拜耳

Allergic rhinitis (AR) is an inflammatory condition that affects millions worldwide, causing significant healthcare costs and impairment in quality of life. While clinical guidelines recommend intranasal antihistamines as a first-line treatment for AR, current prescription azelastine hydrochloride 0.1

The article contains sections titled: 1 Introduction 2 Physical and Chemical Properties 3 Manufacture of Dithiocarbamate Salts 4 Transformation Products 4.1 Thiuram Sulfides 4.1.1 Thiuram Disulfides 4.1.2 Thiuram Monosulfides 4.1.3 Thiuram Trisulfides and Tetrasulfides 4.2 Thiocarbamoylsulfenamides 4.3 Thiocarbamoyl Chlorides 4.4 Dithiocarbamic Acid Esters 4.5 Heterocyclic Compounds 4.6 Other Derivatives 4.6.1 Dithiolanylium Salts 4.6.2 Alkylthioformimidic Chlorides 4.6.3 Isothiocyanates, Isocyanates, and Thioureas 4.7 Photolysis of Dithiocarbamates 5 Uses 5.1 Vulcanization Accelerators 5.2 Pesticides 5.3 Medical Applications 5.4 Radioprotective Agents 5.5 Imaging Technology 5.6 Other Uses 6 Toxicology and Occupational Health References

QuestionDoes the EMPEROR-Preserved prognostic model accurately stratify risk in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the FINEARTS-HF trial, and does baseline risk modify the treatment effect of finerenone?FindingsIn this secondary analysis of 6001 patients from the FINEARTS-HF trial, the risk model showed good discrimination and generally preserved calibration across mortality. The relative treatment effect of finerenone was consistent across all risk categories, while absolute risk reductions were greater among patients at higher baseline risk.MeaningIn this study, the EMPEROR-Preserved risk model provided a practical framework for risk stratification and estimation of absolute treatment benefit in patients with heart failure and mildly reduced or preserved ejection fraction and may support patient selection and enrichment in future clinical trials. This secondary analysis of a clinical trial evaluates whether a biomarker-based model estimates the risk of first heart failure hospitalization or cardiovascular death among patients with heart failure and mildly reduced or preserved ejection fraction and whether the treatment effects of finerenone vary by risk stratification. ImportancePatients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved EF (HFpEF) show substantial heterogeneity in prognosis.ObjectivesTo evaluate the performance of biomarker-driven prognostic models derived from the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) Trial in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to examine whether baseline risk modified the therapeutic effect of finerenone.Design, Setting, and ParticipantsThis is a prespecified secondary analysis of the FINEARTS-HF trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with symptomatic HF and left ventricular EF (LVEF) of 40% or greater. Patients were randomized between September 2020 and January 2023, and data analysis for this study was conducted from September to October 2025. The median (IQR) follow-up period was 32 (23-37) months.InterventionFinerenone (titrated to 20 mg or 40 mg) or placebo.Main Outcomes and MeasuresEMPEROR-Preserved risk scores for the outcomes of first HF hospitalization or cardiovascular death, cardiovascular death, and all-cause death were calculated in FINEARTS-HF using models incorporating N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, New York Heart Association functional class, history of chronic obstructive pulmonary disease and diabetes, insulin use, and-depending on outcome-age, hemoglobin and albumin levels, HF duration, time from prior HF hospitalization, and sodium-glucose transporter 2 inhibitor use. Estimated risks were compared with observed event rates, and model performance was assessed using Harrell C statistic. Treatment effects were evaluated across risk quintiles (Q1 to Q5) and across the continuous risk distribution.ResultsAmong 6001 patients (mean [SD] age, 72.0 [9.6] years; 2732 [45.5%] women; 3003 randomized to finerenone and 2998 randomized to placebo), the EMPEROR-Preserved risk model estimated risk of outcomes, with Q5 vs Q1 hazard ratios (HRs) of 10.49 (95% CI, 8.14-13.52) for the composite of HF hospitalization or cardiovascular death and 13.47 (95% CI, 8.79-20.64) for cardiovascular death. The model demonstrated good discrimination. The treatment effect of finerenone was consistent across risk quintiles for first HF hospitalization or cardiovascular death (Q1: HR, 0.93 [95% CI, 0.58-1.49]; Q2: HR, 1.04 [95% CI, 0.76-1.43]; Q3: HR, 0.82 [95% CI, 0.62-1.07]; Q4: HR, 0.81 [95% CI, 0.65-1.01]; and Q5: HR, 0.88 [95% CI, 0.74-1.05]; P for interaction = .68) and remained uniform across the continuous risk spectrum.Conclusions and RelevanceThe EMPEROR-Preserved risk models demonstrated good performance in FINEARTS-HF. Baseline risk did not modify the relative treatment effect of finerenone.Trial RegistrationClinicalTrials.gov Identifier: NCT04435626

This post hoc analysis of the FINEARTS-HF randomized clinical trial investigated if sudden deaths in patients with heart failure with mildly reduced or preserved ejection fraction are preceded by identifiable clinical deterioration compared with other modes of death. QuestionAre sudden deaths in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF) preceded by identifiable clinical deterioration compared with other modes of death?FindingsIn this post hoc analysis of the Finerenone Trial to Investigate the Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial including 6001 patients with HFmrEF or HFpEF, sudden death was preceded by modest worsening in New York Heart Association class, substantial declines in patient-reported health status, and rising N-terminal pro-B-type natriuretic peptide levels in the months before death, suggesting that many events may not have been entirely sudden or unexpected. Similar or more pronounced patterns were observed before other cardiovascular and noncardiovascular deaths.MeaningStudy findings reveal that although sudden death in HFmrEF or HFpEF is often preceded by clinical deterioration-suggesting that many events may not be entirely sudden or unexpected- these clinical signals lack specificity and are unlikely to meaningfully inform targeted prevention strategies. ImportanceSudden death remains a leading cause of mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF), but whether these events are preceded by clinical deterioration remains unclear.ObjectiveTo characterize clinical trajectories preceding sudden death in patients with HFmrEF or HFpEF and compare them with trajectories before other modes of death and survival.Design, Setting, and ParticipantsThis was a post hoc analysis of the Finerenone Trial to Investigate the Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial evaluating trajectories of functional status, patient-reported health status, and natriuretic peptide levels preceding adjudicated modes of death. This was a global, event-driven clinical trial. Patients with symptomatic HF, left ventricular EF of 40% or greater, New York Heart Association class (NYHA) II to IV, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were enrolled between September 14, 2020, and January 10, 2023. Data analysis was conducted in December 2025.InterventionsFinerenone vs placebo.Main Outcomes and MeasuresLongitudinal trajectories of NYHA class, Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), and NT-proBNP levels preceding sudden death were compared with trajectories in survivors and those who died of HF-related, nonsudden cardiovascular, or noncardiovascular causes, using linear mixed-effects models with restricted cubic splines.ResultsIncluded in this analysis were 6001 patients (mean [SD] age, 72.0 [9.6] years; 3269 male [54%]). Over a median (IQR) follow-up of 2.7 (1.9-3.0) years, 215 sudden deaths occurred. In the 6 months before death, sudden death was preceded by a slight worsening in physician-assigned NYHA class (from approximately 2.3 to 2.4), worsening self-reported health status (an approximately 8-point decline in KCCQ-TSS), and a gradual rise in NT-proBNP levels (from approximately 1800 to 2000 pg/mL). In contrast, among patients who survived, NYHA class improved (from approximately 2.3 to 2.1), KCCQ-TSS increased (from approximately 68 to 77), and NT-proBNP levels declined (from approximately 800 to 650 pg/mL) over the 18 months before the end of follow-up. Comparable patterns of deterioration to those preceding sudden death, often more pronounced, were observed before other modes of death.Conclusions and RelevanceResults of this post hoc analysis of the FINEARTS-HF randomized clinical trial reveal that in this contemporary HFmrEF or HFpEF cohort, sudden death was preceded by modest worsening of symptoms, declining quality of life, and rising natriuretic peptide levels, suggesting many of these events may not have been entirely sudden. However, similar deterioration preceding other modes of death suggests limited specificity for sudden death.Trial RegistrationClinicalTrials.gov Identifier: NCT04435626

Introduction Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies ( N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. Objective FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. Design FIONA (NCT05196035; Eudra-CT: 2021–002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m 2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021–002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. Conclusion FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. Trial registration ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.