The real-world experience of biologics for neuromyelitis optica spectrum disorders as first-line and switched therapy.

The concept of virtual clinical trials: A game changer in radiation oncology research?

ABSTRACT Background: Natural disasters are known to affect the mental health of the victims; however, the understanding of their impact on real-world clinical practice remains insufficient. Objective: This study aimed to evaluate the effects of the 2018 Japan floods, one of the largest disasters in Japan’s recorded history, on antidepressant prescriptions over time. Method: Prescription data from the medical insurance claims database covering three prefectures that accounted for 90% of flood damage were analyzed for the years before and after the floods. Participants were categorized as disaster victims or nonvictims based on local government designations. A difference-in-differences analysis compared the trends in antidepressant prescriptions between victims and non-victims during the period surrounding the floods. Results: Of 5,000,129 participants, 31,235 were disaster victims. Victims were more likely to be prescribed antidepressants after the disaster than nonvictims (p < .001). This trend peaked 2–3 months after the disaster (adjusted Ratio of Odds Ratios [ROR], 1.13; 95% confidence interval [CI] 1.07–1.20) and persisted up to 1 year later (adjusted ROR, 1.20; 95% CI 1.12–1.28). Among antidepressants, noradrenergic and specific serotonergic antidepressants (NaSSAs) and serotonin antagonist and reuptake inhibitors (adjusted ROR 1.47, 1.49; 95% CI 1.21–1.80, 1.22–1.83) were particularly prescribed more frequently among victims. When limited to those who had not used antidepressants before the disaster, NaSSAs (adjusted ROR 2.56; 95% CI 2.14–3.07, p < .001) were conspicuously more prescribed. Conclusions: The floods were associated with an increase in antidepressant prescriptions, suggesting the development of disaster-related mental health conditions such as depression and post-traumatic stress disorder. The need for care became pronounced 2–3 months after the event and persisted for 1 year. These findings highlight the need for psychiatric drug treatment among disaster victims and emphasize the importance of identifying appropriate timing for such interventions.

Background: it is well known that improving clinical guidelines should take into account the results of studies conducted in real-world clinical practice. Data of the prescription patterns and dosages of antipsychotic medications in patients with schizophrenia of varying disease duration are in the area of special interest. The aim was to study the relationship between the prescription patterns of antipsychotics and the socio-demographic, clinical and dynamic characteristics, quality of life indicators, and social functioning of patients with paranoid schizophrenia. Patients and Methods: the study included 208 inpatients with paranoid schizophrenia (total sample; mean age — 30.21 ± 6.84 years, males — 58.65% ( n = 122)). The structure of antipsychotic prescriptions was analyzed based on medical records from 2018 to 2024. For all medications, the standard daily dose was determined using the Defined Daily Dose (WHO) methodology. Socio-demographic, clinical and dynamic characteristics were assessed, along with PANSS, BACS, PSP, and WHOQOL-BREF scale scores. Results: a total of 16 antipsychotic drugs were identified in the prescription structure. Two patient groups were identified in the principal component space. Group 1 included patients with a significant (&gt; 60%) predominance of risperidone and olanzapine prescriptions ( n = 136). Group 2 made up patients with a comparable predominance of haloperidol and clozapine prescriptions ( n = 72). Group 1 included 94 (69.1%) patients experiencing their first psychotic episode, whereas Group 2 included 50 (69.4%) chronic patients. Group 1 had significantly lower disease duration, number of hospitalizations ( p &lt; 0.001), number of disabilities ( p = 0.003); significantly higher mean duration of outpatient treatment ( p &lt; 0.001), higher scores on the BACS subtests “verbal learning” ( p = 0.009) and “working memory” ( p = 0.049). Conclusion: risperidone, olanzapine, and other second-generation antipsychotics are significantly more frequently prescribed in real-world clinical practice to patients with shorter disease duration and relatively preserved cognitive functions. In contrast, haloperidol and clozapine predominate in the prescriptions of chronic patients.

BackgroundMirtazapine is a pharmacological agent commonly utilized as a first-line treatment for major depressive disorder, exhibiting both noradrenergic and selective serotonergic activity. Currently, there is an absence of a comprehensive and systematic review of the adverse events (AEs) associated with mirtazapine. Consequently, this study aims to assess the safety profile of mirtazapine in real-world clinical practice by performing an in-depth analysis of data from the Food and Drug Administration’s Adverse Event Reporting System (FAERS).MethodsThis study collected all real-world adverse event data related to mirtazapine from the FAERS database spanning from Q1 2004 to Q4 2024. Disproportionality analysis methods were employed, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS), to assess the associations between mirtazapine and major medical events.ResultsOur study identified a total of 14,237 adverse event reports related to mirtazapine from the FAERS database, of which 2,954 had available data. The results identified several previously unreported adverse events, including prolonged QT interval on electrocardiogram, insomnia, coma, falls, and drug toxicity. AEs related to mirtazapine occurred across 27 system organ classes (SOCs), primarily including Nervous System Disorders, Investigations, and Surgical and Medical Procedures. The onset of adverse events typically occurred within one month of mirtazapine administration, though it is important to note that the risk of AEs persists even in the following year.ConclusionOur research findings are consistent with clinical observations. Additionally, we have identified new adverse reactions related to mirtazapine. These results provide valuable evidence for further guiding safety research on mirtazapine. They also help clinicians place greater emphasis on monitoring its AEs during use.

Antiplatelet therapy, which consists primarily of aspirin (acetylsalicylic acid) and P2Y12 receptor antagonists, is one of the most commonly prescribed treatments in current clinical practice, because of the steadily increasing incidence of cardiovascular disease and the related high mortality rates. Antiplatelet agents are valuable tools for physicians because they can prevent atherothrombotic events, improve clinical outcomes, and reduce cardiovascular mortality rates in primary and secondary prevention. However, secondary bleeding remains a concern with antiplatelet therapy. The current goal of medical science is to minimize bleeding risk in patients at high risk for hemorrhagic events. This review presents data on antiplatelet drugs used in real-world clinical practice. It provides detailed, comprehensive descriptions of their use in various situations and highlights strategies for switching between them. The review also discusses the consequences of high residual platelet reactivity after treatment and summarizes current trends in patient-centered medicine. Additionally, the work revealed the high potential for developing effective and safe agents to counteract the effects of antiplatelet agents. New antiplatelet agents are being developed, such as selatogrel, revacept, and glenzocimab. Further research is required to understand how these potential new agents will integrate into the current antiplatelet therapy paradigm and whether they will promote safer clinical practices. Although significant advances in optimizing antiplatelet therapy have been made through clinical studies, more work is yet to be done. Most genetic intervention studies focus on CYP2C19 polymorphisms in order to personalize antiplatelet treatment strategies.

Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease that requires long-term glycemic control. The long-term real-world evidence for glucagon-like peptide-1 receptor agonists remains limited. This study aimed to evaluate the sustained glycemic and weight-lowering effects of dulaglutide in patients with T2DM who had maintained therapy for at least 3 years. This retrospective cohort study analyzed 403 patients with T2DM who were treated continuously with weekly doses of dulaglutide for ≥ 3 years between 2016 and 2023 at a single tertiary hospital. Baseline and follow-up data on glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were also assessed. The participants had a mean age of 60.0 years, with a mean diabetes duration of 17.4 years. Over a mean follow-up of 4.3 years, HbA1c decreased from 8.7% (72 mmol/mol) to 7.6% (60 mmol/mol), reflecting a mean reduction of 1.1% (12 mmol/mol) (p < 0.001), and body weight decreased by 2.9 kg (p < 0.001). Baseline HbA1c level was the strongest predictor of glycemic improvement. Dulaglutide provided durable improvements in glycemic control and weight reduction for more than 3 years, even in patients with long-standing T2DM and comorbidities. These results support its role as a long-term treatment option in real-world clinical practice.

Machine-learning-based decision-tree model for patients with single-large hepatocellular carcinoma.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with impaired quality of life and a substantial burden of disease. Lebrikizumab is a monoclonal antibody that selectively binds with high affinity to interleukin-13, thereby inhibiting its cascade signaling and reducing inflammation. Lebrikizumab has demonstrated efficacy and safety in adults and adolescents ≥ 12years with moderate-to-severe AD in randomized, placebo-controlled, phase3 clinical trials. Here, we report a case series of four patients with moderate-to-severe AD who transitioned to lebrikizumab treatment in the Czech Republic. All four patients had failed previous targeted therapies (biologics or Janus kinase inhibitors) and/or cyclosporine treatments and presented with associated comorbidities. After 12 to 16weeks of treatment with lebrikizumab, clinically significant improvements in signs and symptoms (assessed by Eczema Area and Severity Index [EASI], pruritus Numerical Rate Scale, quality of life assessed by the Dermatology Life Quality Index [DLQI], and/or Patient Oriented Eczema Measure [POEM]) were reported. The results of these four clinical cases support the effectiveness observed in randomized clinical trials and suggest that lebrikizumab may be an effective treatment for moderate-severe AD in real-world clinical practice, even in patients with comorbidities who have failed previous advanced treatments.

Safety and Efficacy of Bimekizumab in Patients With Moderate-to-Severe Hidradenitis Suppurativa: A Multicenter Retrospective Cohort Study.

To evaluate the clinical outcomes of the switch to faricimab in a treat-and-extend (T&E) regimen patients with neovascular age-related macular degeneration (nAMD). This prospective cohort study included consecutive patients with nAMD who had previously been treated with anti-VEGF agents in a T&E regimen, with treatment intervals (TI) that could not be extended beyond 12 weeks, and a minimum follow-up of 24 weeks. These patients were switched to faricimab therapy in a T&E regimen for at least 6 months. The primary endpoint was the TI between intravitreal injections (IVIs), and the secondary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to the last follow-up visit (LFUV). A total of 225 eyes from 188 patients were included, with a mean age of 79.6 ± 7.4 years. Previous anti-VEGF treatments included ranibizumab (n = 34), aflibercept (n = 144), brolucizumab (n = 6), and bevacizumab (n = 41). TI1 (5.9 ± 2.0 weeks) matched the prior treatment interval. Significant increases in treatment intervals were observed at subsequent time points (TI2: 8.2 ± 3.2 weeks, TI3: 10.1 ± 3.9 weeks, TI4: 10.7 ± 4.3 weeks, TI5: 9.9 ± 4.0 weeks, and TI6: 8.5 ± 4.4 weeks; p < 0.001). BCVA remained stable, going from 0.41 ± 0.23 to 0.43 ± 0.24 (p = 0.0112). The mean number of injections was 5.9 ± 1.9, with a mean follow-up duration of 51.4 ± 11.8 weeks. The switch to faricimab in a T&E regimen significantly increased treatment intervals maintaining BCVA in patients with nAMD under other anti-VEGF treatments. No serious adverse events were reported. Longer follow-up is needed to confirm these results.

With the growing global threat of coronary artery disease (CAD), automated CAD diagnosis techniques based on coronary CT angiography (CCTA) have been developed. However, their clinical applicability remains limited due to the heterogeneity of stenosis and plaque attributes, as well as confounders within the causal relationships of CAD diagnosis. This work introduces the Attribute-Decoupled Intervention Network (ADI-Net), a confounder-free CAD diagnosis framework designed for fine-grained analysis at both the artery and patient levels, aligning with real-world clinical practice. ADI-Net employs an attribute-decoupled representation that effectively captures the heterogeneous features of stenosis and plaque with differential constraints, enabling precise, fine-grained classification. Additionally, the dynamic-updating causal intervention continuously refines confounder banks and applies the Do-expression within a complete causality, ensuring comprehensive, cross-level assessments. Experiments on CCTA datasets from three clinical centers demonstrate that ADI-Net outperforms state-of-the-art methods in cross-level, fine-grained CAD diagnosis, exhibiting superior robustness, domain adaptability, and data efficiency.

Pulsed field ablation (PFA) for the treatment of atrial fibrillation offers potential safety benefits compared to thermal ablation modalities. However, the high voltage electric pulses required to irreversibly electroporate myocardial cells present a unique clinical challenge in regard to patients with cardiac implantable electronic devices (CIEDs). The strong electric fields of PFA can induce voltages and currents in CIED leads, which may result in electromagnetic interference (EMI) or even permanent damage to the device itself, requiring reset or replacement. Limited evidence exists on PFA procedures in patients with CIEDs. Historically, clinical trials have excluded patients with CIEDs, which leaves evidence from real-world clinical practice to fill this critical evidence gap. This review describes the potential hazards when performing PFA in patients with CIEDs, current real-world evidence in such patients, and recommended workflows to mitigate risk and prioritize patient safety.

The purpose of this analysis is to report on the clinical efficacy of Continuous Diffusion of Oxygen (CDO) therapy in real-world clinical practice and compare those results to data published in controlled clinical studies. For the real-world clinical results, a Prospective Patients Database (PPD) of 764 patients treated using CDO therapy in a broad range of clinical practices across a wide range of wound types and wound locations was analyzed. The objectives included analyzing the clinical efficacy of CDO therapy across multiple wound types and anatomical locations, testing the data for robustness, and comparing the efficacy to results from controlled clinical studies for CDO and NPWT. The PPD data is also analyzed for efficacy among the sexes and by age for older patients in the Medicare population. The robustness of the PPD data is tested using various non- and semi-parametric statistical tools, including the Kaplan–Meier and Cox proportional hazard (PH) models, among others. The results show that CDO therapy is highly efficacious with an average healing success rate of 76.3% in real-world application, ranging from 71.2% to 84.1% for different wound types. The Medicare age population had an average age of 78 years old and similar healing rates to the overall population, with slightly better results for pressure ulcers in the older patient population. The PPD data proved to be extremely robust in every test method, demonstrating substantially equivalent efficacy in various wound types and locations, as well as between men and women. The PPD results for CDO compared favorably to clinical trial results for CDO and NPWT. Both clinical trial and PPD data for CDO exhibited better healing rates when compared to NPWT. Kaplan–Meier analysis shows that CDO use in clinical practice has 79.2% full closure in 112 days, as compared to NPWT, which has 43.2% full closure in the same timeframe for similar wound sizes and severity. These results demonstrate not only that CDO is highly efficacious in clinical practice, but that the efficacy is also similar across all wound types and locations in the body. CDO also compares very favorably to NPWT.

Purpose Entrustable professional activities (EPAs) for entry into residency often remain broad and underspecified and lack alignment with the clinical contexts that medical graduates encounter. This study aims to identify chief complaints that can serve as context anchors for EPAs for entry into residency. Methods A structured, expert consensus survey was conducted in 2024 at Charité—Universitätsmedizin Berlin, Germany. In total, 192 participants from four groups (senior medical students, hospital residents, hospital specialists, and general practitioners) rated 134 chief complaints. An 80% threshold was set to define a consensus on the relevance of complaints for autonomous differential diagnostic work-up by new residents under supervision level 3b. Results Forty-four chief complaints (33%) reached the consensus threshold, with abdominal pain, dyspnoea, fever and cough receiving the highest agreement (>97%). Strong consistency was observed across expert groups, with all four groups agreeing on 35 complaints. For the remaining nine, only minor variations were observed, with generally only one expert group falling below the 80% threshold. Conclusions Defining core chief complaints offers a practical approach to contextualize undergraduate EPAs, thereby bridging the gap between educational expectations and real-world clinical practice. These findings support curriculum alignment and entrustment decisions while promoting trainees’ readiness for early postgraduate training.

No clinical trials demonstrated anti-HER2 plus chemotherapy (anti-HER2 + ChT) was superior to anti-HER2 plus endocrine therapy (anti-HER2 + ET) in HR + /HER2 + MBC. This study aims to compare efficacy of anti-HER2 + ET with anti-HER2 + ChT in real-world clinical practice, and analyze clinical outcome of anti-HER2 + ET as maintenance therapy after benefiting from anti-HER2 + ChT. This study retrospectively compared two regimens: anti-HER2 + ChT vs anti-HER2 + ET, utilizing chi-square tests for response rate comparisons and Kaplan-Meier approach for survival analysis. Totally, 241 eligible patients were included in this study. In first-line setting, 197 patients (81.7%) received anti-HER2 + ChT and 44 (18.3%) received anti-HER2 + ET. Objective response rate (54.3% vs 11.4%, P < 0.001) and clinical benefit rate (82.7% vs 68.2%, P = 0.029) of anti-HER2 + ChT group were higher than those of anti-HER2 + ET. PFS analysis showed there was no significant difference between anti-HER2 + ChT and anti-HER2 + ET in first-line (mPFS, 15.0m [95%CI 12.1-17.9] vs 9.0m [95%CI 0.5-17.5]; HR 1.32 [0.88-1.98]; P = 0.162) and the front two lines of treatment (PFS-2, 26.0m [95%CI 23.0-29.0] vs 24.0m [95%CI 15.9-32.1]; HR 1.03 [0.64-1.64]; P = 0.919). Notably, PFS of patients with anti-HER2 + ChT maintained by anti-HER2 + ET was superior to anti-HER2 + ET (24.0m [95%CI 18.0-30.0] vs 17.0m [95%CI 9.5-24.5]; HR 0.53 [0.32-0.89]; P = 0.005) and other anti-HER2 + ChT group (24.0m vs 12.0m [95%CI 9.1-15.0]; HR 0.52 [0.36-0.76]; P < 0.001). While anti-HER2 + ChT showed superior disease control over anti-HER2 + ET, it didn't confer a survival advantage, possibly due to small sample size or retrospective design constraints. For patients deriving benefit from anti-HER2 + ChT, transitioning tomaintenance therapy with anti-HER2 + ET may represent an optional strategy.

1016P Patient (pt) characteristics, HER2 testing, and treatment (Tx) patterns in advanced HER2 (ERBB2)-mutant (HER2m) NSCLC in real-world clinical practice

Cardiac amyloid radionuclide imaging (CARI) with 99mTc-pyrophosphate (PYP) enables the noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Recent PYP shortages have necessitated substitution with 99mTc-hydroxymethylene diphosphonate (HMDP), yet direct comparative data are limited. We aimed to compare scan interpretation, ATTR-CM prevalence, and myocardial-to-blood pool discrimination between PYP and HMDP in real-world clinical practice. We retrospectively analyzed 992 consecutive patients who underwent SPECT/CT for suspected ATTR-CM at a single referral center between October 2022 and January 2025. PYP was used except during two shortage periods (December 2023 to February 2024 and October 2024 to January 2025), when HMDP was substituted. Scan interpretation and final ATTR-CM diagnoses were recorded. The myocardial-to-blood-pool radiotracer uptake ratio (3D Score) was measured as a surrogate for contrast resolution. Of 992 unique patients (median age 76, 27% female), 816 received PYP and 176 (18%) received HMDP. Baseline clinical, echocardiographic, and biomarker characteristics were similar between groups. Rates of positive scans (PYP: 26%, HMDP: 25%; P = 0.95) and final ATTR-CM diagnoses (28% vs 26%; P = 0.59) were comparable. Among patients with positive scans (n = 256), HMDP yielded significantly higher 3D Scores (2.0 [1.7-2.5] vs 1.4 [1.2-1.7], P < 0.001), suggesting enhanced myocardial-to-blood pool contrast resolution. In a large cohort with similar clinical profiles, HMDP provided equivalent diagnostic yield and superior myocardial-to-blood-pool discrimination compared to PYP. These findings support HMDP as a good alternative during PYP shortages, with potential advantages in contrast resolution.

We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes.

BackgroundStereotactic irradiation (STI) has become a standard treatment in addition to whole-brain radiation therapy for metastatic brain tumors. However, real-world clinical practice and prognostic factors associated with this approach have not been fully elucidated.MethodsWe retrospectively analyzed 362 patients (745 lesions) with brain metastases from non-small cell lung cancer (NSCLC) who underwent stereotactic radiotherapy at nine institutions between May 2016 and April 2020.ResultsThe median patient age was 70 years, and 66.9% were male. The average number of lesions was 2, showing an increasing trend from 1.8 in 2016 to 2.2 in 2020; irradiation of five or more lesions was observed in 5.8% of cases. Chemotherapy was combined in 58.0% of patients, of which 64.6% received cytotoxic chemotherapy, 23.9% received EGFR-TKIs other than osimertinib, 7.8% received osimertinib, and 3.7% received ALK-TKIs. Over time, the use of cytotoxic agents decreased, while observation increased. Post-recurrence treatments included STI (39.6%), WBRT (21.5%), TKIs (7.4%), non-TKI chemotherapy (8.1%), immunotherapy (1.7%), surgery (6.0%), and best supportive care (14.8%). The overall median survival was 42.0 months, the 5-year survival rate was 41.5%, and the 2-year local control rate was 73.8%. Favorable prognostic factors included adenocarcinoma histology, female sex, good performance status prior to treatment, and treatment at a high-volume center. The presence of EGFR or ALK mutations was a significant favorable prognostic factor both in the overall cohort (n = 362) and in a subset analysis limited to adenocarcinoma cases (n = 268) (p < 0.001 and p = 0.0093, respectively).DiscussionThe use of STI for brain metastases from lung cancer is increasing, including for patients with five or more lesions. STI was also actively employed for recurrent lesions. The presence of genetic mutations was a key prognostic factor. As personalized medicine advances, the use of osimertinib is increasing, while the use of cytotoxic chemotherapy is declining.