Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients.

INTRODUCTION: In a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity. METHODS: We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10(-5) digit with no replacement). RESULTS: A total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality. CONCLUSION: In a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01002482 . Registered 26 October 2009.

Tight computerized versus conventional glucose control in the ICU: a randomized controlled trial.

PURPOSE: The blood glucose target range and optimal method to reach this range remain a matter of debate in the intensive care unit (ICU). A computer decision support system (CDSS) might improve the outcome of ICU patients through facilitation of a tighter blood glucose control. METHODS: We conducted a multi-center randomized trial in 34 French ICU. Adult patients expected to require treatment in the ICU for at least 3 days were randomly assigned without blinding to undergo tight computerized glucose control with the CDSS (TGC) or conventional glucose control (CGC), with blood glucose targets of 4.4-6.1 and <10.0 mmol/L, respectively. The primary outcome was all-cause death within 90 days after ICU admission. RESULTS: Of the 2,684 patients who underwent randomization to the TGC and CGC treatment groups, primary outcome was available for 1,335 and 1,311 patients, respectively. The baseline characteristics of these treatment groups were similar in terms of age (61 ± 16 years), SAPS II (51 ± 19), percentage of surgical admissions (40.0%) and proportion of diabetic patients (20.3%). A total of 431 (32.3%) patients in the TGC group and 447 (34.1%) in the CGC group had died by day 90 (odds ratio for death in the TGC 0.92; 95% confidence interval 0.78-1.78; p = 0.32). Severe hypoglycemia (<2.2 mmol/L) occurred in 174 of 1,317 patients (13.2%) in the TGC group and 79 of 1,284 patients (6.2%) in the CGC group (p < 0.001). CONCLUSIONS: Tight computerized glucose control with the CDSS did not significantly change 90-day mortality and was associated with more frequent severe hypoglycemia episodes in comparison with conventional glucose control.

Arterial blood pressure analysis based on scattering transform I.

This article presents a new method for analyzing arterial blood pressure waves. The technique is based on the scattering transform and consists in solving the spectral problem associated to a one-dimensional Schrödinger operator with a potential depending linearly upon the pressure. This potential is then expressed with the discrete spectrum which includes negative eigenvalues and corresponds to the interacting components of an N-soliton. The approach is analogous to the Fourier transform where the solitons play the role of sinus and cosinus components. The proposed method seems to have interesting clinical applications. It can be used for example to separate the fast and slow parts of the blood pressure that correspond to the systolic (pulse transit time) and diastolic phases (low velocity flow) respectively.

Arterial blood pressure analysis based on scattering transform II.

"Arterial blood pressure analysis based on scattering transform I" introduces a new method based on the scattering transform for a one dimensional Schrödinger equation to reconstruct the arterial blood pressure waves and separate its systolic and diastolic parts. In this article, we propose to analyse the parameters computed from this technique in different clinical and physiological conditions. Two cases are considered: moderate chronic heart failure and high fit triathletes. The variability of these new parameters is compared to the variability of classical blood pressure parameters. Promising results are obtained.

An algorithm for robust and efficient location of T-wave ends in electrocardiograms.

The purpose of this paper is to propose a new algorithm for T-wave end location in electrocardiograms, mainly through the computation of an indicator related to the area covered by the T-wave curve. Based on simple assumptions, essentially on the concavity of the T-wave form, it is formally proved that the maximum of the computed indicator inside each cardiac cycle coincides with the T-wave end. Moreover, the algorithm is robust to acquisition noise, to wave form morphological variations and to baseline wander. It is also computationally very simple: the main computation can be implemented as a simple finite impulse response filter. When evaluated with the PhysioNet QT database in terms of the mean and the standard deviation of the T-wave end location errors, the proposed algorithm outperforms the other algorithms evaluated with the same database, according to the most recent available publications up to our knowledge.

A reduced differential model of the electrical activity of cardiac Purkinje fibres.

A reduced order differential model of cardiac Purkinje fibres action potential, with only eight state variables, is presented. Its structure, derived from basic physical principles can be used for the main other cardiac cell types, a useful property for some model-based signal or image processing applications. The electrical activity of cardiac Purkinje fibres is reconstructed using particular values of the parameters. This model of the membrane excitation mechanism and intracellular calcium dynamics describes the principal ionic current underlying autorhythmicity; calcium uptake and release from the sarcoplasmic reticulum; effects of the binding of calcium on myoplasmic proteins which affect the Nernst potential of calcium, and then the membrane potential. The model allows realistic modelling of cardiac Purkinje fibres action potential, total ionic current, CICR dependence on intracellular calcium concentrations. Simulations illustrate the role of the inward sodium current as the dominant mechanism underlying pacemaker depolarization during spontaneous activity.

Multi-scale modeling of the follicle selection process in the ovary.

The biological meaning of follicular development is to free fertilizable oocytes at the time of ovulation. The ovulation rate results from an FSH-dependent follicle selection process. In this paper, we designed a multi-scale model of follicular development, where selection arises from the endocrine feedback between the ovaries and pituitary gland and appeals to control theory concepts. Each ovarian follicle is described through a 2D density function giving an age and maturity-structured description of its cell population. The control intervenes in the velocity, gain and loss terms of the conservation law ruling the changes in the density. The model accounts for the changes in the total cell number, growth fraction and global maturity of both ovulatory and degenerating follicles for various intensities of the selection rate. The different selection process outputs (mono- or poly-ovulation, anovulation) predicted by the model are consistent with physiological knowledge regarding vascularization, pituitary sensitivity to ovarian feedback and treatment with exogenous FSH.

A multiscale model for the selection process of ovulatory follicles.

The biological meaning of follicular development is to free fertilizable oocytes at the time of ovulation. The selection of ovulatory follicles in mammal ovaries is an FSH-dependent selection process. In this paper, we design a multi-scale model of follicular development, where selection arises from the feedback between the ovaries and the pituitary gland and appeals to control theory concepts. Each ovarian follicle is characterized by a 2D density function giving an age and maturity-structured description of its cell population. The control intervenes in the velocity and loss terms of the conservation law ruling the changes in the density. The numerical outputs of the model, integrated with the finite volume method, are consistent with physiological knowledge.