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Background: Pay-for-performance system (P4P) has been in operation in the Turkish healthcare sector since 2004. While the government defended that it encouraged healthcare professionals' job motivation, and improved patient satisfaction by increasing efficiency and service quality, healthcare professionals have emphasized the system's negative effects on working conditions, physicians' trustworthiness, and cost-quality outcomes. In this study, we investigated physicians' accounts of current working conditions, their status as a moral agent, and their professional attitudes in the context of P4P's perceived effects on their professional, social, private, and future lives., Methods: First, we held 3 focus groups with 19 residents and 1 specialist regarding their lived experiences under P4P and thematically analyzed the transcripts. Second, we developed a questionnaire to assess how generalizable the qualitative findings are for a broader group of physicians. The tool has three parts questioning 1) demographic information, 2) working conditions, and 3) perceived consequences and effects of P4P. 2136 physicians responded to the survey. After refining the data, we conducted the statistical analysis over 1378 responses by using Spearman's correlation coefficient, exploratory factor analysis (EFA) for categorical data, and Kruskal-Wallis variance analysis., Results: Thematic analysis revealed two dimensions: 1) factors leading to estrangement, and 2) manifestations of estrangement. As for the initial, participants thought that P4P affected relationships at work; family and social relationships; working conditions; quality of the specialty training; quality of healthcare services; and it caused healthcare system-related consequences. Concerning the latter, the following themes emerged: Estrangement of the physician; damaging effects on physician's psychology; physician's perception of their future life; and physician as a moral agent. According to EFA, a 5-factor structure was appropriate: F1) Estrangement; F2) adverse effects on the physician's quality of life; F3) favorable consequences; F4) physicians becoming disreputable; F5) unfavorable consequences., Conclusions: The findings suggest that under P4P, physicians have become more estranged towards their profession, their patients, and themselves. They suffer from deteriorating working conditions, lack of motivation, lack of work-related satisfaction, and hopelessness regarding their future. Furthermore, P4P impairs their ability to realize themselves as moral subjects practicing in alignment with professional values and principles., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ankara University Ethics Committee on 02.03.2012 in accordance with the decision number 111/445. All methods were performed in accordance with the relevant guidelines and regulations including the Declaration of Helsinki. Informed consent to participate in the study was obtained from all the FG participants. The questionnaire was delivered online. A detailed explanation of the aim of the study and the nature of the questionnaire was present at the beginning (in the first page) of the tool. Thus, those who agreed to participate in the questionnaire survey were considered that they had consented to submit their entries as they needed to click “forward” after reading the explanation. In that section, personal information was not required; the raw data were anonymized. Consent for publication: All subjects (both the FG participants and the questionnaire respondents) consented for publication of the findings based on the data they provided. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Voriconazole is a broad-spectrum antifungal agent. It is used widely for the prevention and treatment of invasive fungal infections in patients with a hematological malignancy, but studies on its safety in this population are scarce. We assessed the adverse drug events (ADEs) of voriconazole in this population based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to improve understanding of the safety of voriconazole. Research design and methods: ADE reports for patients with a hematological malignant tumor using voriconazole between the first quarter of 2004 to the first quarter of 2024 were retrieved. Then, they were classified using the preferred terminology (PT) and system organ category (SOC) in the Medical Dictionary for Regulatory Activities. Data mining was done using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Results: A total of 605 ADEs were included: 116 (19.17%) in children and 489 (80.83%) in adults. The types of SOC involved in children and adults were 22 and 24, respectively. The only positive SOC signal that satisfied all four algorithms simultaneously in children was "psychiatric disorders", whereas in adults they were "endocrine disorders" and "hepatobiliary disorders". At the PT level, the types involved in children and adults were 28 and 74, respectively. The highest ROR signal intensities were found for "hallucinations, mixed" in children and "toxic optic neuropathy" in adults. The median time of onset of the ADE in children and adults was 11 and 8.5 days, respectively. Conclusion: We used four algorithms (ROR, PRR, BCPNN, MGPS) to mine the signals of voriconazole in patients with a hematological malignant tumor, and compared the differences between children and adults. This study is important for targeting the monitoring, and could help to improve the safety of voriconazole. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim is to assess current lower extremity MRI requests' relevance with a secondary focus on the knee., Materials and Methods: Using data from the National Health Data System (SNDS), we conducted an observational study of adults (18+) who underwent lower extremity MRI between July 1 and December 31, 2021. This study included analyzing medical consultations and imaging procedures (particularly X-rays) in the 6 months before and after the index MRI, as well as medical procedures and hospitalizations related to knee procedures within 6 months post-MRI., Results: During the study period, 779,721 adults underwent lower extremity MRI, marking a 76% increase compared to a previous study conducted in 2012. General practitioners requested MRI in 70.5% of cases, often as the primary imaging modality. Notably, 52.1% of patients had not undergone lower extremity X-rays in the 6 months preceding MRI, and 13% underwent at least two MRI examinations within a year. Focusing on the knee, most patients (80%) did not undergo any outpatient medical procedure or hospitalization involving the knee within the 6 months post MRI., Conclusion: In France, lower extremity MRI, particularly knee MRI, is frequently used as a first-line imaging procedure, unlike what is recommended., Key Points: Question How often are requests for lower extremity MRI examinations appropriate? Findings Lower extremity MRI is often performed as a first-line imaging procedure, even though it is not recommended. Clinical relevance The study findings underscore the importance of disseminating guidelines regarding lower extremity MRI appropriateness to increase its availability for appropriate purposes, thereby improving patient care., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Marie Faruch-Bilfeld. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: This study was authorized by Decree 2016-1871 of December 26, 2016, on the processing of personal data in the French National Health Data System (Système National des Données de Santé [SNDS]) and Articles 1461-13 and 14 of French law. The HAS, which has permanent regulatory access to SNDS data, did not require the consent of the participants or the approval of the institutional review board. Ethical approval: This study was authorized by Decree 2016-1871 of December 26, 2016, on the processing of personal data in the French National Health Data System (Système National des Données de Santé [SNDS]) and Articles 1461-13 and 14 of French law. The HAS, which has permanent regulatory access to SNDS data, did not require the consent of the participants or the approval of the institutional review board. Study subjects or cohorts overlap: No study subjects or cohorts have been previously reported. Methodology: Retrospective Observational Multicenter study, (© 2025. The Author(s).)

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases. We identified a bone marrow progenitor (BMP)-like leukemia subpopulation associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL and revealed that NOTCH1 mutations additively drive T-ALL blasts away from the BMP-like state. Through in silico and in vitro drug screenings, we identified a therapeutic vulnerability of BMP-like blasts to apoptosis-inducing agents including venetoclax. Collectively, our study establishes multiomic signatures for rapid risk stratification and targeted treatment of high-risk T-ALL., Competing Interests: Competing interests: D.T.T. received research funding from BEAM Therapeutics and NeoImmune Tech and serves on advisory boards for BEAM Therapeutics, Janssen, Servier, Sobi and Jazz. D.T.T. has multiple patents pending on chimeric antigen receptor T cell therapy. The other authors declare no competing interests., (© 2024. The Author(s).)