Regional differences in diabetic patients' pharmacotherapy in Bulgaria.

BACKGROUND: The regional analyses play an important role in understanding a state of diabetes mellitus management and to support informed policy options. They need to be explored in more details in order to ensure an equal patients' access to health care services of the same value and quality. AIM: The aim of this study is to analyze regional differences in a cost of diabetes therapy for insulin users in Bulgaria. MATERIALS AND METHODS: It is a combined prospective and retrospective observational study with duration of 6 months. Diabetic patients on insulin therapy were recruited by 35 endocrinologists. Information about the health care resources used was collected within 3-prospective and 3 retrospective months in 2010 and 2011. The regional cost of illness analysis was performed by calculating the average cost attributable to each individual patient despite the fact that some might not use a particular health care resource. Subgroup analysis was performed for hospitalized patients. RESULTS: A detailed analysis revealed cost differences in the regions, especially with more vulnerable population like Burgas and Pleven regions. Another reason for the cost differences is the type of insulin or type of therapy. Our study confirms the fact that the hospitalizations are the major cost driver. Rising diabetes prevalence and associated costs, including hospitalizations and management of diabetes complications, are a growing concern. The last possible reason for regional differences is the patients' characteristics and therapy differences. We add evidence demonstrating that the patients on insulin and OAD consume more resources including hospitalizations and suffer from more complications of diabetes. CONCLUSIONS: Reasons for regional differences might have different origin as there are various population characteristics, type of therapy, socio economic status and others.

Screening of thermotolerant yeasts as producers of superoxide dismutase.

A screening procedure for highly thermostable yeast superoxide dismutase was developed. Growth yields at various temperatures were estimated for ten mesophilic and thermotolerant strains, belonging to the genera Saccharomyces, Kluyveromyces and Pichia. Higher yields at 45 degrees C were obtained for K. lactis 90-3 and 90-4. A correlation between the ability to grow at higher temperature and the thermostability of the superoxide dismutase enzyme synthesized was observed. A comparison of the operational stability of the superoxide dismutase of all tested strains suggests that the enzyme of K. lactis strains was more thermostable than that of the other tested microorganisms.

Role of superoxide dismutase in the oxidation of N-alkanes by yeasts.

Yeast microorganisms from Candida genus are investigated for their superoxide dismutase (SOD) and catalase activity during cultivation on N-alkanes. The later caused a considerable increase of Cu/Zn SOD activity of yeast cells in comparison with glucose. A correlation between SOD and catalase activity existed. It is further observed that cells of Candida lipolytica 68-72 which contain a high level of Cu/Zn SOD were more resistant to lethality of exogenous O2-. An over-production of Cu/Zn SOD during the assimilation of N-alkanes by yeasts is also connected to their considerable resistance to increased concentrations of Cu2+ and Zn2+ ions in the nutrient medium. The results are consistent with the assumption that the enhanced resistance of yeast cells to O2- and high concentrations of Cu2+ and Zn(2+)-ions are due to the increased activity of Cu/Zn SOD and that SOD is involved in the protection of some cellular components. Polyacrylamide gel electrophoresis of Candida lipolytica cell-free extracts revealed the same chromatic bands of SOD activity under growth on glucose and N-alkanes. The type of the carbon source used from yeast cells as a single source of carbon and energy had no influence on the SOD profile of the cell.

[The effect of an aortocoronary bypass on the physical capacity of drug-stabilized patients with unstable angina pectoris]. / Efekt na aorto-koronarniia bai-pas vurkhu fizicheskiia kapatsitet pri medikamentozno stabilizirani bolni ot nestabilna angina pectoris.

To 51 patients with unstable angina pectoris a submaximum symptom-limited bicycle ergometry [correction of veloergometric] test was performed 3 to 6 days after stabilization by medicamentous treatment was achieved and 2 to 6 months after an aortocoronary bypass had been accomplished. During the first veloergometric test myocardial ischemia was induced in all patients--9 patients were in the IV, 18--in the III and 24--in the II functional class according to NYHA. During the second veloergometric test myocardial ischemia was induced only in 5 patients. At the end of the first year after the aortocoronary bypass had been performed 45 (88.2%) of the patients were without complaints. The predictive value of the positive veloergometric test after an aortocoronary bypass for a poor prognosis is 80% and that of the veloergometric test without induced myocardial ischemia for a favorable prognosis is 95.6%. Aortocoronary bypass in combination with medicamentous treatment improves the symptomatic state, physical capacity and the prognosis of patients with unstable angina pectoris up to the end of the first year to a considerably greater degree than the medicamentous treatment alone.

[The early bicycle ergometry test in drug-stabilized patients with unstable angina pectoris--the correlation with coronary angiography]. / Ranen veloergometrichen test pri medikamentozno stabilizirani bolni ot nestabilna angina pectoris--korelatsiia s koronarnata angiografiia.

The relation between the results of the early submaximal symptom-limited bicycle ergometry [correction of veloergometric] test and coronary angiography were examined in 127 patients with unstable angina pectoris stabilized by medicaments. In 19 (15.0%) patients the test was negative and in 108 (85%) patients the test was positive (angina pectoris and/or ST depression greater than or equal to 0.1 mV at 80 ms after the point J of the ECG). Between the results of the early bicycle ergometry [correction of veloergometric] test and the coronary angiography, performed soon after the test, there was a close correlation. By using strict criteria or a combination of criteria for assessment of residual ischemia the test can with great accuracy differentiate the patients with multivascular from those with monovascular disease or with healthy coronary vessels.

[Determination of the transaortic valve gradient in aortic stenosis by continuous Doppler echocardiography]. / Opredeliane na transaortniia klapen gradient pri aortna stenoza s neprekusnata doplerova ekhokardiografiia.

A correlative study was carried out between the transvalvular aortic gradient determined by continuous wave Doppler echocardiography and by cardiac catheterization (retrograde or transseptal) in 41 patients with proved by invasive methods aortic valvular stenosis of different degree with or without accompanying aortic incompetence (light, moderate or severe). A considerable correlation was found between the transvalvular aortic gradient determined by the two methods (r = 0.75). In spite of that in considerable number of cases there is overestimation or underestimation of the transvalvular aortic gradient determined by Doppler echocardiography compared with the one determined by cardiac catheterization. The overestimation of the transvalvular aortic gradient determined by Doppler echocardiography is due to the accompanying aortic incompetence of greater degree and to the condition that the gradient determined by Doppler echocardiography is maximum instantaneous while the one determined by cardiac catheterization is peak to peak and is principally of lower values. The underestimation of the transvalvular aortic gradient is due to the presence of considerable left ventricular dysfunction and technical faults in the Doppler echocardiographic examination.

[Indications for and the postoperative results of mitral valve prosthesis]. / Pokazaniia i sledoperativni rezultati pri protezirane na mitralnata klapa.

The influence of 20 hemodynamic and clinical indices on the postoperative results was studied in 528 patients with mitral valve prosthetics. One year after the operation 78.7% of the patients are with improved functional capacity, 18.8% are without change and 2.5% are in worse condition. The lack of improvement correlates moderately with the postoperative complications (r = 0.4701) and to a larger degree with the number of patients in the II functional class before the operations (r = 0.7342). The deterioration of the functional capacity is in relation to the complications by operations on the tricuspid valve (r = 0.8773), but there is also considerable correlation with the low ejection fraction (r = 0.6425), previous commisurotomy (r = 0.5871) and uncorrected tricuspid valvular disease (r = 0.6314). The operative lethality rate is 6.25%.

[Left atrial myxoma descending deeply into the cavity of the left ventricle]. / Miksom na liavoto predsurdie, spuskasht se dulboko v kukhinata na liavata kamera.

A female patient, aged 59 is reported with a myxoma of the left auricle, pedunculated deep in left cardiac ventricle. Myxoma was echocardiographically diagnosed and confirmed by left atriography. On the fourth day after the diagnosis of myxoma, with a high efficiency of all examinations and organizational measures the patients was successfully operated.

Determinants of the left ventricular function in patients with coronary heart disease: a multivariate approach.

251 patients with coronary heart disease (CHD) and a control group of 32 normal persons were examined with the purpose of establishing the determinants of the left ventricular function and comparing these determinants with the functional significance of coronary stenosis. The subjects were divided into four groups: I--controls; II--patients with normal left ventricular function (EF more than 60%); III--patients with impaired LV function (EF less than 60%) and Group IV--patients with left ventricular aneurysm. Nine parameters were obtained by multivariate discriminant analysis, which characterize and classify the left ventricular function: the ejection fraction (EF), angina pectoris, exercise ECG, left ventricular end-diastolic pressure, mean velocity of circumferential fibre shortening, left ventricular functional index, longitudinal shortening, LV systolic pressure/systolic volume ratio, and coronary index. On the basis of these parameters, all the normal persons, 88% of Group II, 92% of Group III and 72% of Group IV were classified correctly. The study proves that there is a good correlation between the EF and the haemodynamic and angiocardiographic parameters. The complex left ventricular function index facilitates the prognosis of surgical results. Abnormalities in left ventricular function cannot be reliably assessed by the coronary index values alone.

[Comparison between the loading test and selective coronary angiography in stenocardia]. / Supostavka mezhdu testa s natovarvane i selektivnata koronarografiia pri bolni sus stenokardiia.

The results from the step-wise loading test to 75 per cent of the age maximum pulse rate, performed by veloergemeter or thread-mill in 52 patients (9 females and 43 males, II of them with atypical chest pain and II with stenocardia) were juxtaposed to the data from the selective coronarography. It was established that the a reduction of ST segment greater than I mm and the appearance of precordial pain, degree III by the five-grade scale, have almost identical specificity (70% and 64% resp) and a predicting value of the positive result (68% and 70% resp) and a slightly higher sensitivity to pain (68% and 84% resp) in the detection of coronary stenosis greater than 50 per cent of the diameter of a main coronary vessel. The combination of the signs precordial pain degree III and/or ST reduction greater than I mm and/or elevation of ST greater than 2 mm, with same predicting value (67%) maintained, but with a considerably enhanced sensitivity (96%) proved to be most adequate as a criterion of the positive test. A reduction of ST segment greater than 22 mm is characterized by decrease of sensitivity (40%) but with a considerable increase of specificity (96%). The positivation of that sign suggests the presence mainly of a multibranch disease. The patients with coronary stenosis greater than 50%, rarely reach a physical capacity over 100 wt (7 x oxygen consumption) and a product of the maximum reached pulse rate and systolic blood pressure over 20 000 as compared with those without stenosis, but no difference among the patients with one-branch and multi-branch disease was established. The electrocardiographic changes in the patients with a true positive test with loading is more often retained after 4th minute of the rehabilitation phase as compared with those of the patients with false-positive test. Evidence exists to admit that the predicting value of the positive test is poorer in the patients with atypical pains and females.

[Echocardiographic diagnosis of congestive cardiomyopathy associated with mitral regurgitation]. / Ekhokardiografska diagnostika na kongestivna kardiomiopatiia, suchetana s mitralna regurgitatsiia.

Echocardiographic findings are comparatively analyzed in 25 patients with congestive cardiopathy, combined with mitral regurgitation, a control group of healthy and 10 patients with volume loaded left ventricle with rheumatic "pure" mitral insufficiency. Some discrepancies were established in the usual echocardiographic characteristics of congestive cardiomyopathy in the patients with CCMP, combined with significant mitral insufficiency: normal, even increased amplitude of movement of the interventricular septum in the absence of systolic increase of the septal thickness. The differentiation between the rheumatic mitral insufficiency and mitral insufficiency in case of congestive myocardiopathy is difficult, due to the considerable differences in the functional Echo-C characteristics of left ventricle and morphological characteristic features in mitral echogram.

[Hemodynamic study of postinfarct left ventricular aneurysm]. / Khemodinamichon izsledvane na sledinfarktnata liavokamerna anevrizma.

With a view to the determination of the effect of the size and localization of cardiac aneurysm upon left-ventricular function and the indications for surgical treatment--35 patients with aneurysms of anterior and posterior walls were complexly examined--hemodynamically, angiocardiographically and coronarographically. A method was applied for the determination of the area of anterior aneurysms. The hemodynamics and cardiac functions were established to be pathologically changed in cardiac aneurysm with an area over 25% of the ventricular surface, with a quickly growing risk for surgical treatment with a surface over 60%. The gravest changes were established in case of anterior aneurysms. The possibilities of faults are discussed as well as of the limited significance of the generally accepted parameters of left ventricular function--end diastolic pressure, end diastolic volume, expulsion fraction and the mean velocity of circumferential contraction along the equatorial plane--in the patients with cardiac aneurysm. The high significance of the changes in the local kinetics is confirmed (percentage contraction of the three main axes and their six semi-axes), both for the residual myocardium and aneurysm. Critical values for the parameters applied are proposed, when the surgical treatment is contraindicated or is with a high risk.

[Possibility of studying the specific stimulation-conduction system of the heart]. / Vuzmozhnost za izsledvane spetsifichnata vuzbudno-provodna sistema na surtseto.

The author carried out a survey on a new method for functional diagnostics--recording of the Hiss bundle potentials. The investigation method is described as well as the normal values of electrogram of the Hiss bundle. The clinical significance of the most important indications for the investigation are discussed, namely: 1. Various forms of atrio-ventricular and ventricular disorders of the stimulation-conductivity process. 2. Indistinct rhythm disorders. 3. Diagnostics of the paranodal stimulation conductivity. 4. Pharmacological studies.