Novel bleeding risk score for patients with atrial fibrillation on oral anticoagulants, including direct oral anticoagulants

Objective: Balancing bleeding risk and stroke risk in patients with atrial fibrillation (AF) is a common challenge. Though several bleeding risk scores exist, most have not included patients on direct oral anticoagulants (DOACs). We aimed at developing a novel bleeding risk score for patients with AF on oral anticoagulants (OAC) including both vitamin K antagonists (VKA) and DOACs. Methods: We included patients with AF on OACs from a prospective multicenter cohort study in Switzerland (SWISS-AF). The outcome was time to first bleeding. Bleeding events were defined as major or clinically relevant non-major bleeding. We used backward elimination to identify bleeding risk variables. We derived the score using a point score system based on the β-coefficients from the multivariable model. We used the Brier score for model calibration (<0.25 indicating good calibration), and Harrel's c-statistics for model discrimination. Results: We included 2147 patients with AF on OAC (72.5% male, mean age 73.4 ± 8.2 years), of whom 1209 (56.3%) took DOACs. After a follow-up of 4.4 years, a total of 255 (11.9%) bleeding events occurred. After backward elimination, age > 75 years, history of cancer, prior major hemorrhage, and arterial hypertension remained in the final prediction model. The Brier score was 0.23 (95% confidence interval [CI] 0.19–0.27), the c-statistic at 12 months was 0.71 (95% CI 0.63–0.80). Conclusion: In this prospective cohort study of AF patients and predominantly DOAC users, we successfully derived a bleeding risk prediction model with good calibration and discrimination

High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice.

Purpose. Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximab- and panitumumab-based treatments in metastatic colorectal cancer (CRC) patients. Nevertheless, most experiences were conducted on samples from primaries. The aim of this study was to evaluate the grade of concordance in terms of KRAS status between primaries and related metastases. Patients and Methods. We analyzed KRAS codon 12 and 13 mutations from formalin-fixed sections of 107 CRC primaries and related metastases. Eight pairs were excluded from the analysis because of the low amount of tumor tissue in the available samples. The main characteristics were: 50 men, 49 women; median age at diagnosis, 71 years (range, 41-84). The metastatic sites analyzed were the liver in 80 patients (80.8%), lung in seven patients (7.1%), and other sites in 12 patients (12.1%). Results. A KRAS mutation was found in 38 (38.4%) primary tumors and in 36 (36.4%) related metastases. The rate of concordance was 96.0% (95% confidence interval, 90.0%-98.9%). Discordance was observed in only four (4%) patients. Conclusions. Our results indicate that the detection of KRAS mutations in either primary or metastatic tumors from patients with CRC is concordant and this assessment could be used to predict response to targeted therapies such as cetuximab and panitumumab

Equilibrium and dynamical properties of two dimensional self-gravitating systems

A system of N classical particles in a 2D periodic cell interacting via long-range attractive potential is studied. For low energy density $U$ a collapsed phase is identified, while in the high energy limit the particles are homogeneously distributed. A phase transition from the collapsed to the homogeneous state occurs at critical energy U_c. A theoretical analysis within the canonical ensemble identifies such a transition as first order. But microcanonical simulations reveal a negative specific heat regime near $U_c$. The dynamical behaviour of the system is affected by this transition : below U_c anomalous diffusion is observed, while for U > U_c the motion of the particles is almost ballistic. In the collapsed phase, finite $N$-effects act like a noise source of variance O(1/N), that restores normal diffusion on a time scale diverging with N. As a consequence, the asymptotic diffusion coefficient will also diverge algebraically with N and superdiffusion will be observable at any time in the limit N \to \infty. A Lyapunov analysis reveals that for U > U_c the maximal exponent \lambda decreases proportionally to N^{-1/3} and vanishes in the mean-field limit. For sufficiently small energy, in spite of a clear non ergodicity of the system, a common scaling law \lambda \propto U^{1/2} is observed for any initial conditions.Comment: 17 pages, Revtex - 15 PS Figs - Subimitted to Physical Review E - Two column version with included figures : less paper waste

Health-related quality of life in patients with primary open-angle glaucoma. An italian multicentre observational study

PurposeAs a progressive condition, glaucoma may impair health-related quality of life (HRQoL), due to vision loss and other factors. This study evaluated HRQoL in a cohort of patients treated for primary open-angle glaucoma (POAG) and assessed its association with clinical features. MethodsThis was an Italian, multicentre, cross-sectional, observational study with the subgroup of newly diagnosed patients with POAG prospectively followed up for one year. Patients with previous or new diagnosis (or strong clinical suspicion) of POAG aged >18years were considered eligible. Information was collected on demographic characteristics, medical history, clinical presentation and POAG treatments. HRQoL was measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and Glaucoma Symptom Scale (GSS). Subscale and total scores were obtained and a Pearson correlation coefficient between instruments' scores calculated. ResultsA total of 3227 patients were enrolled from 2012 to 2013 and 3169 were analysed. Mean age was 66.9years. A total of 93.8% had a previous diagnosis (median duration: 8.0years). Median values for mean deviation and pattern standard deviation were 3.9 and 3.6 dB, respectively. Mean scores on most subscales of the NEI-VFQ-25 exceeded 75.0 and mean GSS subscale scores ranged between 70.8 and 79.7 (with a total mean score of 74.8). HRQoL scores on both scales were significantly inversely associated with POAG severity. ConclusionIn this large sample of Italians treated for POAG, disease severity was limited and HRQoL scores were high. QoL decreased with advancing disease severity. These findings confirm the role of vision loss in impairing QoL in POAG, underlying the importance of timely detection and appropriate treatment

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer

Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group.

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives. Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance. Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors. Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research.</p