Current Medical Research and Opinion最新文献

{"title":"Comparative effectiveness of GLP-1 RAs and other glucose-lowering therapies among Medicare Advantage beneficiaries with T2D and ASCVD.","authors":"Xi Tan, Yuanjie Liang, Lin Xie, Cynthia Gutierrez, Joanna Harton, Chalak Muhammad, Caroline Swift, Adam de Havenon","doi":"10.1080/03007995.2025.2577762","DOIUrl":"https://doi.org/10.1080/03007995.2025.2577762","url":null,"abstract":"<p><strong>Objective: </strong>Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended as glucose-lowering therapies for people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Real-world evidence is limited comparing cardiovascular (CV) outcomes between once-weekly (OW) GLP-1 RAs versus other non-insulin glucose lowering therapies (ONIGLTs) including SGLT2is. This study aimed to compare CV outcomes among Medicare Advantage (MA) beneficiaries with T2D and ASCVD initiating OW GLP-1 RAs or ONIGLTs.</p><p><strong>Methods: </strong>This observational cohort study included MA beneficiaries with T2D and ASCVD within Optum's de-identified Clinformatics Data Mart Database (01/2007-03/2024). Propensity score matching was used to compare adults initiating OW GLP-1 RAs or ONIGLTs. Incidence rates and time to the first event of ischemic stroke (IS), myocardial infarction (MI), 2-, 3-, and 5-point major adverse cardiovascular event (MACE) during follow-up were assessed. Individual OW GLP-1 RAs were compared to SGLT2is.</p><p><strong>Results: </strong>Post matching, 41,835 adults were treated with OW GLP-1 RAs and 77,599 with ONIGLTs. Compared to ONIGLTs, OW GLP-1 RAs had 18% lower risk for IS, 14% lower for MI, 17% lower for 2-point MACE, 28% lower for 3-point MACE, and 27% lower for 5-point MACE. Compared to SGLT2is, OW GLP-1 RAs had 14% lower risk of 2-point MACE, 15% lower risk of 3-point MACE, and 14% lower risk of 5-point MACE. Semaglutide had lower risk of all CV outcomes versus SGLT2is.</p><p><strong>Conclusion: </strong>Among MA beneficiaries with T2D and ASCVD, risk of CV outcomes was lower with OW GLP-1 RAs, particularly semaglutide, versus ONIGLTs including SGLT2is.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343977","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":"Completing the colorectal cancer screening process: impact of eliminating cost-sharing for follow-up colonoscopy.","authors":"Mallik Greene, Quang A Le, A Burak Ozbay, Jordan J Karlitz, A Mark Fendrick","doi":"10.1080/03007995.2025.2577763","DOIUrl":"https://doi.org/10.1080/03007995.2025.2577763","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) screening is recommended for average-risk adults, yet completion of the screening process requires follow-up colonoscopy after a positive stool-based test (SBT). Until recently, patients frequently faced out-of-pocket costs for follow-up colonoscopy, which was classified as a diagnostic procedure. In November 2022, coordinated federal policies were issued to eliminate patient cost-sharing for this procedure across commercial and Medicare insurance, effective January 2023. This study evaluated changes in follow-up colonoscopy utilization before and after implementation of these policies.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using a large, nationally representative health care claims resource linked with laboratory data from January 1, 2022, to December 1, 2023. Adults aged 45-75 years who underwent colonoscopy were included. Follow-up colonoscopy (a diagnostic colonoscopy performed within six months of a positive SBT) was the primary endpoint. An interrupted time series design with a seasonally adjusted segmented autoregressive model estimated changes before (January-December 2022) and after (January-November 2023) cost-sharing elimination.</p><p><strong>Results: </strong>Among 10,841,411 individuals undergoing colonoscopy, follow-up procedures comprised 3.59% (95% CI, 3.18-3.99) before implementation. Following policy enactment, there was an immediate 41.2% relative increase (absolute increase 1.48% [95% CI, 1.25-1.71]; P < .001), sustained through November 2023.</p><p><strong>Conclusion: </strong>Elimination of patient cost-sharing for follow-up colonoscopy was associated with an immediate and sustained increase in utilization after positive stool-based tests. While other contextual factors may have contributed, these findings suggest that financial policy interventions can improve completion of the CRC screening process.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343978","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 insights into hyperkalemia burden and RAASi discontinuation: a cohort study.","authors":"Abdullah Hashim Almalki, Laila Fahd Sadagah, Reyan Hatem Merdad, Nourah Abdulaziz Alorainan, Salma Mohamed Abbas Quqandi, Muhjah Abdulhakim Bukhari, Fahad Ali Abdullah Dokhaikh","doi":"10.1080/03007995.2025.2579422","DOIUrl":"https://doi.org/10.1080/03007995.2025.2579422","url":null,"abstract":"<p><strong>Background: </strong>Hyperkalemia is a common and clinically significant complication among patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi). Despite their well-established cardiovascular and renal benefits, RAASi use is often limited by hyperkalemia, leading to treatment modification or discontinuation. Real-world adherence to potassium management strategies remains inconsistent, particularly in high-risk populations.</p><p><strong>Objective: </strong>This study aimed to determine the incidence and severity of hyperkalemia among RAASi users, identify associated risk groups, and assess its influence on clinical decisions and patient outcomes.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study involving 905 adult patients attending outpatient clinics at King Abdulaziz Medical City, Jeddah. All patients were on RAASi therapy and followed for a mean duration of 29.8 months.</p><p><strong>Results: </strong>Hyperkalemia (K⁺ ≥5.1 mmol/L) was observed in 295 patients, yielding an overall incidence of 32.8% (95% CI: 30-36%). Most cases were mild (74.6%), with moderate and severe hyperkalemia accounting for 19.0% and 6.4%, respectively. Recurrence occurred in over half of the affected patients, with decreasing intervals between successive episodes. Risk factors significantly associated with hyperkalemia included age ≥75 years, diabetes, congestive heart failure, and reduced eGFR. RAASi therapy was discontinued in 6.2%, and down-titrated in 4.5% of patients due to hyperkalemia. Adverse clinical events included emergency visits (2.1%), hospitalizations (1.7%), arrhythmias (0.3%), and dialysis (0.2%).</p><p><strong>Conclusion: </strong>Hyperkalemia affects nearly one-third of RAASi users, often prompting de-escalation of therapy. Proactive monitoring and management strategies are necessary to maintain the benefits of RAAS inhibition, especially in high-risk groups.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343979","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":"Patient and physician preferences among colorectal cancer screening tests: updated predictions from a discrete choice experiment.","authors":"A Mark Fendrick, Mallik Greene, A Burak Ozbay, Quang Le, Joseph W LeMaster, Rajab Idriss, Jeffrey Arroyo, Joseph C Anderson, Michael Dore, Matthew Quaife, Katelyn Cutts, Paul Limburg, Lila J Finney Rutten","doi":"10.1080/03007995.2025.2576596","DOIUrl":"https://doi.org/10.1080/03007995.2025.2576596","url":null,"abstract":"<p><strong>Objective: </strong>Colorectal cancer (CRC) screening rates fall short of national goals. This study aimed to understand eligible individuals' preferences regarding CRC screening modalities to improve screening adherence.</p><p><strong>Methods: </strong>Two cohorts took a discrete choice experiment survey: adults aged 45-75 years at average risk for CRC, and physicians who recommend CRC screening. Five attributes (test type, test frequency, true positive rate, true negative rate, adenoma true positive rate) from four different CRC screening modalities (cell-free DNA blood test [cf-DNA-BT], colonoscopy, fecal immunochemistry test [FIT], multi-target stool DNA [mt-sDNA] test) were assessed. Test-specific performance was derived from clinical data. Predicted choice probability (PrCP) of each modality was calculated from the results of a mixed logit model. Subgroup analyses were performed.</p><p><strong>Results: </strong>Among 1,249 adult respondents, mt-sDNA was the preferred modality (PrCP 39.4%) versus colonoscopy (24.8%), cf-DNA-BT (21.1%), and FIT (14.7%). In all subgroups, respondents preferred mt-sDNA. Respondents with previous noninvasive CRC screening experience (PrCP 53.5%) and with no prior CRC screening (42.1%) preferred mt-sDNA. PrCP for colonoscopy was lower for populations historically less likely to be adequately screened for CRC (such as 45-49-year-old respondents [PrCP 21.1%] and non-White respondents [23.1%]). PrCP among 400 physicians was highest for colonoscopy (PrCP 95.0%) versus mt-sDNA (4.3%), cf-DNA-BT (0.4%), and FIT (0.3%). No significant difference in preferences was found between primary care providers and gastroenterologists.</p><p><strong>Conclusion: </strong>US adults eligible for CRC screening preferred mt-sDNA testing over other screening modalities, while physicians highly preferred colonoscopy. Offering CRC screening options that align with patient preferences may result in higher screening adherence.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312563","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":"Exacerbation and myasthenic crisis in generalized myasthenia gravis: real-world healthcare resource utilization and cost burden in the United States.","authors":"Louis Jackson, Zhiwen Liu, Jacqueline Pesa, Alicia K Campbell, Zia Choudhry, Alberto E Batista, Nizar Souayah","doi":"10.1080/03007995.2025.2576597","DOIUrl":"https://doi.org/10.1080/03007995.2025.2576597","url":null,"abstract":"<p><strong>Objectives: </strong>Healthcare resource utilization (HCRU) and cost assessments for generalized myasthenia gravis (gMG) rarely include matched controls. HCRU and costs of acute MG-related events (MG exacerbation and myasthenic crisis) have been examined, but aggregation or comparison between studies is limited by heterogeneity. The study aim was to provide comprehensive, real-world data about gMG patients in the United States, including those experiencing MG-related events. A claims database analysis assessed (i) incremental HCRU and cost burden among adults with gMG versus non-gMG controls, (ii) occurrence of MG-related events, (iii) HCRU and cost burden of MG-related events, and (iv) factors associated with MG-related events.</p><p><strong>Methods: </strong>In this retrospective cohort study, adults with gMG in the United States were identified from Optum's de-identified Clinformatics® Data Mart Database (1/1/2017-3/31/2023). Rates of MG-related events during follow-up were calculated. Regression models assessed associations between occurrence of MG-related events and baseline demographic/clinical variables using a nested case-control design embedded within the existing gMG cohort. Incremental HCRU and healthcare costs were compared between cohorts with/without gMG using the propensity score method with inverse probability of treatment weighting for confounding controls. Incremental HCRU and healthcare costs were also reported for gMG subgroups with/without MG-related events.</p><p><strong>Results: </strong>Analyses included 16,561 gMG patients (12,813 prevalent and 3,748 incident) and 105,716 non-gMG controls. Among prevalent and incident gMG patients, respectively, MG exacerbation occurred during follow-up in 12.2% and 22.0% and myasthenic crisis in 6.0% and 12.4%. Patients with prior MG-related events were more likely to experience future events (odds ratio range 1.76-7.05). After weighting, gMG patients (median follow-up 696 days) experienced more frequent all-cause HCRU encounters and >4-fold higher healthcare costs ($5420 PPPM or ∼$65,000 per annum) versus non-gMG controls ($1,298 PPPM or ∼$15,500 per annum). Among MG patients, those with MG exacerbation/myasthenic crisis, respectively, experienced means of 3.02/3.35 hospitalizations, 1.91/2.13 emergency department encounters, 12.70/13.39 skilled nursing facility encounters, and 67.86/75.52 outpatient encounters during follow-up; associated costs were $17,113/$18,640 PPPM (or ∼$205,000/$224,000 per annum).</p><p><strong>Conclusion: </strong>The total healthcare cost of gMG was higher than some previous estimates at $5420 PPPM, driven primarily by inpatient care. MG exacerbation and myasthenic crisis occurred at a notable rate, could be recurrent, and were associated with high HCRU and costs. Findings can inform treatment decision-making with the aim of improving symptom control and reducing the likelihood of MG-related acute events.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-20"},"PeriodicalIF":2.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299026","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":"Differences in clinical trial and FDA approval datasets: implications for clinical and policy decision-making for noninvasive colorectal cancer screening tests.","authors":"Chyke A Doubeni, Chris Estes, A Mark Fendrick, John B Kisiel, Paul J Limburg","doi":"10.1080/03007995.2025.2576161","DOIUrl":"https://doi.org/10.1080/03007995.2025.2576161","url":null,"abstract":"<p><strong>Objective: </strong>The comparative effectiveness of clinical services may be inferred from concurrent studies in the same population, but such data are scarce. The U.S. Food and Drug Administration (FDA) creates a Summary of Safety and Effectiveness Data (SSED) to standardize population and performance characteristics for approved drugs and medical devices with the same or similar indicated use. Based on FDA approval requirements, SSED may differ from published clinical trial results. Previous studies reported the clinical implications of regulatory-associated data standardization for FDA-approved drugs, but to our knowledge, this has not been examined in medical devices.</p><p><strong>Methods: </strong>We evaluated the performance metrics of clinical trial data and FDA-approved datasets for noninvasive colorectal cancer screening tests including blood- and stool-based tests. Using a previously validated CRC screening microsimulation model in the US, we compared the lifetime impact of performance differences between the FDA and clinical trial data.</p><p><strong>Results: </strong>We found notable source-specific differences in reported performances for blood- and stool-based tests that significantly impacted modeled outcomes for CRC screening benefits, burden, and efficiency.</p><p><strong>Conclusion: </strong>These novel findings highlight the importance and impact of using standardized FDA data as the reference standard for comparative effectiveness studies, guideline recommendations, and other practice-informing activities.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The overlooked challenge of perioperative hypertension: unveiling pathophysiology and redefining management strategies.","authors":"Pandit Bagus Tri Saputra, Wynne Widarti, Sherly Yolanda, Ryan Arya Hidayat, Rendra Mahardhika Putra, Prihatma Kriswidyatomo, Novia Nurul Faizah, Firas Farisi Alkaff","doi":"10.1080/03007995.2025.2576594","DOIUrl":"https://doi.org/10.1080/03007995.2025.2576594","url":null,"abstract":"<p><p>Hypertension, defined as a systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, presents a significant challenge in perioperative settings. Perioperative hypertension-elevated BP occurring in preoperative, intraoperative, or postoperative phases-is highly prevalent, affecting 20-25% of patients undergoing non-cardiac procedures and up to 80% of those undergoing cardiac surgeries. This review aims to provide an in-depth examination of perioperative hypertension, emphasizing its impact on patient outcomes, current management strategies, and the need for standardized guidelines. This review synthesizes existing literature on perioperative hypertension, including its definitions, classifications, pathophysiology, and management approaches. Evidence from observational studies, clinical trials, and expert guidelines is analyzed to highlight gaps and best practices in perioperative BP control. A comprehensive literature review was conducted using scientific databases. Studies examining the incidence, complications, and management strategies of perioperative hypertension were included. Quantitative findings on the association between perioperative BP variations and clinical outcomes were also reviewed. Perioperative hypertension significantly increases the risk of adverse cardiovascular events, including myocardial infarction, stroke, and renal failure, contributing to longer hospital stays and higher healthcare costs. Patients with significant intraoperative systolic BP elevations had markedly higher risks of adverse outcomes, including approximately 1.5-fold higher mortality and a doubling of renal failure risk. Additionally, hypertension is a leading cause of elective surgery postponement. Despite its high prevalence, comprehensive management guidelines remain inadequate, resulting in inconsistent BP control strategies and suboptimal patient outcomes. The management of perioperative hypertension requires a more standardized and evidence-based approach. Current strategies emphasize individualized BP targets, optimization of antihypertensive therapy, and intraoperative hemodynamic stability. However, the lack of universally accepted guidelines hinders effective BP management. Future research should focus on developing standardized protocols to improve perioperative outcomes and reduce complications related to hypertension.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299050","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":"Closing the loop in colorectal cancer screening: real-world adherence to follow-up colonoscopy after positive mt-sDNA vs FIT/FOBT, stratified by payer type.","authors":"Mallik Greene, Brad Stieber, Joseph W LeMaster, Rajab Idriss, Igor Stukalin, Jorge Zapatier, Jeffrey Arroyo, Joseph Anderson, Jordan J Karlitz","doi":"10.1080/03007995.2025.2573654","DOIUrl":"https://doi.org/10.1080/03007995.2025.2573654","url":null,"abstract":"<p><strong>Introduction: </strong>A positive result from a multi-target stool DNA (mt-sDNA) test, fecal immunochemical test (FIT), or fecal occult blood test (FOBT) requires timely follow-up colonoscopy (FU-CY) to minimize colorectal cancer (CRC) incidence and reduce CRC-related mortality. To examine differences in FU-CY adherence between patients who received a positive mt-sDNA test or FIT/FOBT result by payer type.</p><p><strong>Methods: </strong>This retrospective analysis utilized a large national claims database linked to the Exact Sciences Laboratories database, which covers over 20 million individuals. Eligible patients were 45-75 years of age and had a positive result between 1/01/2017 and 6/30/2022, with the first test result serving as the index date. Primary outcomes included FU-CY adherence and time to colonoscopy completion.</p><p><strong>Results: </strong>A total of 362,646 (mt-sDNA n = 292,300; FIT/FOBT n = 70,346) patients with a positive result were identified during the study period. Overall adherence to FU-CY was significantly (<i>p</i><.001) higher for the mt-sDNA test cohort (77.1%) compared to the FIT/FOBT cohort (45.1%). By payer type, FU-CY adherence for patients in the mt-sDNA test cohort was highest in those covered by commercial insurance (80.7%) and lowest in those with Medicaid (69.8%); for patients in the FIT/FOBT cohort, commercial insurance coverage (42.3%) was lower than for other payer types (47.4-47.9%). In the regression analysis, FU-CY adherence was significantly (<i>p</i><.001) higher following screening with mt-sDNA than FIT/FOBT across payer types, sex, and race/ethnicity. Within 180 days, FU-CY rates across payer types were high ranging from 62.7%-74.9% following a positive mt-sDNA test, compared to 36.1%-42.5% observed for FIT/FOBT.</p><p><strong>Conclusion: </strong>In this large, comprehensive study combining two national databases, overall, as well as across each payer type, adherence to FU-CY was substantially higher in patients that initially screened with mt-sDNA compared with FIT/FOBT. In addition, FU-CY rates within 180 days were significantly higher in patients that had a positive mt-sDNA test.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-25"},"PeriodicalIF":2.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299023","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 Phase 2, multicenter, double-blind, randomized, placebo-controlled study of the safety and efficacy of forvisirvat (SP-624) in the treatment of adults with major depressive disorder.","authors":"Joel Raskin, Anita H Clayton, Susan G Kornstein, George I Papakostas, Yuki Prescott, Kelly Abernathy, John Hall, Michael Ackermann, William Wargin, Greg Rigdon, Valerie Arnold, Roberta Ball, Elan Cohen, Donald J Garcia, Mark DiBuono, Michael Downing, Otto Dueno, Beal Essink, Corinna Gamez, Haig Goenjian, Michael Greenbaum, Paul Gross, Willis Holloway, John Mark Joyce, George Konis, Jelena Kunovac, Mark Lerman, Elia Acevedo-Diaz, Mustafa Rawaf, Leon Rosenberg, Lara Shirikjian, Rishi Kakar, Felipe Suplicy, Drissana Tran, Nick Vatakis, Judith Joseph, James Knutson, Kurian Abraham, Lawrence Ginsberg, Gregory Mattingly, Eric Chavez, Saundra Maass-Robinson, Andrew Sedillo, Benny Barnhart","doi":"10.1080/03007995.2025.2574465","DOIUrl":"https://doi.org/10.1080/03007995.2025.2574465","url":null,"abstract":"<p><strong>Objective: </strong>Forvisirvat (SP-624) is an orally-administered epigenetic sirtuin 6 (SIRT6) activator with antidepressant effects in animal models that was well tolerated in three phase 1 trials in healthy adults. This phase 2 clinical study, SP-624-201, was designed to evaluate the safety and efficacy of forvisirvat 20 mg daily for 4 weeks in participants with major depressive disorder.</p><p><strong>Methods: </strong>SP-624-201 (NCT04479852) was a double-blind, placebo-controlled study. Participants were adults who met DSM-5 criteria for moderate to severe major depressive disorder, as confirmed by the Mini International Neuropsychiatric Interview. Participants receiving psychoactive medications or psychoactive supplements including antidepressants and mood stabilizers, were required to discontinue these medications and wait at least five half-lives of the medications before receiving forvisirvat. Primary endpoint was change from baseline to Week 4 in Montgomery Asberg Depression Rating Scale score. Participants were randomized to forvisirvat 20 mg daily (N = 163) or placebo (N = 156).</p><p><strong>Results: </strong>Of the 319 patients enrolled in the study, 319 (70.2%) were White and 211 (66.1%) were female. Mean age across subgroups ranged from 41.4 to 44.4 years. No significant difference in the primary endpoint was observed between treatment groups. However, the first post-hoc analysis conducted found that women treated with forvisirvat experienced significant overall improvement whereas men treated with forvisirvat did not. The difference between sexes was consistent for secondary efficacy measures as well. No serious adverse events were reported for forvisirvat-treated participants. The most frequent treatment-emergent event was headache (forvisirvat: 8.1%, placebo: 11.5%). Six of 163 forvisirvat-treated participants and 5 of 156 participants who received placebo discontinued due to adverse events.</p><p><strong>Conclusions: </strong>The novel epigenetic mechanism of action of forvisirvat, favorable safety profile, and consistent post-hoc efficacy results in women observed in this study support further development of forvisirvat. A phase 2b/3 trial of forvisirvat in major depressive disorder (NCT06254612), to confirm these results, is ongoing.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The validity of ICD-based codes to identify pediatric cases of congenital cytomegalovirus.","authors":"Sarah A Pollick, Kate L Wilson, Elizabeth C Lloyd, Sarah L Reeves, Megan H Pesch","doi":"10.1080/03007995.2025.2564340","DOIUrl":"10.1080/03007995.2025.2564340","url":null,"abstract":"<p><strong>Objective: </strong>Administrative claims databases are used to study the care of congenital cytomegalovirus (cCMV), yet the use of International Classification of Diseases, (ICD-9/10) codes for cCMV have not been validated. This study examines the accuracy of ICD-based codes for cCMV infection.</p><p><strong>Methods: </strong>Infants cared for at a quaternary children's hospital (2013-2023) that had an ICD-based diagnosis for cCMV or CMV Infection at ≤90 days of age were included. Medical record data was abstracted. True Positive cases were defined as those with an ICD code AND clinical and laboratory evidence consistent with cCMV. False Positive cases were defined as those with an ICD code without evidence of cCMV. Positive predictive value (PPV) and sensitivity for each diagnostic code at different age cutoffs were calculated within the cohort. Multinomial regression examined characteristics of the infant with odds of being a True Positive case of cCMV.</p><p><strong>Results: </strong>Of the 108 infants with ICD-9/10 codes for cCMV, 35% were false positives. PPV for ICD-9/10-CM codes for cCMV, CMV Infection, and Either code predicting actual cCMV were 0.86, 0.36, and 0.68 at age ≤45 days. PPV was the highest at ≤21 days of age, and for all codes sensitivity increased with patient age. Multinomial logistic regression found the age of the first diagnostic code ≤21 days (vs. >) (OR = 4.11, 95% CI 1.45-12.03), having an ICD-9/10-CM diagnostic code of cCMV (vs. CMV Infection) (OR = 10.87, 95% CI 3.64-32.47), and having Clinical Signs at Birth (vs. none) (OR = 8.4, 95% CI 2.72-25.81) to be associated with greater odds of having a True Positive case of cCMV (vs. Not cCMV).</p><p><strong>Conclusions: </strong>Administrative claims case definitions for cCMV were more likely to be accurate when assigned at a younger age. Studies using case definitions for cCMV that include the presence of codes for either cCMV or CMV Infection may be biased given the high proportion of false positives demonstrated in this study.</p>","PeriodicalId":10814,"journal":{"name":"Current Medical Research and Opinion","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257623","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}