"Zeus" a new oral anticoagulant therapy dosing algorithm: a cohort study.

The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.

Fast-electron transport and heating of solid targets in high-intensity laser interactions measured by K alpha fluorescence.

We present experimental results on fast-electron energy deposition into solid targets in ultrahigh intensity laser-matter interaction. X-ray K alpha emission spectroscopy with absolute photon counting served to diagnose fast-electron propagation in multilayered targets. Target heating was measured from ionization-shifted K alpha emission. Data show a 200 microm fast-electron range in solid Al. The relative intensities of spectrally shifted Al K alpha lines imply a mean temperature of a few tens of eV up to a 100 microm depth. Experimental results suggest refluxing of the electron beam at target rear side. They were compared with the predictions of both a collisional Monte Carlo and a collisional-electromagnetic, particle-fluid transport code. The validity of the code modeling of heating in such highly transient conditions is discussed.

Prothrombin evaluation as obtained by kinetics studies of antigen-antibody reaction in a laser nephelometer.

Laser nephelometry is a technique which allows the evaluation of the concentration of several serum proteins and clotting factors. By means of this technique it is also possible to study the kinetics of the reaction between antigen and antibody. We studied the kinetics of the reaction between prothrombin and an antiprothrombin antiserum using several prothrombins namely: Prothrombin Padua, prothrombin Molise, which are two congenital dysprothrombinemias, cirrhotic, coumarin or normal prothrombins. Different behaviors in the kinetics of the reactions were shown even when the concentration of prothrombins was about the same in all plasma tested. These differences were analyzed by means of a computer (Apple II 48 RAM) programmed to solve four unknown equations (Rodbard's equation). From the data so obtained one can see that when voltages at the beginning and at the end of the reaction are in all cases about the same, a clear difference in the time required to reach half the maximum value of the voltage can still be demonstrated. This parameter, which is expressed in minutes, is longer in coumarin and prothrombin Molise than in controls. On the contrary it is shorter in prothrombin Padua and has about the same value of controls in the cirrhotic patient. Moreover the time at which the maximum rate is obtained is longer in coumarin and prothrombin Molise than in controls and shorter in liver cirrhosis and prothrombin Padua. In conclusion data obtained show that coumarin prothrombin behaves in a different way from cirrhotic prothrombin and also that there is a different behaviour between the two congenital dysprothrombinemias.

The role of laser nephelometer in the study of abnormal clotting factors: characterization of two abnormal antithrombins (AT III Padua and AT III Padua2).

The immunologic concentration of two abnormal antithrombins III (AT III), namely antithrombin III Padua (AT III Padua) and antithrombin III Padua2 (AT III Padua2) and the kinetics of the reaction of these two ATs III with an anti AT III antiserum was investigated by means of a laser nephelometer. The immunologic concentration of these two AT III both in presence (0.2 IU/mL) or absence of heparin was normal. On the contrary, the analysis of kinetics behavior demonstrated that AT III Padua is radically different from pooled normal plasma both in presence or in absence of heparin. This was not the case for AT III Padua2, which showed no difference from pooled normal plasma regardless of the presence or absence of heparin. Both abnormal antithrombins III reached the plateau of the reaction at about the corresponding value of pooled normal plasma, indicating a normal antigen level. These experimental data were analyzed by means of a computer (Apple II 48 RAM) programmed to solve a four unknowns equation (Rodbard's equation). This analysis showed that the time needed to reach half of the maximum voltage, i.e., the parameter C, which is expressed in minutes, is clearly longer in the case of AT III Padua samples (heparinized or not) as compared with pooled normal plasma. Moreover, the time at which the maximum rate was reached was also longer. On the contrary, in the case of AT III Padua2 there is no difference from pooled normal plasma. These data confirm the view that a different kind of defect is present in these two AT III abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian temporal structure evaluated by automatic monitoring.

A few aspects of the circadian time structure were evaluated in a young healthy woman, with a special reference to arterial pressure and body temperature. Both parameters were estimated by the use of automatic equipments. The present study evidences the importance and the advantages of autorhythmometry (which should be applied in every instance, but can not be omitted when measuring arterial pressure) and automatic monitoring (which warrants an excellent reproducibility of measurements).

Circadian temperature rhythm in intact, sham operated, gonadectomized rats.

Thirty-six CS rats (18 females and 18 males) have been studied: 22 gonadectomized (11 males and 11 females), 6 sham operated (3 males and 3 females) and 8 intact rats (4 males and 4 females). Three series of rectal temperature measurements have been performed: in the first one the animals were housed under strictly usual environment conditions (as far as the housing and lighting regimen was concerned); in the second one the animals were housed in metabolic cages in LD 12:12; in the third one the animals were housed in metabolic cages in DD. The mesor of temperature rhythm was always lower in ovariectomized than in intact rats, and always higher in castrated than in intact rats.

Circadian rhythm of rectal temperature in young and adult rats under different conditions of food access.

The circadian rhythm of rectal temperature has been evaluated in young (1-month old) and adult (9 month old) female Wistar rats. The animals were housed in metabolic cages in LD 12:12 having food in powder and tap water ad libitum. The single cosinor analysis showed high statistical significance (at least p less than 0.01) in order to circadian rhythm of rectal temperature. The comparisons of the mean cosinor evaluations of circadian rhythm in the 2 differently aged groups do not show significantly different parameters for a 95% of confidence. Two more groups of animals, of the same age, strain, sex and environmental conditions, have been studied. These rats had food admittance in the first 4 h of the dark span (1200.1600) only. In this case too, no significant difference has been evidenced between young and adult rats in any parameters of circadian rhythm for a 95% of confidence. Therefore the 2 pools of animals (young and adult one together because of the already demonstrated lack of difference between the 2 groups) in ad libitum and restricted feeding regimen have been compared. No significant difference has been shown between the 2 groups regarding mesor, while Hotelling's test showed significant differences for amplitude and acrophase.