Harukazu Tsuruta

Mathematical model of cardiovascular mechanics for diagnostic analysis and treatment of heart failure: Part 1. Model description and theoretical analysis.

The planning of drug therapy for heart failure should involve both the diagnostic analysis of the patient’s defective state and a prediction of the drug effects on the identified state. We have devised a mathematical model of cardiovascular system mechanics, on which both quantitative diagnosis and evaluation of drug effects can be made. The model was composed of systemic and pulmonary circulatory networks including the dynamics of the left and right ventricles. The model of the ventricles can represent both systolic and diastolic problems in heart failure through the parameters of ventricular contractility and diastolic stiffness. Each vascular network was composed of arterial and venous resistances and total vascular capacitance. Patient’s ventricular and vascular parameters were estimated simultaneously from the clinically measurable haemodynamic variables based on the model. Despite the simplicity of the model, the results showed good agreement with clinical and experimental data. The clinically significant haemodynamic classification of heart failure by Forrester et al. (Forrester et al., 1977) was simulated well by the model. This model provides a useful basis for analysing pathophysiological states in heart failure and evaluating drug effects on the disease.

Difference equation model of the entrainment of myocardial pacemaker cells based on the phase response curve

As a method for investigating entrainment phenomena found in biological oscillations, a model is presented which is formulated as a set of difference equations on the basis of “phase response curves” of biological oscillators. Properties of the model are discussed and synchronization of cardiac pacemaker cells to the external periodic stimuli is analyzed by use of the model. It is shown that the model is reducible to an equivalent system to the mathematical neuron model of Nagumo et al. under a specific parametric condition of the phase response curve. As an application to the cardiac arrhythmias, the model of ventricular parasystoles studied by Moe et al. is described mathematically in terms of a system of difference equations. In addition, a more comprehensive model of ventricular parasystoles is proposed.

Polychotomization of continuous variables in regression models based on the overall C index

BackgroundWhen developing multivariable regression models for diagnosis or prognosis, continuous independent variables can be categorized to make a prediction table instead of a prediction formula. Although many methods have been proposed to dichotomize prognostic variables, to date there has been no integrated method for polychotomization. The latter is necessary when dichotomization results in too much loss of information or when central values refer to normal states and more dispersed values refer to less preferable states, a situation that is not unusual in medical settings (e.g. body temperature, blood pressure). The goal of our study was to develop a theoretical and practical method for polychotomization.MethodsWe used the overall discrimination index C, introduced by Harrel, as a measure of the predictive ability of an independent regressor variable and derived a method for polychotomization mathematically. Since the naïve application of our method, like some existing methods, gives rise to positive bias, we developed a parametric method that minimizes this bias and assessed its performance by the use of Monte Carlo simulation.ResultsThe overall C is closely related to the area under the ROC curve and the produced di(poly)chotomized variables predictive performance is comparable to the original continuous variable. The simulation shows that the parametric method is essentially unbiased for both the estimates of performance and the cutoff points. Application of our method to the predictor variables of a previous study on rhabdomyolysis shows that it can be used to make probability profile tables that are applicable to the diagnosis or prognosis of individual patient status.ConclusionWe propose a polychotomization (including dichotomization) method for independent continuous variables in regression models based on the overall discrimination index C and clarified its meaning mathematically. To avoid positive bias in application, we have proposed and evaluated a parametric method. The proposed method for polychotomizing continuous regressor variables performed well and can be used to create probability profile tables.

Mathematical model of cardiovascular mechanics for diagnostic analysis and treatment of heart failure: Part 2 analysis of vasodilator therapy and planning of optimal drug therapy

Using a mathematical model of cardiovascular mechanics, various complicated responses to vasodilator therapy for heart failure have been well accounted for through common logic: (i) the differential effects of various vasodilators on cardiac output; (ii) the opposite response of cardiac output to sodium nitroprusside in a normal state and heart failure state; (iii) the different responses of cardiac index, arterial pressure and left ventricular end-diastolic pressure to hydralazine in different types of heart failure. The response to combined vasodilator-inotropic agent therapy was simulated well by the model. The optimal therapeutic regimen was then formulated to simultaneously control the cardiac output, systemic and pulmonary arterial and venous pressures, and the degree of coronary ischaemia by multiple drug delivery, and the problem was solved using the model. We conclude that the model provides a useful basis for obtaining a guidance for more appropriate therapeutic regimen in heart failure.

Analysis of Medical Equipment Management in Relation to the Mandatory Medical Equipment Safety Manager (MESM) in Japan

Half a decade has passed since the fifth revision of the medical law and mandatory appointment of a medical equipment safety manager (MESM) in hospitals in Japan. During this period, circumstances have changed regarding maintenance of medical equipment (ME). We conducted a survey to examine these changes and the current situation in ME management. Maintenance of ME and related work were found to have increased in many hospitals, but the number of clinical engineering technologists (CETs) has only slightly increased. The appointed MESM was a CET or physician in most hospitals. In hospitals where physicians were appointed as the MESM, 81% had operation managers. Many respondents commented that it was difficult for one person to cover all the tasks required by the MESM, due to a lack of knowledge, too much work, or other reasons. This suggests the importance of an operation manager for ME to work under the MESM.

Computer assisted instruction for therapy of heart failure based on simulation of cardiovascular system

Adequate treatment of cardiac failure should reflect both clinical rules and quantitative evaluation of hemodynamics. For the latter we assumed an extensive model of heart and vessels: For the left and right ventricles the EMAX models were assumed with the parameters of contractilities and diastolic compliances. The model of the vessels was composed of systemic and pulmonary vascular networks with arterial, capillary and venous segments. Heart failure of various types was simulated by the model and the optimal therapeutic regimen was formulated. The cardiovasular parameters of patients with heart failure could be esimated from the hemodynamic measurements through the model and the optimal therapy was computed with the technique of nonlinear programming.The simulation thechnique was incorporated in the computer assisted instruction system based on the clinical emirical rules. The program was written with TURBO PASCAL for a microcomputer with CPU 80286. The response time was within a tolerable range for use in the clinical practice.

A unifying approach to the shape and change-point hypotheses in the discrete univariate exponential family

A unifying approach to the shape and change-point hypotheses is extended generally to a discrete univariate exponential family. The maximal contrast type tests are newly proposed for the convexity and sigmoidicity hypotheses based on the complete class lemma of tests for the restricted alternatives. Those tests are also efficient score tests for the slope change-point and inflection point models, respectively. For each of those tests the successive component statistics are the doubly- and triply-accumulated statistics. They have nice Markov properties for the exact and efficient recursion formulae for calculating the p -value. Further the sum of squares of the component statistics are developed as the cumulative chi-squared statistics for the directional goodness-of-fit tests of the dose-response model. Therefore the interesting applications will be in monitoring of spontaneous reporting of the adverse drug events and the directional goodness-of-fit tests.

Study of electrical power facilities and measures for planned outages in Japanese hemodialysis clinics after the Great East Japan Earthquake.

The Great East Japan Earthquake on 11 March 2011 caused major damage in northeastern Japan. The Kanto region experienced a massive electrical power shortage in the summer of 2011. A questionnaire was submitted to 354 hemodialysis clinics in Kanagawa prefecture and the Tokyo metropolitan area, excluding isolated islands, and 176 responses were analyzed (49.7%). The questions included evaluation of the availability of a private electricity generator, countermeasures in case of a planned outage, awareness of saving electricity, and improvement of safety of medical devices or electrical facilities after the earthquake. Only 12% of the clinics had private electricity generators and many clinics had no plans to introduce this facility. However, 96% of the clinics had established countermeasures to deal with a planned outage. Many clinics planned to provide dialysis on a different day or at a different time. All clinics had tried hard to establish procedures to save electricity in the summer of 2011, and 84% of the clinics had reconsidered and improved the safety of medical devices or electricity facilities after the earthquake. These results show that the awareness of crisis management was greatly improved in the wake of the earthquake.

An algorithm for a new method of change-point analysis in the independent Poisson sequence

Summary Step change-point and slope change-point models in the independent Poisson sequence are developed based on accumulated and doubly-accumulated statistics. The method for the step change-point model developed in Section 2 is an alternative to the likelihood ratio test of Worsley (1986) and the algorithm for p-value calculation based on the first-order Markov property is the same as that given there. Different algorithms for the non-null distribution and inference on the change-point itself are, however, newly developed and a Pascal program is given in the Appendix. These methods are extended to the slope change-point model in Section 3. The approach is essentially the same as that of Section 2 but the algorithm is now based on the second-order Markov property and becomes a little more complicated. The Pascal program related to the slope change-point model is supported on the website, URL: https://corec.meisei-u.ac.jp/labs/hirotsu/.

A Risk Model for Surgical Site Infection in the Gastric Cancer Surgery Using Data of 790 Patients

Background: Understanding risk factors of surgical site infections (SSIs) in gastrectomy is important to provide the best treatment for the patients with gastric cancer. Methods: This is a retrospective observational study using the medical records of 790 patients with gastrectomy from 2005 through 2009. SSIs were classified into incisional SSIs (iSSIs) and organ/space SSIs (o/sSSIs). Results: iSSIs and o/sSSIs were detected in 41 (5.2%) patients and 68 (8.6%) patients, respectively. Open surgery was the only independent risk factor (p = 0.028) for iSSIs, while open surgery (p = 0.004), concurrent splenectomy (p < 0.001), operative time ≥220 min (p = 0.009), preoperative body mass index ≥20.8 kg/m2 (p = 0.004) and male gender (p = 0.028) were the independent risk factors for o/sSSIs. We created a risk model for o/sSSIs using these independent risk factors. The C-index model discrimination was 0.84 (p < 0.001), and the calibration of the models demonstrated a linear correlation between the predicted and observed probability. Conclusion: We reported the risk factors of SSIs for gastrectomy. The risk model developed in this study for o/sSSIs pertaining to gastric cancer surgery would contribute to provide guidance for the development of best practices.