Primary bedaquiline resistance in Karakalpakstan, Uzbekistan.

BACKGROUND: Bedaquiline (BDQ) is widely used in the treatment of rifampicin-resistant TB (RR-TB). However, resistance to BDQ is now emerging. There are no standardised regimens for BDQ-resistant TB. This study aims to share experience in managing primary BDQ-resistant TB.METHODS: We performed a retrospective study of patients treated for RR-TB in Karakalpakstan, Uzbekistan, from January 2017 to March 2022. We identified patients with resistance to BDQ with no history of BDQ exposure. We describe baseline characteristics, treatment and follow-up of these patients.RESULTS: Twelve of the 1,930 patients (0.6%) had baseline samples resistant to BDQ with no history of BDQ exposure, 75% (9/12) of whom had been previously treated for TB. Ten (83.3%) were resistant to fluoroquinolones; respectively 66% and 50% had culture conversion by Month 3 and Month 6. The interim treatment outcomes were as follows: unfavourable treatment outcomes (3/12, 25%), favourable outcomes (2/12, 17%); the remaining seven (58%) were continuing treatment.CONCLUSIONS: A large proportion of the cases had previously been treated for TB and had TB resistant to quinolone. Both patients who had not experienced culture conversion by Month 3 had an unfavourable treatment outcome. Therefore, we recommend monthly monitoring of culture status for patients on treatment regimens for BDQ resistance.

Acquired bedaquiline resistance in Karakalpakstan, Uzbekistan.

BACKGROUND: The WHO recommends the use of bedaquiline (BDQ) in longer, as well as shorter, multidrug-resistant TB (MDR-TB) treatment regimens. However, resistance to this new drug is now emerging. We aimed to describe the characteristics of patients in Karakalpakstan, Uzbekistan, who were treated for MDR-TB and acquired BDQ resistance during treatment.METHODS: We performed a retrospective study of routinely collected data for patients treated for MDR-TB in Karakalpakstan between January 2015 and December 2020. We included patients on BDQ-containing regimens with baseline susceptibility to BDQ who developed BDQ resistance at any point after treatment initiation. Patients resistant to BDQ at baseline or with no confirmed susceptibility to BDQ at baseline were excluded.RESULTS: Of the 523 patients who received BDQ-containing regimens during the study period, BDQ resistance was detected in 31 patients (5.9%); 20 patients were excluded-16 with no prior confirmation of BDQ susceptibility and 4 who were resistant at baseline. Eleven patients with acquired BDQ resistance were identified. We discuss demographic variables, resistance profiles, treatment-related variables and risk factors for unfavourable outcomes for these patients.CONCLUSION: Our programmatic data demonstrated the acquisition of BDQ resistance during or subsequent to receiving a BDQ-containing regimen in a patient cohort from Uzbekistan. We highlight the need for individualised treatment regimens with optimised clinical and laboratory follow up to prevent resistance acquisition.

[The Factor Stabilizing the Bioluminescence of PVA-Immobilized Photobacteria].

Immobilization of photobacteria in the cryogel of polyvinyl alcohol (PVA) was carried out. Immobilization was found to result in increased intensity and stability of bioluminescence. The elements determining the stability of bioluminescence were investigated. Selection of the strain was found to be of the highest importance. Among immobilized cells, Photobacterium phosphoreum exhibited the most intense and prolonged light emission, while Vibrio harveyi showed the least one. The technological procedures for cryogenic immobilization of photobacteria were determined. The role of the environment of gel formation in the preservation of the bioluminescence activity was determined. In the gels formed in rich medium for submerged cultivation of photobacteria, almost 100% luminescence activity was preserved, while light emission was considerably prolonged. Bioluminescence intensity of the preparations was shown to depend significantly on pH of the incubation medium. The pH shift to acidic values during prolonged incubation of immobilized cells was shown to be one of the factors of bioluminescence quenching. The stress effects of cryogenic immobilization were found to have an insignificant effect on the temperature profile of bioluminescence. Decreased reduction rate of the luciferase flavin substrate was shown to be a possible reason for bioluminescence quenching.

[Russian experience of lacosamide (vimpat) usage in treatment of uncontrolled focal epilepsy]. / Rossiiskii opyt primeneniya lakosamida (vimpat) pri lechenii patsientov s nekontroliruemoi fokal'noi epilepsiei.

Many patients with epilepsy receive treatment in polytherapy. Selection of antiepileptic drugs (AEDs) for the combination should be carried out in accordance with the principles of rational polytherapy, taking into account the mechanism of action, pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs. Along with levetiracetam, gabapentin, vigabatrin and pregabalin, lacosamide (LCM) shows superior PK profile in rating of all AED and can be combined with any of them. The goal of this study was to evaluate efficacy and tolerability of LCM in patients with uncontrolled partial onset seizures (POS) in routine clinical practice. METHODS: 181 patient's charts from 14 sites in Russia have been analyzed in retrospective manner. Patients 16 years old and older with POS with or without secondary generalization were included. Documented observation period of up to 12 months after initiation or until discontinuation of LCM therapy. Primary effectiveness variables was retention at Observational Point 3 (approximately 12 months). Other variables were: percentage change from historical baseline in seizure frequency, 50% and 75% treatment response and seizure-free status at the Observational Points 1, 2 and 3 (approximately 3, 6 and 12 months) and incidence and reason of treatment discontinuation. RESULTS: retention rate was high with 89.5% after 12-month observation. The development of seizure frequency showed a continuous decrease in terms of 50%, 75% treatment respond rates and seizure free status. A total of 5 adverse drug reactions leading to discontinuation of LCM therapy were recorded in 5 of 181 patients (2.8%) during the observation period. The high retention rate observed in this retrospective chart review is assumed to indicate a good tolerability and effectiveness of an adjunctive LCM treatment in patients with uncontrolled partial epilepsy in Russia.

Photobiosensors containing luminescent bacteria.

The scientific basis for producing luminescent biosensors containing free and immobilized luminescent bacteria is discussed. Modern technologies for engineering target objects, procedures used to immobilize bacteria in different carriers, as well as procedures for integral and specific biodetection of toxins are presented. Data regarding generation and application of biomonitoring for ecotoxicants derived from natural and genetically engineered photobacterial strains are analyzed. Special attention is given to immobilization of photobacteria in polyvinyl alcohol-containing cryogel. The main physicochemical, biochemical, and technological parameters for stabilizing luminescence in immobilized bacteria are described. Results of the application of immobilized photobacterial preparations both during discrete and continuous biomonitoring for different classes of ecotoxicants are presented.

[Biosensors based on the luminous bacteria Photobaterium phosphoreum immobilized in polyvinyl alcohol cryogel for the monitoring of ecotoxicants].

Immobilization of Photobacterium phosphoreum bacteria in polyvinyl alcohol cryogel was performed in order to develop biosensors used for ecotoxicant biomonitoring. The immobilization procedure, storage, and application of the immobilized cells for biomonitoring were optimized. It was shown that the immobilized cells demonstrate significantly higher stability and a longer duration of light emission than free bacteria. A discrete analysis of heavy metals and chlorophenols was conducted using the obtained biosensor samples.

[Asthenia, emotional disorders and quality of life of patients with multiple sclerosis]. / Asteniia, émotsional'nye rasstroistva i kachestvo zhizni u patsientov s rasseiannym sklerozom.

Objective. The evaluation of the dynamics of asthenia, chronic fatigue syndrome, emotional disorders and quality of life of patients with multiple sclerosis (MS) and to explore the possibility of using idebenon (noben) in treatment of these impairments. Material and methods. We studied 35 patients, 18 men and 17 women, with MS (mean age 36.4±8.86 years, mean disease duration 10.33±6.07 years); 83% of patients had remitting type and others - secondary progressive type. Along with neurological examination, we used the Modified Fatigue Impact Scale (MFIS 21), the Hospital Anxiety and Depression Scale and a quality of life questionnaire (EQ5D). Patients had marked asthenia and chronic fatigue at baseline. The old age of the patients and duration of MS and its severity according to EDSS predicted the higher levels of asthenia, chronic fatigue and anxiety with depression and lower quality of life on EQ5D. All patients received noben in dosage 90 mg daily (30 mg 3 times a day) during 6 months. Results and conclusion. Idebenon (noben) reduced the severity of chronic fatigue syndrome, asthenia and depression in MS patients. The dose used in the study may be regarded as the optimal dose that provides best efficacy with minimal side-effects.

[ATP pool and bioluminescence in psychrophilic bacteria Photobacterium phosphoreum].

Bioluminescence activity and ATP pool were investigated in the culture of psychrophilic bacteria Photobacterium phosphoreum collected-from the exponential and stationary growth phases, as well as immobilized in polyvinyl alcohol (PVA) cryogel. In liquid culture, ATP pool remained at an almost a constant level throughout the luminescence cycle (over 100 h). The ATP pool in the stationary-phase and PVA-immobilizedl cells remained constant throughout their incubation in the medium (over 200 h) and in 3% NaCl solution (over 100 h): Quantitative assessment of integral photon yield and ATP pool indicated that bioluminescence decay in growing or stationary cells was not caused by limitation by the energy substrates of the luciferase reaction. Kinetic and quantitative parameters of emission activity and ATP pool excluded the possibility of formation of the aldehyde substrate for luciferase via reduction of the relevant fatty acids in NADPH and ATP-dependent reductase reaction and its oxidation in the monooxygenase reaction. Our results indicate that the aliphatic aldehyde is not utilized in the process of light emission.

[Possibilities of medical correction of moderate cognitive impairment].

Thirty-four outpatients with moderate cognitive impairment were treated with one of standard extracts of Ginkgo Biloba - EGb761 (memoplant). Memoplant was used in high dosages (240 mg daily) twice a day during three months. Patients were assessed using the Montreal Cognitive Assessment (MoCA), the hospital depression scale and QoL questionnaire EQ5d as well as standard neurological and somatic examination. A statistical analysis of data revealed a significant improvement in most measures, mostly in attention, memory, orientation and visual-spatial/ executive functions as well as in anxiety and depression. The drug is well-tolerated and is recommended for practical use.

[Emotional disorders and quality of life in patients with post stroke asthenia].

An aim of the study was to assess the severity of asthenic syndrome, emotional disorders and quality of life indicators in post stroke patients treated with idebenone (noben). We studied 35 patients aged from 47 to 76 years, mean age 58,85±7,99 years, 21 men and 14 women. The time after stroke was 1-8 years (mean 2,63±1,51 years). The duration of follow-up was 6 months. Patients were examined at baseline and 3 and 6 months after treatment with noben in dose 90 mg daily (30 mg 3 times a day). Patients were examined clinically, the following scales were used as well: the Scandinavian stroke scale, the modified MFIS-21, the hospital anxiety and depression scale (HADS) and EQ5D including VAS. It has been shown that asthenic syndrome negatively influenced quality of life and emotional sphere thus impeding the recovery of daily activities. The follow-up study revealed that the treatment with idebenone in dose 90 mg daily decreased the severity of asthenia and emotional disorders and significantly improved quality of life.

[The use of cerepro (choline alfoscerate) in the treatment of outpatients with chronic progressive cerebrovascular disease].

The main aim of the study was the evaluation of the efficacy and drug safety of cerepro (choline alfoscerate) used for treating outpatients with cerebrovascular disease. Ninety patients with cerebrovascular disease, who had motor, coordination, emotional and cognitive disturbances were enrolled in the study. Sixty patients of the group 1 had stroke, 30 patients (group 2) had chronic ischemic brain disease. All patients received basic therapy (antihypertensive, antiaggregant or anticoagulant, cholesterol-lowering drugs). Cerepro was administrated in combined therapy according to the scheme: 1000 mg cerepro (in 200 ml of the 0.9% NaCl solution) once a day intravenously in drops during 10 days; then 1200 mg daily per os during 6 weeks. We assessed the dynamic of neurological symptoms and restoration of lost functions (MMSE, Feeling-activity-mood test, HDRS, GCI). The results indicate the efficacy of cerepro in outpatients with chronic cerebrovascular disease and stroke. It was demonstrated that cerepro led to improvement of coordination neurological symptoms, cognitive and emotional functions, activity and mood in patients of both groups. Clinical effect was higher in patients after stroke. Cerepro was well tolerated.

[Effect of dopamine agonist pramipexole (mirapex) on tremor, affective disorders and quality of life in patients with Parkinson's disease].

The open 6-month study (the MIRAG study) on the effect of D2/D3 dopamine agonist pramipexole (mirapex) on tremor, affective disorders and quality of life in patients with Parkinson's disease (PD) was carried out. Ninety-eight patients, aged from 42 to 75 years (mean age 63.2+/-10.2 years) were included in the study. Scores on the Hoehn and Yahr scale varied from 1 to 4 (mean 2,5+/-0,8). Seventy percent of patients received levodopa in average dose 351.2+/-279.4 mg; 62% of patients had motor fluctuations and 43% had dyskinesias. Pramipexole was titrated to the effective dose (maximum 3 mg/d, mean 2.1 mg/d). In the end of the study, resting tremor was reduced by 54%, postural and kinetic tremor, as assessed with UPDRS and spirography, by 50% and 15%, respectively. The severity of depressive symptoms measured with the Montgomery-Asberg Scale and a modified version of the Geriatric-Depression Scale (GDS-15) was reduced by 56%. Motor fluctuations and dyskinesias were significantly reduced while cognitive functions were not changed. The clinically significant effect reflected in the reduction of motor and non-motor symptoms was observed in 83% of patients, regardless of disease duration, severity of motor deficit, affective and cognitive disorders,. The drug was well tolerated in all patients, including those older than 70 years. Pramipexole improved quality of life in PD patients due to the attenuation of cardinal motor parkinsonian symptoms as well as symptoms, which were relatively resistant to levadopa, e.g. postural and kinetic tremor, and depression. The therapeutic effect remained for at least 6 months.

[Influence of dopamine agonist pramipexole (mirapex) on tremor, cognitive and affective impairment in patients with Parkinson's disease].

The open 3-month study of influence of D2/D3 dopamine agonist pramipexole on of Parkinson's disease (PD) features, which are relatively resistant to traditional dopaminergic therapy: tremor, affective and cognitive impairment, has been conducted. Ninety-eight patients with PD, aged from 42 to 75 years (mean age 63,2+/-10,2 years), have been included in the study. Twenty percents of patients included were older than 70 years. The Hoehn and Yahr stage varied from 1 to 4 (men stage 2,5+/-0,8). Seventy percents of patients received levodopa (mean dosage 351,2+/-279,4 mg); 62% had motor fluctuations and 43% - dyskinesias. Pramipexole was titrated to effective dose (maximum 3 mg/d, mean 2,1 mg/d). The decrease of resting tremor by 50% and postural and kinetic tremor (assessed with the UPDRS and spiralography) by 37% was noticed to the end of 3 month. The severity of depressive symptoms measured with the Montgomery-Asberg scale and a modified version of the Geriatric Depression scale was reduced by one third. The statistically significant decrease of motor fluctuations and dyskinesias, increase of verbal fluency (but not other cognitive functions) were also found. The clinically significant effect of reducing of motor and non-motor symptoms was seen in 86% patients regardless of their age, illness duration, severity of motor deficit and affective and cognitive disturbances. The fair tolerability of the drug was shown including patients older than 70 years.

[The use of the drug ginos in the treatment of out-patients with chronic progressive brain disorders].

Ginos, a derivative of extract Ginkgo Biloba, was administered to 100 patients, aged from 45 to 80 years, mean age 62,3+/-0,7), in dosage 120 mg 3 times daily during 3 months in addition to somatic therapy. A patient's state was assessed before, during and after the treatment using clinical methods and a battery of psychometric scales and neuropsychological tests. A significant improvement of neurological and mental status was found in 90 (90%) of patients that was most distinctly observed in the dynamics of their global state and neurocognitive performance on the MMSE and other tests. The effect of the drug was less pronounced for affective disorders - depression and anxiety. The drug was well-tolerated by patients.