Применение метода аналитических сетей для оптимизации процесса выбора стратегии развития пассажирского автотранспортного предприятия

В статье обозначена проблема снижения рентабельности пассажирских автотранспортных предприятий и связанные с этим сложности по реализации процедуры стратегического прогнозирования и управления предприятием. Обосновано использование метода аналитических сетей в модели поддержки принятия решений при управлении стратегией автотранспортного предприятия, представленной в работе [1], в качестве инструмента, позволяющего формализовать экспертные знания на основных этапах оценки и выбора проектов стратегического развития. Описаны основные шаги и приведены результаты расчета алгоритма метода аналитических сетей в рамках данной модели.The article outlines the problem of reducing the profitability of passenger motor transport enterprises and the associated difficulties in implementing the procedure of strategic forecasting and enterprise management. The use of the method of analytical networks in the model of decision support in managing the strategy of a trucking enterprise presented in [1] is substantiated as a tool that allows to formalize expert knowledge at the main stages of evaluation and selection of projects for strategic development. The main steps and calculations of the algorithm algorithm for analytical networks within the framework of this model are described

Feasibility of azacitidine added to standard chemotherapy in older patients with acute myeloid leukemia - a randomised SAL pilot study

INTRODUCTION: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML. TRIAL DESIGN: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size. PATIENTS AND METHODS: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint. RESULTS: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days. CONCLUSIONS: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm

Cardiorespiratory Fitness and Insulin Sensitivity in Overweight or Obese Subjects May Be Linked Through Intrahepatic Lipid Content

Objective: Low cardiorespiratory fitness predisposes to cardiovascular disease and type 2 diabetes mellitus in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. Research Design and Methods: We included 138 overweight to obese, otherwise healthy subjects (age: 43.6 +/- 8.9 yrs., body mass index: 33.8 +/- 4 kg/m(2)). Body composition was estimated by bio-impedance analyses. Abdominal fat distribution, intramyocellular, and intrahepatic lipid content were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate individual's cardiorespiratory fitness. Insulin sensitivity was determined during an oral glucose tolerance test. Results: For all subjects, cardiorespiratory fitness was related to insulin sensitivity (r=0.32, p<0.05), IHL (r=-0.27, p<0.05), visceral (r=-0.25, p<0.05) and total fat mass (r=-0.32, p<0.05), but not to intramyocellular lipids (r=-0.08, ns). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat and fitness (r(2)=-0.43, p<0.01; r(2)=-0.34 and r(2)=0.29, p<0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r=0.16, ns), whereas it remained significant when adjusted for visceral- or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. Conclusions: Our study suggests that the positive effect of increased cardiorespiratory fitness in overweight to obese subjects on insulin sensitivity may be mediated indirectly through IHL reduction

A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia

Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62–86] years) were enrolled. One patient did not receive study medication and was replaced. Nine (69%) patients had relapsed or refractory disease and 6 (46%) patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41

Feasibility of Azacitidine Added to Standard Chemotherapy in Older Patients with Acute Myeloid Leukemia — A Randomised SAL Pilot Study

Introduction: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML. Trial Design: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size. Patients and Methods: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of ,20,000/ml at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint. Results: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days. Conclusions: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm. Trial Registration: This trial is registered at clinical trials.gov (identifier: NCT00915252)