[ECONOMIC BURDEN AND CURRENT STATUS OF THE DRUG SUPPLY MANAGEMENT FOR IMMUNE INFLAMMATORY DISEASES (BY EXAMPLE OF ULCERATIVE COLITIS AND CROHN'S DISEASE)].

AIM: to estimate the quality and availability of medical care for patients with ulcerative colitis (UC) and Crohn's disease (CD), to assess the impact of the economic burden of these diseases on the healthcare budget of Russia and to systematize the main problems in the organization of medical care and drug supply for patients with inflammatory bowel diseases (IBD). Regional IBD databases (2016-2018), official statistical databases, costs of treatment and results of expert interviews with specialists in IBD were used in the study. The analyzed databases showed 104,668 patients with UC in Russia in 2018 (prevalence rate 71 per 100,000 people) and 66,647 patients with CD (prevalence rate of 45 per 100,000 people). The economic burden including agents for biologic therapy (ABT) for the UC was 39.54 billion rubles a year (495 rubles per capita), and CD - 32.98 billion rubles a year (378 rubles per capita). It requires an additional 9.87 billion rubles annually for UC and 9.20 billion rubles annually for CD patients to provide the complete supply with ABT. The annual burden of IBD is 72.52 billion rubles, which is comparable to the costs of other socially significant diseases, including malignant tumors. It shows the high social and economic value of IBD for the country. The main problems of medical care and drug supply for IBD patients are the mismatch of official statistical data and real IBD prevalence in Russia due to absence of comprehensive register and the insufficient supply with ABT due to limited funding. A federal center for IBD should be founded for better quality of registration, for the precise monitoring and for the active management of personal drug supply.

[Rehabilitation program for patients with low anterior resection syndrome]. / Reabilitatsionnaya programma dlya bol'nykh rakom pryamoi kishki s sindromom nizkoi perednei rezektsii.

Surgical treatment of rectal cancer and sphincter-preserving low anterior resection results to evacuation disorders («low anterior resection syndrome¼ - LARS). There are no clinical recommendations for the treatment of patients with LARS as well as a rehabilitation program for them. OBJECTIVE: To develop a rehabilitation program for patients with low anterior resection syndrome. MATERIAL AND METHODS: The investigation was performed at 2 stages. During the first stage, 29 patients with LARS (17 (58.6%) men, mean age of the participants' 61.5±9.5 years), 12 (41.4%) women (mean age 61.2±7.8 years) were examined and received the course of conservative treatment with the use of biofeedback-therapy performed by the standard protocol. On the second stage, 17 patients (mean age 61.4±12.7 years) - 9 (52.9%) men, 8 (47.1%) women received biofeedback therapy in combination with tibial neuromodulation (TNM). Functional state of the rectum and the locking apparatus in all patients were evaluated by anorectal manometry: sphincterometry and studies of the reservoir function of the rectum before and after treatment. RESULTS: The developed complex of rehabilitation measures led to improved treatment results for patients with rectal cancer by improving the quality of life after low anterior resection, reducing the manifestations of LARS (by 47.8%). Stable positive results of treatment were maintained in 36.4% of patients, positive dynamics from the treatment according to the LARS scale decreased slightly in 54.5%, deterioration of indicators in 3-6 months after conservative rehabilitation was registered in 9.1% of cases. At the first stage maximal squeeze pressure improvement was reached in the whole cohort (p=0.047), at the second stage these trend was seen only for women for the pressure values at rest (p=0.01) and during squeeze (p=0.025). The data obtained allowed us to recommend a repeat course of treatment to 63.6% of patients. The authors modified and optimized a special complex of physical therapy for the rehabilitation of patients both in a medical institution and at home. These exercises are aimed at improving the functional state of the pelvic floor muscles and sphincter apparatus. CONCLUSION: Rehabilitation program for patients with low anterior resection syndrome should include: 1) biofeedback therapy to improve the holding function; 2) biofeedback therapy aimed at improving the reservoir function and sensitivity of the rectum to filling; 3) tibial neuromodulation. This program may help improving the contractility of the anal sphincter and reservoir function of the rectum, as well as the appearance of the urge to defecate.

Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results for 140,767 yeasts were collected from 127 participating investigators in 39 countries from June 1997 through December 2003. Data were collected on 79,343 yeast isolates tested with voriconazole from 2001 through 2003. All investigators tested clinical yeast isolates by the CLSI (formerly NCCLS) M44-A disk diffusion method. Test plates were automatically read and results were recorded with the BIOMIC Vision Image Analysis System. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly via e-mail for analysis. Duplicate (the same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. The 10 most common species of yeasts all showed less resistance to voriconazole than to fluconazole. Candida krusei showed the largest difference, with over 70% resistance to fluconazole and less than 8% to voriconazole. All species of yeasts tested were more susceptible to voriconazole than to fluconazole, assuming proposed interpretive breakpoints of > or =17 mm (susceptible) and < or =13 mm (resistant) for voriconazole. MICs reported in this study were determined from the zone diameter in millimeters from the continuous agar gradient around each disk, which was calibrated with MICs determined from the standard CLSI M27-A2 broth dilution method by balanced-weight regression analysis. The results from this investigation demonstrate the broad spectrum of the azoles for most of the opportunistic yeast pathogens but also highlight several areas where resistance may be progressing and/or where previously rare species may be "emerging."

Variable velocity liquid flow EPR applied to submillisecond protein folding.

We have developed a variable velocity, rapid-mix, continuous-flow method for observing and delineating kinetics by dielectric resonator-based electron paramagnetic resonance (EPR). The technology opens a new facet for kinetic study of radicals in liquid at submillisecond time resolution. The EPR system (after Sienkiewicz, A., K. Qu, and C. P. Scholes. 1994. Rev. Sci. Instrum. 65:68-74) accommodated a miniature quartz capillary mixer with an approximately 0.5 microliter delivery volume to the midpoint of the EPR-active zone. The flow velocity was varied in a preprogrammed manner, giving a minimum delivery time of approximately 150 microseconds. The mixing was efficient, and we constructed kinetics in the 0.15-2. 1-ms time range by plotting the continuous wave EPR signal taken during flow versus the reciprocal of flow velocity. We followed the refolding kinetics of iso-1-cytochrome c spin-labeled at Cysteine 102. At 20 degrees C, upon dilution of guanidinium hydrochloride denaturant, a fast phase of refolding was resolved with an exponential time constant of 0.12 ms, which was consistent with the "burst" phase observed by optically detected flow techniques. At 7 degrees C the kinetic refolding time of this phase increased to 0.5 ms.

Q-band ENDOR (electron nuclear double resonance) of the high-affinity ubisemiquinone center in cytochrome bo3 from Escherichia coli.

Electron nuclear double resonance (ENDOR) was performed on the protein-bound, stabilized, high-affinity ubisemiquinone radical, QH*-, of bo3 quinol oxidase to determine its electronic spin distribution and to probe its interaction with its surroundings. Until this present work, such ENDOR studies of protein-stabilized ubisemiquinone centers have only been done on photosynthetic reaction centers whose function is to reduce a ubiquinol pool. In contrast, QH*- serves to oxidize a ubiquinol pool in the course of electron transfer from the ubiquinol pool to the oxygen-consuming center of terminal bo3 oxidase. As documented by large hyperfine couplings (>10 MHz) to nonexchangeable protons on the QH*- ubisemiquinone ring, we provide evidence for an electronic distribution on QH*- that is different from that of the semiquinones of reaction centers. Since the ubisemiquinone itself is physically nearly identical in both QH*- and the bacterial photosynthetic reaction centers, this electronic difference is evidently a function of the local protein environment. Interaction of QH*- with this local protein environment was explicitly shown by exchangeable deuteron ENDOR that implied hydrogen bonding to the quinone and by weak proton hyperfine couplings to the local protein matrix.