Voriconazole-induced central nervous system toxicity: a pharmacovigilance study based on FDA adverse event reporting system (FAERS) database.

BACKGROUND: This study aims to evaluate the relationship between voriconazole (VRC) and central nervous system (CNS) toxicity based on the real world data. RESEARCH DESIGN AND METHODS: The reports of FAERS from January 2004 to March 2022 were included in our study. The CNS toxicity events were identified by using Medical Dictionary for Regulatory Activities terms. Reporting odds ratios corresponding to 95% confidence intervals were employed to quantify the signals of VRC-associated CNS events. RESULTS: The overall RORs (95%CI) for psychiatric disorders, nervous system disorders, and eye disorders were 1.84 (1.70, 2.00), 1.09 (1.01, 1.18), and 3.84 (3.48, 4.23), respectively (p < 0.05). The median time to the CNS events of VRC was 1(IQR 0-5) day. Top six signals were macular opacity, chloropsia, scintillating scotoma, toxic optic neuropathy, corneal bleeding, and dyschromatopsia, all of them grouped as eye disorders. Compared with itraconazole, fluconazole, posaconazole, and isavuconazole, VRC shows significant relationship and higher incidence rate of psychiatric disorders, nervous system disorders, and eye disorders, respectively (p < 0.05). CONCLUSIONS: VRC was significantly associated with the CNS toxicity. Dosing adjustment, model-based individualized treatment project, and the therapeutic drug monitoring-guided individualized medication regime could be good strategies for efficacy improvement and the adverse events of reducing of VRC.

Characteristics of eye disorders induced by atypical antipsychotics: a real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System.

Background: Common atypical antipsychotics include risperidone, paliperidone, olanzapine, lurasidone, quetiapine, clozapine, aripiprazole, ziprasidone, asenapine, brexpiprazole, and cariprazine. Previous studies on ocular adverse reactions of antipsychotics were mainly focused on typical antipsychotics. Systematic research on atypical antipsychotics remains limited. Objective: This study aimed to evaluate the potential risks of different atypical antipsychotics causing ocular side effects by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Extract reports from the FAERS from the first quarter of 2016 to the fourth quarter of 2022 were obtained. Data mining of eye disorders associated with atypical antipsychotics was carried out using The Reporting Odds Ratio (ROR) method and The Medicines and Healthcare Products Regulatory Agency (MHRA) method to determine positive signals. Results: FAERS reports for 9913783 cases were included in these 28 quarters. 64 defined ocular adverse events were classified into 10 categories according to High-Level Group Terms (HLGT). Conclusions: There were differences in the types and severity of ocular-related adverse events associated with atypical antipsychotics. Ocular neuromuscular-related adverse events were found among all 11 atypical antipsychotics. Olanzapine had the highest signal intensity in oculogyric crisis. Aripiprazole had the highest signal strength in blepharospasm. Cariprazine was associated with cataract-related ocular adverse reactions. In terms of the types of adverse events, our study found that aripiprazole was associated with 28 types of ocular adverse events, followed by quetiapine. Clozapine was only associated with two types of ocular adverse events.

Time to intravenous diuretic administration in patients hospitalized with heart failure: An observational study.

AIMS: To help establish optimized treatment strategies for congestion in patients with acute heart failure, this study aimed to provide a detailed summary of real-world diuretic use in hospitalized patients with heart failure requiring urgent therapy in Japan. METHODS AND RESULTS: This observational study used a Japanese medical records database to extract data of patients admitted to hospital with a heart failure diagnosis and an intravenous diuretic prescription from the day before admission to 2 days after. Time from hospital visit to first dose, second dose, and maximum dose of intravenous diuretics were determined. Patients were grouped according to whether they received diuretic modification, defined as an intravenous diuretic dose increase or concomitant use of other diuretics. RESULTS: Overall, 1577 patients were included in the study (without diuretic modification, n = 1140 [72.3%]; with diuretic modification, n = 437 [27.7%]). The study population was 49.5% female (n = 780) and the mean age ± standard deviation was 80.1 ± 12.7 years. Intravenous diuretic treatment was received within 1 h of their hospital visit in 43.5% of patients (686/1577) and ≤2 h in 16.4% of patients (258/1577). Among 437 patients with an inadequate response following their first dose, 42.1% received an intravenous dose titration, 56.5% received combination diuretics, and 1.4% received both. Over half of the patients (59.0% [258/437]) with diuretic modification received it after the first 24 h of the hospital visit. The median time from hospital visit to first dose titration was similar to time to first combination diuretic use (18.6 h and 17.0 h, respectively). The mean ± standard deviation duration of intravenous diuretic use was significantly longer for patients with versus without diuretic modification (6.3 ± 5.2 vs. 3.7 ± 3.2 days), and a significantly greater proportion of patients (44.6% [195/437] vs. 35.0% [399/1140]) received repeated intravenous diuretic administration. Other characteristics/outcomes of intravenous diuretic use were similar with versus without diuretic modification, including in-hospital death (15.6% [68/437] vs. 13.9% [159/1140]) and mean ± standard deviation length of hospitalization (21.9 ± 14.7 days vs. 22.1 ± 21.2 days). CONCLUSIONS: In Japan, real-world patterns of intravenous diuretic administration for patients with heart failure remains far from the time-sensitive approach recommended in Japanese, European, and United States guidelines.

Clinical Characteristics of Moxifloxacin-Related Arrhythmias and Development of a Predictive Nomogram: A Case Control Study.

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin-related arrhythmias and electrocardiographic alterations in hospitalized patients using real-world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug-induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156-1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568-9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800-7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531-3.690), and abnormally elevated level of amino-terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640-5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220-0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin-related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin-administered population, offering significant clinical applications.

Italian Patient Satisfaction with wAMD Management: SWAN Study Results.

Purpose: Limited data is available on treatment satisfaction with the management of wet age-related macular degeneration (wAMD) among patients in Italy. In this cross-sectional real-world study, treatment satisfaction with anti-vascular endothelial growth factor (anti-VEGFs) was assessed in patients with wAMD in Italy. Patients and Methods: This was a non-interventional, cross-sectional survey involving patients with wAMD receiving anti-VEGFs. The survey was administered through a virtual assistant via phone. Patients' treatment satisfaction was assessed using a newly developed Novartis Tailored Treatment Satisfaction Questionnaire (NVS TTSQ) and the validated Macular Disease Treatment Satisfaction Questionnaire (MacTSQ). Results: Overall, 154 evaluable patients were enrolled in 5 centers across Italy. The mean (SD) age of the patients was 76.8 years (7.01). Overall treatment satisfaction score assessed by NVS TTSQ was 40.50 (7.11), with a mean of 9.97 (1.84) on the information domain and 22.98 (4.57) on the unmet need domain. Patients were satisfied with diagnosis communication (4.99 [1.30]), information provided on treatment administration (4.58 [1.49], range 0-6), the waiting room (4.40 [1.43]), and management of visits and injections at the center (5.14 [1.12]), general management of maculopathy at the center (5.22 [1.01]). Patients were not satisfied with their independence in terms of disease management (2.56 [2.45]); they would like additional information about the disease (5.38 [1.03]) and to discuss the injection procedures (4.02 [1.94]) with already-treated patients. The overall treatment satisfaction score on MacTSQ scale was 55.84 (10.13). Conclusion: Patients with wAMD are satisfied with the overall management of their disease in Italy. However, patients would like to have more information on prognosis and management of the disease.

An Economic Evaluation of Family-Based Versus Traditional Helicobacter pylori Screen-and-Treat Strategy: Based on Real-World Data and Microsimulation Model.

OBJECTIVE: There is an economic evaluation on the family-based Helicobacter pylori screen-and-treat strategy (FBHS) in China. This study aimed to compare the cost-effectiveness of the FBHS with the traditional H. pylori screen-and-treat strategy (TBHS). MATERIALS AND METHODS: A seven-state microsimulation model, including H. pylori infection and gastric cancer states, was constructed on the basis of the target family samples from 29 provinces in China. Taking a lifetime horizon from a healthcare system perspective, the long-term costs and health outcomes of the FBHS and TBHS screening strategies were simulated separately, and economic evaluations were performed. The model parameters were primarily derived from real-world data, published literature, and expert opinions. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/quality-adjusted life-year (QALY) gained. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were performed to assess the uncertainty of the results. RESULTS: The base-case analysis revealed that the average costs for FBHS and TBHS were 563.67 CNY and 574.08 CNY, respectively, with corresponding average QALYs of 14.83 and 14.79. The ICER for the comparison between the two strategies was -214.07, indicating that FBHS was an absolutely dominant strategy with better cost-effectiveness. The results of both one-way sensitivity analysis and probabilistic sensitivity analysis were robust. When taking into account the added benefit of the higher H. pylori eradication rate in FBHS, the average costs were further reduced, and the average QALYs were increased, solidifying its position as an unequivocally dominant strategy. CONCLUSION: The FBHS is an absolutely dominant and cost-effective strategy that enables an optimized allocation of screening resources. Decision-makers should prioritize FBHS when developing H. pylori prevention and control strategies.

Real-world effectiveness and safety of Baloxavir Marboxil or Oseltamivir in outpatients with uncomplicated influenza A: an ambispective, observational, multi-center study.

Introduction: Baloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce. Methods: We conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza. Results: A total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0 h (IQR, 20.0 to 50.0) and 48.0 h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18 h (IQR, 10.0-24.0) and 30.0 h (IQR, 19.0-48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR = 1.36 [95%CI:1.12-1.64], p = 0.002) and the duration of fever (HR = 1.93 [95%CI:1.48-2.52], p < 0.001) compared to Oseltamivir. When antiviral drugs were given within 12-48 h after symptom onset, the Baloxavir Marboxil group had a significantly shorter TTAIS compared to the Oseltamivir group. There was no significant difference in the rate of adverse events between the two group (p = 0.555). Discussion: Baloxavir Marboxil was superior to Oseltamivir in alleviating influenza symptoms in outpatients with uncomplicated influenza. Our findings suggested that compared to Oseltamivir, Baloxavir Marboxil might be more appropriate for patients with influenza 12- 48 h after symptom onset.

A two-stage maintenance trial of cetuximab-based treatment in RAS and BRAF wild-type unresectable metastatic colorectal cancer: a retrospective real-world study.

Background: To investigate the effectiveness and safety of maintenance regimens based on cetuximab, we conducted a real-world, single-arm, retrospective study at a single center. Methods: In Fujian Medical University Union Hospital, patients with unresectable metastatic colorectal cancer (mCRC) who received cetuximab-based maintenance therapy between December 2020 and December 2021 were included. All patients had RAS and BRAF wild-type. The maintenance regimen consisted of 6-12 cycles of cetuximab plus irinotecan (Phase 1) and cetuximab (Phase 2). Patients could receive reintroduction therapy in case of disease progression during Phase 2. Progression-free survival (PFS), overall survival (OS), and safety data were collected. Results: According to the inclusion and exclusion criteria of the study, a total of 108 subjects who received maintenance therapy were included- 51 experienced disease progression during Phase 1, with PFS (1) of 7.3 months. Among the 52 patients who entered Phase 2, 17 were still in this phase at the end of follow-up, with PFS (2) of 10.1 months. In Phase 2, 35 patients experienced disease progression, of whom 24 received reintroduction therapy, with PFS (3) of 6.7 months. The overall PFS (total) during the maintenance period was 11.9 months, and the OS was 39.2 months. Grade III or higher adverse events were 4.6% during Phase 1 and 0% during Phase 2. Conclusion: Innovative cetuximab-based maintenance therapy showed a trend toward improving the prognosis of mCRC patients with RAS and BRAF wild-type, while the toxic side effects of maintenance therapy were manageable. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2000040940.

Maintenance therapy for cytogenetically high-risk multiple myeloma: landscape in the era of novel drugs.

Although the significant strides in novel therapeutic approaches have prolonged the survival of multiple myeloma (MM) patients, the unfavorable prognosis of cytogenetically high-risk newly diagnosed MM (NDMM) remains intractable with the lack of consensus regarding the choice of maintenance regimens. Therefore, this study was initiated with the aim of examining the effectiveness of various maintenance treatments for this group of patients in jeopardy. Overall, 17 studies with 1937 high-risk NDMM patients were included in the network meta-analysis. Combination therapies involving novel drugs presented encouraging prospects in the maintenance phase, while the patients and circumstances for the application of different regimens still needed to be further distinguished and clarified. To investigate the current status of maintenance therapy of high-risk NDMM patients in clinical practice, a real-world cohort of high-risk NDMM was retrospectively incorporated 80 patients with lenalidomide maintenance and 53 patients with bortezomib maintenance, presenting the median PFS of 31.7 months and 30.4 months, respectively (p = 0.874, HR = 0.966, 95% CI: 0.628-1.486). Collectively, this study illuminated the present constraints of conventional approaches during the maintenance phase for high-risk NDMM patients while highlighting the future potential associated with enhanced regimens integrating novel medications.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

Pediatric-onset Multiple Sclerosis treatment: a multicentre observational study comparing natalizumab with fingolimod.

BACKGROUND: Pediatric-onset Multiple Sclerosis (POMS) patients show more inflammatory disease compared with adult-onset MS. However, highly effective treatments are limited with only fingolimod being approved in Italy and natalizumab prescribed as off-label treatment. OBJECTIVES: to compare the efficacy of natalizumab versus fingolimod in POMS. METHODS: This is an observational longitudinal multicentre study including natalizumab- and fingolimod-treated POMS patients (N-POMS and F-POMS, respectively). We collected Annual Relapse Rate (ARR), Expanded Disability Status Scale (EDSS), Symbol Digit Modality Test (SDMT), and MRI activity at baseline (T0), 12-18 months (T1), and last available observation (T2). RESULTS: We enrolled 57 N-POMS and 27 F-POMS patients from six Italian MS Centres. At T0, N-POMS patients showed higher ARR (p = 0.03), higher EDSS (p = 0.003) and lower SDMT (p = 0.04) at baseline compared with F-POMS. Between T0 and T1 ARR improved for both N-POMS and F-POMS (p < 0.001), while EDSS (p < 0.001) and SDMT (p = 0.03) improved only for N-POMS. At T2 (66.1 ± 55.4 months) we collected data from 42 out of 57 N-POMS patients showing no further ARR decrease. CONCLUSION: Both natalizumab and fingolimod showed high and sustained efficacy in controlling relapses and natalizumab also associated to a disability decrease in POMS. This latter effect might be partly mediated by the high inflammatory activity at baseline in N-POMS.

Jin-Gu-Lian Capsule Did Not Significantly Improve Clinical Value in Rheumatoid Arthritis Therapy: A Real-World Study.

Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS). Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect. Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL. Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.

Comparative Effectiveness of Dupilumab and Omalizumab on Asthma Exacerbations and Systemic Corticosteroid Prescriptions: Real-World US ADVANTAGE Study.

BACKGROUND: In the US, dupilumab is approved for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, while omalizumab is approved for managing moderate-to-severe allergic asthma uncontrolled by inhaled corticosteroids. However, limited comparative effectiveness data exist for these biologics due to differing patient characteristics and treatment histories. OBJECTIVE: This analysis assessed the real-world effectiveness of dupilumab and omalizumab for asthma among patients in the US. METHODS: In this retrospective observational study, TriNetX Dataworks electronic medical record data were used to identify asthma patients (age: ≥12 years) who initiated (index) dupilumab or omalizumab between November 2018 and September 2020, and who had at least 12 months of pre- and post-index clinical information. Inverse probability of treatment weighting (IPTW) was applied to balance potential confounding in treatment groups. Asthma exacerbation rates and systemic corticosteroid (SCS) prescriptions were compared using a doubly robust negative binomial regression model, adjusting for baseline exacerbation/SCS rates and patient characteristics with ≥10% standardized differences after IPTW. RESULTS: Overall, 2,138 patients in dupilumab and 1,313 in omalizumab treatment groups met all inclusion and exclusion criteria. After weighting, the majority of baseline characteristics were balanced (standard difference <10%) between the two groups. Dupilumab was associated with a 44% lower asthma exacerbation rate (p<0.0001) than omalizumab. Additionally, dupilumab treatment significantly (p<0.05) reduced SCS prescriptions by 28% during the follow-up period compared to omalizumab treatment. CONCLUSION: The US ADVANTAGE real-world study demonstrated a significant reduction in severe asthma exacerbations and SCS prescriptions for patients prescribed dupilumab compared to those prescribed omalizumab during 12 months of follow-up.

Clinical management of children with tic disorder: insights from therapeutic visits in China-a real-world study.

Objective: This retrospective study aims to investigate the treatment of tic disorder (TD) in Dongfang Hospital affiliated with Beijing University of Chinese Medicine, explore its underlying mechanism, and provide valuable insights for future research and clinical management of TD. Methods: The electronic medical records of children with TD, from 2015 to 2021, were extracted from the information system of Dongfang Hospital affiliated with Beijing University of Chinese Medicine. The clinical characteristics of TD, utilization patterns of Chinese herbal medicine and synthetic drugs in prescriptions, as well as their pharmacological effects, were statistically described and categorized. In addition, association rules and network pharmacology were employed to identify core prescriptions (CPs) and elucidate their microscopic molecular mechanisms in treating TD. Results: The age range of the children was from 6 to 11 years, with a higher proportion of male participants than female ones. The average duration of treatment was 6 weeks. Regimen Z for the treatment of TD can be summarized as follows: Chinese herbal medicine [Saposhnikoviae Radix (FangFeng), Puerariae Lobatae Radix (GeGen), Uncariae Ramulus cum Uncis (GouTeng), Acori Tatarinowii Rhizoma (ShiChangPu), Chuanxiong Rhizoma (ChuanXiong)] and vitamins [lysine, inosite, and vitamin B12 oral solution] form the basic treatment, combined with immunomodulators, antibiotics, electrolyte-balancing agents, and antiallergic agents. CPs primarily exerted their effects through the modulation of gene expression (transcription), the immune system, and signal transduction pathways, with interleukin-4 and interleukin-13 pathways being particularly crucial. Among the lysine synthetic drugs used, inosite and vitamin B12 oral solution were the most frequently prescribed. Conclusion: The regimen Z drug treatment holds significant importance in the field, as it exerts its therapeutic effects through a multitude of pathways and intricate interventions. Chinese herbal medicine primarily regulates immune system-related pathways, while synthetic drugs predominantly consist of vitamins.

Ulinastatin shortens the length of ICU stay in critical patients with organ failure: A 7-year real-world study.

BACKGROUND: Ulinastatin has been applied in a series of diseases associated with inflammation but its clinical effects remain somewhat elusive. OBJECTIVE: We aimed to investigate the potential effects of ulinastatin on organ failure patients admitted to the intensive care unit (ICU). METHODS: This is a single-center retrospective study on organ failure patients from 2013 to 2019. Patients were divided into two groups according to using ulinastatin or not during hospitalization. Propensity score matching was applied to reduce bias. The outcomes of interest were 28-day all-cause mortality, length of ICU stay, and mechanical ventilation duration. RESULTS: Of the 841 patients who fulfilled the entry criteria, 247 received ulinastatin. A propensity-matched cohort of 608 patients was created. No significant differences in 28-day mortality between the two groups. Sequential organ failure assessment (SOFA) was identified as the independent risk factor associated with mortality. In the subgroup with SOFA ≤ 10, patients received ulinastatin experienced significantly shorter time in ICU (10.0 d [interquartile range, IQR: 7.0∼20.0] vs 15.0 d [IQR: 7.0∼25.0]; p = .004) and on mechanical ventilation (222 h [IQR:114∼349] vs 251 h [IQR: 123∼499]; P = .01), but the 28-day mortality revealed no obvious difference (10.5% vs 9.4%; p = .74). CONCLUSION: Ulinastatin was beneficial in treating patients in ICU with organ failure, mainly by reducing the length of ICU stay and duration of mechanical ventilation.

Safety of Antiplatelet Therapy in Noncardioembolic Ischemic Stroke With Thrombocytopenia: The CASE II Study.

BACKGROUND: There is scant evidence regarding the safety of antiplatelet therapy in acute ischemic stroke (AIS) patients with thrombocytopenia. Our study aims to address this concern by examining AIS patients with thrombocytopenia from a large database in real-world settings. METHODS AND RESULTS: We included patients with AIS with a platelet count <100×109/L who had complete records of antiplatelet drug use. Those requiring anticoagulation or having contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was 1-year all-cause mortality. A good clinical outcome was defined as functional independence, indicated by a modified Rankin Scale score of 0 to 2 at discharge. Propensity score matched analyses were used. We screened 169 423 patients with AIS from 90 stroke centers in the CASE II register, ultimately enrolling 2808 noncardioembolic patients with thrombocytopenia. In the propensity score matched analyses, no significant difference was observed between the antiplatelet and nonantiplatelet groups in terms of intracranial hemorrhage (odds ratio=0.855 [95% CI, 0.284-5.478]; P=0.160) or gastrointestinal bleeding (odds ratio=2.034 [95% CI, 0.755-5.478]; P=0.160). Antiplatelet therapy was associated with improved functional outcomes at discharge (odds ratio=1.405 [95% CI, 1.028-1.920]; P=0.033), and showed a trend towards reducing 1-year mortality (odds ratio=0.395 [95% CI, 0.152-1.031]; P=0.058). CONCLUSIONS: The use of antiplatelet therapy lessened as platelet count decreased in patients with AIS with thrombocytopenia. However, our findings suggest that antiplatelet medications remain safe and effective for this population.

Cost analysis of radical resection of malignant breast tumors under the China Healthcare Security Diagnosis Related Groups payment system.

BACKGROUND: Breast cancer is one of the most common malignant tumors in women worldwide and poses a severe threat to their health. Therefore, this study examined patients who underwent breast cancer surgery, analyzed hospitalization costs and structure, and explored the impact of China Healthcare Security Diagnosis Related Groups (CHS-DRG) management on patient costs. It aimed to provide medical institutions with ways to reduce costs, optimize cost structures, reduce patient burden, and improve service efficiency. AIM: To study the CHS-DRG payment system's impact on breast cancer surgery costs. METHODS: Using the CHS-DRG (version 1.1) grouping criteria, 4073 patients, who underwent the radical resection of breast malignant tumors from January to December 2023, were included in the JA29 group; 1028 patients were part of the CHS-DRG payment system, unlike the rest. Through an independent sample t-test, the length of hospital stay as well as total hospitalization, medicine and consumables, medical, nursing, medical technology, and management expenses were compared. Pearson's correlation coefficient was used to test the cost correlation. RESULTS: In terms of hospitalization expenses, patients in the CHS-DRG payment group had lower medical, nursing, and management expenses than those in the diagnosis-related group (DRG) non-payment group. For patients in the DRG payment group, the factors affecting the total hospitalization cost, in descending order of relevance, were medicine and consumable costs, consumable costs, medicine costs, medical costs, medical technology costs, management costs, nursing costs, and length of hospital stay. For patients in the DRG non-payment group, the factors affecting the total hospitalization expenses in descending order of relevance were medicines and consumable expenses, consumable expenses, medical technology expenses, the cost of medicines, medical expenses, nursing expenses, length of hospital stay, and management expenses. CONCLUSION: The CHS-DRG system can help control and reduce unnecessary medical expenses by controlling medicine costs, medical consumable costs, and the length of hospital stay while ensuring medical safety.

Clinical characteristics and COVID-19-related outcomes of immunocompromised patients receiving tixagevimab/cilgavimab pre-exposure prophylaxis in Japan.

OBJECTIVE: Tixagevimab/cilgavimab is a cocktail of two long-acting monoclonal antibodies approved for pre-exposure prophylaxis (PrEP) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (cause of coronavirus disease 2019 [COVID-19]) in immunocompromised (IC) or high-risk patients. We investigated the patient characteristics and clinical outcomes of IC patients administered tixagevimab/cilgavimab for PrEP in real-world use in Japan. METHODS: This observational study used anonymous secondary data from Real-World Data Co., Ltd. for IC patients aged ≥12 years administered tixagevimab/cilgavimab between September 2022 and September 2023. We analyzed the baseline characteristics and event-rates of COVID-19-related clinical outcomes within 6 months of administration. RESULTS: Data were analyzed for 397 IC patients. About half (53.4 %) were male and the median age was 71.0 (interquartile range 61.0, 77.0) years. Malignancy (97.2 %), cardiovascular disease (71.3 %), and diabetes (66.5 %) were frequent comorbidities. Systemic corticosteroids and immunosuppressants were prescribed to 87.4 % and 24.9 %, respectively. The two most common target clinical conditions were active therapy for hematologic malignancies (88.2 %) and treatment with B cell-depleting therapies (57.4 %). The event-rates per 100 person-months (95 % confidence interval; number) for medically attended COVID-19, COVID-19 hospitalization, in-hospital mortality due to COVID-19, and all-cause death were 4.14 (3.06-5.48; n = 49), 1.74 (1.09-2.64; n = 22), 0.07 (0.00-0.42; n = 1), and 0.60 (0.26-1.17; n = 8), respectively. CONCLUSION: This is the first report using a multicenter database to describe the clinical characteristics and COVID-19-related outcomes of IC patients administered with tixagevimab/cilgavimab in real-world settings in Japan. This cohort of IC patients who received tixagevimab/cilgavimab included many elderly patients with comorbidities.

Real-World Treatment Patterns and Outcomes of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma Treated in US Oncology Practices.

Background: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US. Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018-2021). A clinical trial-like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan-Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort. Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6-9.0) months and 16.4 (13.3-21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8-29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age <60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status <3-4 (HR range, 0.13-0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without. Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.