<p><p>The use and misuse of opioids has surged in the past decade, with nearly half of the users being female. Although opioid use is lower among pregnant women, trends mirror the general population. While pediatric exposures largely occur through prescriptions. This review presents a novel landscape analysis of pharmacology knowledge gaps in opioids in the maternal and pediatric populations. We queried PubMed for studies on 27 opioids, focusing on pharmacokinetics (PK), and pharmacoepidemiology (PE) or clinical trials (CT) in maternal and pediatric populations. English-language publications were included, and data were synthesized to identify gaps. Additionally, MarketScan claims data and United States Food and Drug Administration (FDA) drug labels were analyzed to compare scientific evidence, opioid prescriptions/orders, and FDA recommendations. Morphine, fentanyl, methadone, and buprenorphine are the most researched opioids in PK and PE/CT literature in both populations, but hydrocodone, oxycodone, and codeine are the most prescribed. Nine opioids lack FDA labels, and four of the 18 labeled drugs lack any human data. Hydrocodone, oxycodone, and codeine labels include lactation-focused PK information, with some pediatric clinical data for the latter two. Seven opioids lack PK and PE/CT studies in the maternal population, and PK research is absent for seven opioids, and PE/CT data is lacking for eight opioids in the pediatric population. PK studies often focus on labor, delivery, and lactation accompanied by neonatal data, whereas pregnancy research mainly occurs in PE studies. In pediatric populations, study types are evenly distributed among children, but PE studies focus more on adolescents. Drug concentration is the most reported parameter in PK studies, and neonatal opioid withdrawal syndrome (NOWS) is a key outcome in both PK and PE studies. NOWS is also researched more using real-world data, whereas neurodevelopmental outcomes are often captured in prospective observational studies. There is substantial disparity between the most commonly researched and prescribed opioids. In particular, the opioid pharmacology knowledge gaps are larger in pregnant women and for the highly prescribed opioids hydrocodone and oxycodone. The limited human data in FDA labels underscores the need for additional studies. Studies using real-world data can potentially help address these gaps.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and pharmacodynamic evaluation of sulbactam-durlobactam in a critically ill patient on continuous venovenous hemofiltration infected with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex.","authors":"Wesley D Kufel, Nabil Zeineddine, Aliaa Fouad, Hanna F Roenfanz, Ryan K Shields, Ellen G Kline, Jameson Warner, Kathleen Hanrahan, Joseph L Kuti","doi":"10.1002/phar.70027","DOIUrl":"https://doi.org/10.1002/phar.70027","url":null,"abstract":"<p><strong>Background: </strong>Drug databases currently do not provide dosing guidance for sulbactam-durlobactam in continuous renal replacement therapy. Herein, we present the first in vivo pharmacokinetic (PK) evaluation of sulbactam-durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) bacteremia and ventilator-associated bacterial pneumonia (VABP).</p><p><strong>Methods: </strong>A 59-year-old critically ill patient (body mass index 60 kg/m²) required CVVH and developed CRAB bacteremia secondary to VABP. Sulbactam-durlobactam 2 g every 4 h infused over 3 h was initiated based on previous ex vivo data and the effluent rate of 6 L/h. The sulbactam-durlobactam minimum inhibitory concentration (MIC) was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed. Steady-state pre-filter blood, post-filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC).</p><p><strong>Results: </strong>The sulbactam-durlobactam MIC was 4/4 mcg/mL (susceptible). WGS revealed penicillin-binding protein (PBP)-1b and PBP-3 mutations. The selected dose exceeded sulbactam and durlobactam PK/pharmacodynamic (PD) targets with 100% free time above MIC (fT > MIC) and the ratio of area under the unbound concentration-time curve to MIC (fAUC/MIC) = 139, respectively. The SC for sulbactam and durlobactam was 0.68 and 0.67, respectively, and protein binding was 54% and 51%, respectively. Sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for CRAB bacteremia but recurred later in hospitalization 11 days after sulbactam-durlobactam treatment. The patient was ultimately transitioned to comfort care.</p><p><strong>Conclusion: </strong>Sulbactam-durlobactam monotherapy dosed at 2 g every 4 h (3-h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4/4 mcg/ml. Although sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of creatine monohydrate on motor function in children with facioscapulohumeral muscular dystrophy: A multicenter, randomized, double-blind placebo-controlled crossover trial.","authors":"Ian R Woodcock, Katy de Valle, Anita Cairns, Zoe E Davidson, Michael Kean, Nisha Varma, Anneke Grobler, David Metz, Kate Carroll, Nuran Dilek, Chad Heatwole, Monique M Ryan, Martin B Delatycki, Eppie M Yiu","doi":"10.1002/phar.70025","DOIUrl":"https://doi.org/10.1002/phar.70025","url":null,"abstract":"<p><strong>Background: </strong>Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individuals with muscular dystrophies but has not been tested in young people with FSHD. This study aimed to explore the efficacy of CrM on motor function in children with FSHD.</p><p><strong>Methods: </strong>In a randomized placebo-controlled double-blind crossover trial, powdered CrM at a dose of 100 mg/kg/day (maximum 10 g daily) was compared with placebo in two 12-week treatment periods with a 6-week washout between crossover arms. The primary outcome measure was the Motor Function Measure for Neuromuscular Disease (MFM-32) with secondary outcomes assessing safety, endurance, strength, patient-reported outcome measures, and muscle morphology measurements as assessed by whole-body magnetic resonance imaging (MRI).</p><p><strong>Results: </strong>Thirteen children were enrolled (mean (standard deviation, SD) 12.2 (2.67) years of age) and 11 patients completed both trial treatment periods. In an intention-to-treat analysis, no clinically meaningful difference was seen between treatment groups as measured by the mean difference in MFM-32 (0.19, 95% confidence interval (CI) -0.71 to 1.08). However, there was an improvement in 6-minute walk distance of 27.74 m (95% CI -1.41 to 56.88) and trends to improvement in the FSHD-Composite Outcome Measure for Pediatrics (FSHD-COM Peds), 10 meter walk/run, and in MRI measures. There were no serious adverse events. Serum creatinine increased by a mean 12.63 μmol/L (95% CI 1.14 to 24.12) post-CrM treatment, though this was presumed to reflect increased creatinine production. No participants discontinued CrM due to adverse events.</p><p><strong>Conclusion: </strong>CrM is safe and well tolerated in children with FSHD. Although CrM had no effect on motor function as measured by the MFM-32 compared with placebo, there were trends toward improvement in the 6-minute walk distance and other secondary outcome measures. This study confirms the feasibility of conducting clinical trials in children with FSHD. Further assessment of the efficacy of CrM in pediatric FSHD is warranted in a larger randomized controlled clinical trial. Future studies may benefit from stratifying population cohorts according to functional ability or by MRI fat infiltration measurements.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive performance of population pharmacokinetic models in InsightRX® for model-informed precision dosing for Cefepime.","authors":"Christina König, Joseph L Kuti, Andrew J Fratoni","doi":"10.1002/phar.70029","DOIUrl":"https://doi.org/10.1002/phar.70029","url":null,"abstract":"<p><strong>Background: </strong>Model-informed precision dosing (MIPD) is a promising tool used to ensure therapeutic antimicrobial concentrations. Model selection and sampling strategy might lead to different pharmacokinetic (PK) parameter estimates. Herein, we assess the predictive performance for cefepime PK in two models implemented within the InsightRX software using differing sampling approaches.</p><p><strong>Methods: </strong>Historic cefepime PK data and individual Bayesian estimates in predominantly critically ill patients, some of whom had extracorporeal support, served as the reference standard. Two population PK models (A; B) were evaluated using four sampling scenarios: (i) trough only, (ii) midpoint only, (iii) trough + midpoint, and (iv) peak + midpoint + trough. The median prediction error (MPE) and median absolute prediction error (MAPE) were calculated for clearance (CL) and volume of central compartment (V_c). Predicted categorical achievement of ≥70% time that the free drug concentration was greater than the minimum inhibitory concentration [fT>MIC_(8/16mg/L)] was compared.</p><p><strong>Results: </strong>MAPE and MPE for CL and V_c resulted in variability that was dependent on model and sampling strategy. Both models' overall MPE and MAPE for CL were <±20 and <30% for all tested scenarios, respectively, with a low MPE of -2.4% to 4.4% on CL for sampling scenario 4. For V_c, MPE and MAPE were >±20 and >30% for the majority of test scenarios across both models, respectively. When excluding patients with extracorporeal support, MPE/MAPE for V_c decreased to 3.7-4.8/23.3%-34.5% and -7.9-2.5/25.2%-29.6% for model A and B, respectively. Using each model and sampling scheme, only four patients had discordant predicted achievement of ≥70% fT>MIC_(8/16mg/L).</p><p><strong>Conclusions: </strong>These two population PK models and all sampling scenarios demonstrated acceptable prediction of cefepime PK parameters and pharmacodynamic exposures; therefore, they demonstrated suitability for utilizing MIPD for cefepime therapeutic drug monitoring.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton pump inhibitor concomitant use to prevent oxaliplatin-induced peripheral neuropathy: Clinical retrospective cohort study.","authors":"Keisuke Mine, Takehiro Kawashiri, Kohei Mori, Yusuke Mori, Haruna Ishida, Hibiki Kudamatsu, Shunsuke Fujita, Mayako Uchida, Takaaki Yamada, Nobuaki Egashira, Ichiro Ieiri, Satoru Koyanagi, Shigehiro Ohdo, Takao Shimazoe, Daisuke Kobayashi","doi":"10.1002/phar.70028","DOIUrl":"https://doi.org/10.1002/phar.70028","url":null,"abstract":"<p><strong>Background: </strong>Oxaliplatin-induced peripheral neuropathy (OIPN) is a major clinical challenge because it leads to discontinuation of chemotherapy. Omeprazole, a proton pump inhibitor (PPI), has been shown to prevent OIPN in a rat model. Therefore, we aimed to test whether the concomitant use of a PPI reduces oxaliplatin discontinuation due to OIPN.</p><p><strong>Methods: </strong>This retrospective study used data from 1015 patients who started treatment with oxaliplatin and evaluated two cohorts (PPI vs. non-PPI). The primary outcome measure was oxaliplatin discontinuation due to OIPN. A Kaplan-Meier curve was generated for cumulative doses and evaluated using the log-rank test and Cox proportional hazards analysis.</p><p><strong>Results: </strong>The log-rank test showed that the number of patients who discontinued oxaliplatin due to OIPN was significantly lower in the PPI group (p = 0.0264). Cox proportional hazards analysis incorporated and analyzed factors previously reported as potentially affecting neuropathy (sex, age, use of PPIs, calcium channel antagonists, opioids and adjuvant analgesics, and the CAPOX [capecitabine + oxaliplatin] regimen). The analysis suggested that the concomitant use of PPIs was a factor in reducing oxaliplatin discontinuation (adjusted hazard ratio [HR] = 0.568, 95% confidence interval [CI], 0.344-0.937, p = 0.0269). Since there were significant differences in some patient demographics between the two groups, propensity score matching was performed to align the patient demographics and then reanalyzed. After propensity score matching, the same analysis as above showed that oxaliplatin discontinuation due to OIPN was significantly less common in the PPI group (p = 0.0081); cox proportional hazards analysis showed that PPI use was a factor that significantly reduced oxaliplatin discontinuation due to OIPN (adjusted HR = 0.478, 95% CI, 0.273-0.836, p = 0.0096).</p><p><strong>Conclusions: </strong>These results suggest that concomitant PPI use may reduce oxaliplatin discontinuation due to OIPN in patients receiving oxaliplatin.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective cohort study of oral switch versus intravenous antibiotics for carbapenem-resistant enterobacterales and Pseudomonas aeruginosa infections on hospital discharge.","authors":"Christen J Arena, Ali Abed, Rachel M Kenney, Geehan Suleyman, Anita Shallal, Susan L Davis, Michael P Veve","doi":"10.1002/phar.70012","DOIUrl":"https://doi.org/10.1002/phar.70012","url":null,"abstract":"<p><strong>Objectives: </strong>To compare outcomes of oral switch versus intravenous antibiotics for the treatment of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) infections at hospital discharge.</p><p><strong>Methods: </strong>Institutional review board approved, retrospective cohort of adults infected with CRE or CRPA who received oral switch or intravenous antibiotics at hospital discharge from January 1, 2017, to April 30, 2024. Patients were included if they were eligible for oral switch and infected with an isolate susceptible to one or more oral antibiotics; non-bacteremic urinary tract infections were excluded. The primary outcome was 30-day clinical success at end of therapy, defined as lack of infection-related hospitalization, infection-related recurrence, or change/escalation of therapy. Secondary outcomes included hospital length of stay (LOS) and 30-day all-cause mortality from end of therapy.</p><p><strong>Results: </strong>Fifty-five patients were included; 51% received oral switch antibiotics and 49% received intravenous antibiotics. Thirty-three percent of patients had CRE, 67% had CRPA, and 38% of cultures were polymicrobial. The most common infection types were pneumonia (33%), intra-abdominal (26%), and bone/joint (22%). The median (interquartile range [IQR]) duration of outpatient therapy was 12 (6-25) days versus 20 (4-34) days for the oral switch and intravenous antibiotic groups, respectively (p = 0.341). 30-day clinical success was 61% in the oral switch and 48% in the intravenous antibiotic groups (p = 0.349); the median (IQR) hospital LOS for the oral switch and intravenous antibiotic groups was 14 (9-25) days and 16 (9-49) days, respectively (p = 0.165); 30-day mortality was 4% in the oral switch group and 15% in the intravenous antibiotic group (p = 0.193).</p><p><strong>Conclusion: </strong>A limited sample of patients who received oral switch antibiotics had similar outcomes to intravenous outpatient treatment of carbapenem-resistant organisms, with a shorter hospital LOS.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to comment on \"Association of atrial fibrillation with lamotrigine: An observational cohort study\".","authors":"Sodam Kim, Landon Welch, Bertha De Los Santos, Przemysław B Radwański, Mark A Munger, Kibum Kim","doi":"10.1002/phar.70016","DOIUrl":"https://doi.org/10.1002/phar.70016","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belzutifan's role in the treatment landscape of clear cell renal cell carcinoma.","authors":"Adrienne H Chen, Allison K Grana","doi":"10.1002/phar.70023","DOIUrl":"https://doi.org/10.1002/phar.70023","url":null,"abstract":"<p><p>The treatment of metastatic clear cell renal cell carcinoma (RCC) has changed significantly in the last 20 years with the advent of targeted therapies and immune checkpoint inhibitors. Belzutifan, a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, has a novel mechanism of action and was approved by the United States Food and Drug Administration (FDA) in 2023 for patients with advanced RCC. In the phase III LITESPARK-005 trial, patients receiving belzutifan had significant improvement in progression-free survival (PFS) compared with everolimus (PFS rate at 12 months: 33.4% vs. 17.1%; PFS rate at 18 months: 24.0% vs. 8.3%, respectively), as well as in objective response rate compared with everolimus (22.7% vs. 3.5%, respectively). There was no significant difference in median overall survival, with 21.4 months for belzutifan and 18.1 months for everolimus (hazard ratio [HR] 0.88; p = 0.20). In clinical practice, patients on belzutifan most often require intervention for anemia and hypoxia. This article describes the current preferred treatment options in clear cell RCC, the pharmacology of belzutifan, clinical trial data for belzutifan in clear cell RCC, our clinical experience with belzutifan and managing associated anemia and hypoxia, and future directions of belzutifan in RCC treatment.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of the revised anticholinergic drug scale with cultured cell-based serum anticholinergic activity and cognitive measures in older adults with mild cognitive impairment or remitted depression.","authors":"Ryan M Carnahan, Susmita Chandramouleeshwaran, Naba Ahsan, Roger Raymond, Jose N Nobrega, Wei Wang, Corinne E Fischer, Alastair J Flint, Nathan Herrmann, Sanjeev Kumar, Krista L Lanctôt, Linda Mah, Benoit H Mulsant, Bruce G Pollock, Tarek K Rajji","doi":"10.1002/phar.70022","DOIUrl":"https://doi.org/10.1002/phar.70022","url":null,"abstract":"<p><strong>Objective: </strong>The Anticholinergic Drug Scale (ADS) is a commonly used measure of anticholinergic exposure. This study describes an expanded and revised version of the ADS (rADS) and its relationship with cultured cell-based serum anticholinergic activity (cSAA) and cognitive measures.</p><p><strong>Study participants: </strong>Adults aged 60 years and older with mild cognitive impairment (MCI), remitted major depressive disorder (rMDD), or both, participate in the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.</p><p><strong>Study design: </strong>Cross-sectional investigation of data from the PACt-MD study.</p><p><strong>Measures: </strong>The rADS includes ratings for 1047 distinct products, about twice as many as the originally published scale; previously published ratings were revised for 40 drugs. Total rADS scores were calculated as sums of ratings of all drugs taken by participants; cSAA was measured in the participants' sera; cognitive performance included measures of executive function, language, processing speed, verbal memory, visuospatial memory, working memory, and an overall composite score.</p><p><strong>Statistical analysis: </strong>The relationship between rADS total scores and cSAA was examined using a Spearman rank correlation coefficient. Relationships between rADS total scores and cognitive performance measures were explored in multivariable linear regression models.</p><p><strong>Results: </strong>The sample included 310 participants (mean [standard deviation] age: 72 (6) years; 61.6% were women, and 81.6% had MCI [with or without rMDD]). Total rADS scores were positively correlated with cSAA (Spearman's correlation coefficient: 0.178, p = 0.0016). Total rADS scores were not significantly associated with cognitive performance.</p><p><strong>Conclusions: </strong>The revised scale is recommended as a replacement for the original ADS since it includes ratings for more drugs and was significantly, albeit weakly, associated with cSAA, similar to previous findings using the original ADS.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoroquinolones and the risk of aortic aneurysm or dissection: A population-based propensity score-matched German cohort study.","authors":"Julia Wicherski, Jonas Peltner, Cornelia Becker, Katrin Schüssel, Gabriela Brückner, Andreas Schlotmann, Helmut Schröder, Winfried V Kern, Britta Haenisch","doi":"10.1002/phar.70020","DOIUrl":"https://doi.org/10.1002/phar.70020","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk of aortic aneurysm or dissection associated with fluoroquinolone (FQ) prescription compared to macrolides in German routine health care data in order to replicate the recent study (Pharmacotherapy 2023;43:883) extending the results by contributing evidence for six additional broad-spectrum antibiotic classes as active comparators.</p><p><strong>Design: </strong>Cohort study in active comparator new user design comparing FQ with macrolides, tetracyclines, penicillins with extended spectrum, penicillins and beta-lactamase inhibitor combinations, second- and third-generation cephalosporins, sulfonamide and trimethoprim combinations, and lincosamides.</p><p><strong>Setting: </strong>German statutory health insurance, the \"Allgemeine Ortskrankenkasse\" (AOK), January 2013 to December 2019.</p><p><strong>Participants: </strong>Adults with at least one new prescription fill for FQ or active comparator antibiotics. New users were defined as individuals without antibiotic prescription fills, aortic aneurysm or dissection diagnoses, and hospitalization within 365 days prior to the cohort entry date. Users of FQ and active comparators were matched by nearest neighbor 1:1 propensity score matching.</p><p><strong>Main outcome measures: </strong>Incident inpatient aortic aneurysm or dissection was observed within a 60-day risk window. In sensitivity analyses, an extended risk window of 90 days was applied, and specific FQ agents, dosages, and diagnoses were stratified.</p><p><strong>Results: </strong>FQ episodes were associated with an increased risk for aortic aneurysm or dissection compared to macrolides (aHR = 1.52 [1.33; 1.74]), which replicates the risk estimate of Garg et al. (aHR = 1.34 [1.17; 1.54]). This association was robust in a 90-day risk window and for ciprofloxacin, levofloxacin, and moxifloxacin. Moxifloxacin comprised the greatest risk of aortic aneurysm or dissection compared to macrolides (aHR = 2.13 [1.64; 2.77]). Moreover, we observed similar associations when comparing FQ to tetracyclines, penicillins with extended spectrum, cephalosporins, and lincosamides (aHR = 1.86 [1.54; 2.24], aHR = 1.45 [1.28; 1.65], aHR = 1.23 [1.10; 1.37], and aHR = 1.73 [1.43; 2.11]), respectively.</p><p><strong>Conclusion: </strong>In a German cohort study, FQ use was associated with a 52% increased risk for aortic aneurysm or dissection within 60 days compared with macrolide use. The risk of FQ-associated aortic aneurysm or dissection compared to macrolides can be replicated in German routine health care data. Extending the analysis, we provided new insights that the effect size may depend on the chosen AC.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}