Background:Myelodysplastic syndromes comprise a diverse group of hematopoietic stem-cell malignancies characterized by ineffective hematopoiesis, cytopenia, and increased risk of acute myeloid leukemia. Anemia is a common manifestation of lower-risk myelodysplastic syndrome (LR-MDS) and often necessitates red blood cell (RBC) transfusions, although reliance on transfusions is associated with adverse outcomes and substantial burden. This 28-year, single-center, retrospective study aimed to assess the burden of RBC transfusion-dependence (RBC-TD) in terms of healthcare resource utilization (HCRU), medical costs, and clinical outcomes among patients with LR-MDS in South Korea. Patients and Methods:Adult patients with LR-MDS initiating treatment between 1994 and 2022 at the Samsung Medical Center were included. HCRU, medical costs, and clinical outcomes were analyzed based on RBC-TD status. Results:Among 349 patients with LR-MDS, 103 (29.5%) were RBC-TD. RBC-TD was associated with increased HCRU and medical costs compared with non-transfusion-dependent (NTD) patients. Baseline erythropoietin (EPO) levels before erythropoiesis-stimulating agent (ESA) treatment were available for 76 patients with RBC-TD. Among 51 TD patients with baseline EPO levels ≤500U/L, 20 initiated ESA treatment after RBC-TD developed, to observe only limited effectiveness. Moreover, RBC-TD patients exhibited significantly shorter overall survival, leukemia-free survival and progression-free survival compared with NTD patients. Conclusion:RBC-TD in LR-MDS imposes significant clinical and economic burdens, including poor outcomes, heightened HCRU, elevated risks of disease progression, and premature mortality. These trends were particularly pronounced in patients with LR-MDS compared with the overall MDS population, underscoring that "lower-risk" does not necessarily equate to "lower-burden".
Purpose:Limited self-reported data on the real-world burden of idiopathic hypersomnia exist from a representative sample of the US general adult population. This study described the clinical, humanistic, and economic burden of adults with idiopathic hypersomnia compared to matched adults without idiopathic hypersomnia. Patients and Methods:This cross-sectional study used 2021 and 2023 US National Health and Wellness Survey data. Propensity score matching (1:2) was performed for adults (≥18 years) who self-reported a physician diagnosis of idiopathic hypersomnia and adults without idiopathic hypersomnia (non-idiopathic hypersomnia cohort). Post matching, outcomes were compared between cohorts using cluster-robust regression models; P values for primary outcomes were not adjusted for multiplicity. Results:Included were 163 adults with idiopathic hypersomnia (64.4% female, mean age 38.45 years) and 326 matched adults without idiopathic hypersomnia (66.0% female, mean age 39.60 years). The idiopathic hypersomnia cohort had higher prevalence of comorbidities (eg cardiovascular, cardiometabolic, sleep, psychiatric), higher mean Charlson comorbidity index scores (1.43 vs 0.34), and reported worse depression (PHQ-9) and anxiety (GAD-7) and poorer mental health, physical function (SF-36v2, RAND-36), and HRQoL (EQ-5D-5L, SF-6D, EQ-VAS) compared to the matched non-idiopathic hypersomnia cohort (P < 0.01). The idiopathic hypersomnia cohort reported more mean healthcare provider visits (13.34 vs 3.14), emergency department visits (0.88 vs 0.45), and hospitalizations (0.95 vs 0.35) in the past 6 months and higher annualized direct medical costs ($46,424.39 vs $14,700.21) than the matched non-idiopathic hypersomnia cohort (P < 0.05). The idiopathic hypersomnia cohort reported greater mean work productivity loss (49.07 vs 32.28) and activity impairment (48.22 vs 30.77), and annualized indirect costs ($15,269.22 vs $10,576.96) than the matched non-idiopathic hypersomnia cohort (P < 0.05). Conclusion:This study highlights the substantial real-world burden, including comorbidity, HRQoL, and economic, of idiopathic hypersomnia compared to the matched non-idiopathic hypersomnia cohort.
A focus group organised by the Drug Safety Research Unit (DSRU) International Working Group (IWG) on New Developments in Pharmacovigilance discussed current challenges and opportunities in pharmacovigilance (PV), emphasising the need for a multimodal approach in data analysis and accessibility of diverse data sources for drug safety surveillance. Nine participants, selected purposefully for their multisectoral expertise in PV, discussed the value of various data types, including data from clinical trials and real-world data (RWD), each offering distinct strengths and limitations. Key challenges identified included data standardisation, quality variability, technological barriers and ethical concerns, particularly with data derived from social media. Emerging tools such as knowledge graphs were highlighted for their potential to enhance data integration and signal detection, however further research is required. The group also addressed disparities in data access, with particular attention to regulatory restrictions, limited infrastructure in low-resource settings and restricted access to industry-held data. Proposed solutions included fostering greater data transparency, establishing secure data-sharing platforms and forming collaborative consortia to facilitate responsible and ethical data use. Overall, the discussion underscored the need for improved integration, access and methodological rigour to strengthen PV practices and enhance global drug safety monitoring.
This paper presents locating oscillation sources in inverter-based resource (IBR) integrated systems using the oscillation flow approach. The oscillation active or reactive power flow is used as an index of passivity at a particular frequency, which is computed based on the voltage and exporting current phasors of the oscillation frequencies at the IBR point of interconnection. The oscillation power flow direction indicates the oscillation source location against the measurement point. This method is applicable when the system has a dominant natural oscillation mode in either the abc phase voltage and current or the root mean square (RMS) magnitudes. The method has been tested for four types of oscillations: subsynchronous oscillations due to a type-3 wind farm with radial connection to series compensation, low-frequency weak grid oscillations, phase-locked-loop (PLL)-induced oscillations, and plant control delay caused voltage-var oscillations. The oscillation power flow computed in either the static or the dq frame is able to detect and locate the oscillation sources in all three scenarios. Additionally, two forced oscillation scenarios are presented to demonstrate the application scope for this method.
Background:Major depressive disorder (MDD) is a serious mental illness and leading cause of disability. MDD is highly comorbid with physical illnesses such as cardiovascular disease (CVD) and diabetes mellitus (DM). Sertraline, a selective serotonin reuptake inhibitor, is proven effective and well-tolerated in clinical trials, and is recommended among first-line treatment options for MDD. Methods:This study explored the effectiveness and acceptability of sertraline in real-world clinical practice, utilizing electronic health record-derived, de-identified data from NeuroBlu Data in the USA. All-cause sertraline discontinuation was the main outcome, with change in Clinical Global Impressions Severity (CGI-S) serving as a secondary outcome. Results:All-cause discontinuation was assessed in 2948 patients treated with sertraline for MDD (702 comorbid with CVD and 280 with DM). The cumulative discontinuation rates at 2- and 3-month follow-up time points were 16.9% and 24.8%, respectively. No significant differences were observed between males and females or those with and without CVD or DM. Change in CGI-S was assessed in 713 patients who had data for one or more follow-up assessments conducted between 2 to 24 months after sertraline prescription. About 9% to 17% of patients demonstrated clinically substantial improvement in CGI-S (decrease by ≥2) across follow-up time points, while 74% to 88% showed little or no change. A sensitivity analysis showed clinically meaningful improvement in CGI-S (decrease by ≥1) in 19% to 36% of patients, with 54% to 69% showing no change. Patients with greater illness severity at baseline were more likely to experience improvement. Conclusion:This study demonstrates that all-cause discontinuation rates in routine practice were consistent with clinical trials indicating comparable sertraline treatment acceptability. The findings add to the body of evidence on real-world effectiveness and clinical utility of sertraline in patients with MDD with or without comorbid chronic medical illnesses like CVD and DM.
