Comparison of predictor approaches for longitudinal binary outcomes: application to anesthesiology data

Longitudinal data with binary repeated responses are now widespread among clinical studies and standard statistical analysis methods have become inadequate in the answering of clinical hypotheses. Instead of such conventional approaches, statisticians have started proposing better techniques, such as the Generalized Estimating Equations (GEE) approach and Generalized Linear Mixed Models (GLMM) technique. In this research, we undertook a comparative study of modeling binary repeated responses using an anesthesiology dataset which has 375 patient data with clinical variables. We modeled the relationship between hypotension and age, gender, surgical department, positions of patients during surgery, diastolic blood pressure, pulse, electrocardiography and doses of Marcain-heavy, chirocaine, fentanyl, and midazolam. Moreover, parameter estimates between the GEE and the GLMM were compared. The parameter estimates, except time-after, Marcain-Heavy, and Fentanyl from the GLMM, are larger than those from GEE. The standard errors from the GLMM are larger than those from GEE. GLMM appears to be more suitable approach than the GEE approach for the analysis hypotension during spinal anesthesia

Deciphering the Chronology of Copy Number Alterations in Multiple Myeloma (MM): What Comes First?

International audienc

Deciphering the chronology of copy number alterations in Multiple Myeloma

Abstract Multiple myeloma (MM) and its precursor condition MGUS are characterized by chromosomal aberrations. Here, we comprehensively characterize the order of occurrence of these complex genomic events underlying MM development using 500 MGUS, and MM samples. We identify hyperdiploid MM (HMM) and non-HMM as genomically distinct entities with different evolution of the copy number alterations. In HMM, gains of 9,15 or 19 are the first and clonal events observed as clonal even at MGUS stage. These events are thus early and may underlie initial transformation of normal plasma cells to MGUS cells. However, CNAs may not be adequate for progression to MM except in 15% of the patients in whom the complex subclonal deletion events are observed in MM but not MGUS. In NHMM, besides the driver translocations, clonal deletion of 13 and 1q gain are early events also observed in MGUS. We combined this information to propose a timeline for copy number alteration

Genome-Wide Somatic Alterations in Multiple Myeloma Reveal a Superior Outcome Group

International audiencePURPOSE Multiple myeloma (MM) is accompanied by heterogeneous somatic alterations. The overall goal of this study was to describe the genomic landscape of myeloma using deep whole-genome sequencing (WGS) and develop a model that identifies patients with long survival. METHODS We analyzed deep WGS data from 183 newly diagnosed patients with MM treated with lenalidomide, bortezomib, and dexamethasone (RVD) alone or RVD 1 autologous stem cell transplant (ASCT) in the IFM/DFCI 2009 study (ClinicalTrials.gov identifier: NCT01191060). We integrated genomic markers with clinical data. RESULTS We report significant variability in mutational load and processes within MM subgroups. The timeline of observed activation of mutational processes provides the basis for 2 distinct models of acquisition of mutational changes detected at the time of diagnosis of myeloma. Virtually all MM subgroups have activated DNA repair-associated signature as a prominent late mutational process, whereas APOBEC signature targeting C.G is activated in the intermediate phase of disease progression in high-risk MM. Importantly, we identify a genomically defined MM subgroup (17% of newly diagnosed patients) with low DNA damage (low genomic scar score with chromosome 9 gain) and a superior outcome (100% overall survival at 69 months), which was validated in a large independent cohort. This subgroup allowed us to distinguish patients with low-and high-risk hyperdiploid MM and identify patients with prolongation of progression-free survival. Genomic characteristics of this subgroup included lower mutational load with significant contribution from age-related mutations as well as frequent NRAS mutation. Surprisingly, their overall survival was independent of International Staging System and minimal residual disease status. CONCLUSION This is a comprehensive study identifying genomic markers of a good-risk group with prolonged survival. Identification of this patient subgroup will affect future therapeutic algorithms and research planning

Antibiotic treatment outcomes in community-acquired pneumonia

WOS: 000441766000006PubMed ID: 30119147Background/aim: The optimal empiric antibiotic regimen for patients with community-acquired pneumonia (CAP) remains unclear. This study aimed to evaluate the clinical cure rate, mortality, and length of stay among patients hospitalized with community-acquired pneumonia in nonintensive care unit (ICU) wards and treated with a beta-lactam, beta-lactam and macrolide combination, or a fluoroquinolone. Materials and methods: This prospective cohort study was perfbrined using standardized web-based database sheets from January 2009 to September 2013 in nine tertiary care hospitals in Turkey. Results: Six hundred and twenty-one consecutive patients were enrolled. A pathogen was identified in 78 (12.6%) patients. The most frequently isolated bacteria were S. pneumoniae (21.8%) and P. aeruginosa (19.2%). The clinical cure rate and length of stay were not different among patients treated with beta-lactam, beta-lactam and macrolide combination, and fluoroquinolone. Forty-seven patients (9.2%) died during the hospitalization period. There was no difference in survival among the three treatment groups. Conclusion: In patients admitted to non-ICU hospital wards for CAP, there was no difference in clinical outcomes between beta-lactam, beta-lactam and macrolide combination, and fluoroquinolone regimens.Turk Toraks DernegiThis study was supported by a grant from the Turk Toraks Dernegi. We thank the TURCAP Study Group (Kokturk N, Filiz A, Edis EC, Uzaslan E, Yalcinsoy M, Gunduz C, Dikensoy O, Cetinkaya C, Durmaz F) for their valuable contributions

ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma

Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage. The intimate link between 1q21-amplified ILF2 and the regulation of RNA splicing of DNA repair genes may be exploited to optimize the use of DNA-damaging agents in patients with high-risk MM

Community-acquired pneumonia in patients with chronic obstructive pulmonary disease requiring admission to the intensive care unit: Risk factors for mortality

Conclusion: Noninvasive ventilation, hypertension, systemic corticosteroid treatment, and shorter ICU stay are associated with reduced mortality, whereas bilateral infiltration and longer duration of invasive mechanical ventilation are associated with increased risk of mortality in patients with COPD and CAP requiring ICU admission. (C) 2013 Elsevier Inc. All rights reserved

Mortality indicators in community-acquired pneumonia requiring intensive care in Turkey

Background: Severe community-acquired pneumonia (SCAP) is a fatal disease. This study was conducted to describe an outcome analysis of the intensive care units (ICUs) of Turkey

Mortality Indicators In Community-Acquired Pneumonia Requiring Intensive Care In Turkey

Background: Severe community-acquired pneumonia (SCAP) is a fatal disease. This study was conducted to describe an outcome analysis of the intensive care units (ICUs) of Turkey. Methods: This study evaluated SCAP cases hospitalized in the ICUs of 19 different hospitals between October 2008 and January 2011. The cases of 413 patients admitted to the ICUs were retrospectively analyzed. Results: Overall 413 patients were included in the study and 129 (31.2%) died. It was found that bilateral pulmonary involvement (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.1-5.7) and CAP PIRO score (OR 2, 95% CI 1.3-2.9) were independent risk factors for a higher in-ICU mortality, while arterial hypertension (OR 0.3, 95% CI 0.1-0.9) and the application of non-invasive ventilation (OR 0.2, 95% CI 0.1-0.5) decreased mortality. No culture of any kind was obtained for 90 (22%) patients during the entire course of the hospitalization. Blood, bronchoalveolar lavage, and non-bronchoscopic lavage cultures yielded enteric Gram-negatives (n = 12), followed by Staphylococcus aureus (n = 10), pneumococci (n = 6), and Pseudomonas aeruginosa (n = 6). For 22% of the patients, none of the culture methods were applied. Conclusions: SCAP requiring ICU admission is associated with considerable mortality for ICU patients. Increased awareness appears essential for the microbiological diagnosis of this disease. (C) 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.WoSScopu