State of functional systems in patients with ischemic stroke

The purpose of this work is to study features of the ranking of functional systems in patients with ischemic stroke for better understanding of the integrative processes occurring in the body of the patient during dysfunction of cerebral circulation. The study involved 50 patients with acute MRI-verified hemispheric ischemic stroke, mean age 62,0 ± 6,5 years. NIHSS, Barthel and Rankin Scales were used to assess the dynamics of neurological deficit. Changes in vegetative homeostasis were investigated using short recordings of heart rate variability. Hamilton and Spielberger-Hanin questionnaires were used to identify anxiety and depressive disorders. The results were interpreted in the context of the theory of P.K. Anokhin of functional systems in accordance with the metabolic, homeostatic, behavioral, mental and social level of organization of functional systems. According to the study, it was found that 26% of patients on days 2-4 of development of ischemic stroke (IS) noted raising the temperature to 37 ± 0,46. In the study of vegetative homeostasis showed an increase in the proportion of very low frequency in the general spectrum of heart rate variability, which indicates a strengthening of humoral regulation (index VLF (Very Low Frequency) - 755 ±101,6 on the 3rd day and 657 +108,5 - on the 15th day). We have established the fact in the development of acute ischemic stroke that the activity of functional systems (FS) at the behavioral level of organization is effectively replaced by the medical staff and caregivers out of the violations of patients' self-help skills (Barthel Index: 42,0+6,74 on 3rd day and 67,5 ± 7,54 - on the 15th day; Rankin Scale: 3,6+0,51 on 3rd day and 3,0+0,81 - on the 15th day). When analyzing the activity of FS on the mental level of the organization, it was found that the level of anxiety and depressive disorders was directly dependent on the level of neurological deficit. All findings demonstrate the need for an integrative understanding of processes in the patient's body to design optimal treatment and rehabilitation programs.Цель настоящей работы - изучить особенности иерархии функциональных систем у больных с ишемическим инсультом, поскольку при развитии острого нарушения мозгового (ОНМК) необходимо интегративное осмысление процессов, происходящих в организме пациента. В исследовании приняли участие 50 пациентов в остром периоде МРТ-верифицированного полушарного ишемического инсульта (ИИ), средний возраст 62,0±6,5 года. Для оценки динамики неврологического дефицита использовались шкалы NIHSS, Бартел и Рэнкин. Изменения вегетативного гомеостаза исследовались по коротким записям вариабельности ритма сердца. Для выявления тревожно-депрессивных расстройств использовались опросники Гамильтона и Спилбергера-Ханина. Полученные данные были интерпретированы в контексте теории П.К. Анохина о функциональных системах в соответствии с метаболическим, гомеостатическим, поведенческим, психическим и социальным уровнем организации ФС. По результатам исследования было установлено, что у 26% пациентов на 2-4 сутки от развития ИИ отмечалось повышение температуры до 37±0,46. При исследовании вегетативного гомеостаза было выявлено увеличение удельного веса очень низких частот в общем спектре вариабельности ритма сердца, что указывает на усиление гуморальной регуляции (показатель VLF (Very Low Frequency) - 755+101,6 на третий и 657+108,5 - на 15й день). Нами был установлен тот факт, при развитии ОНМК деятельность ФС на поведенческом уровне организации фактически замещается медперсоналом и ухаживающими из-за нарушения у пациентов навыков самообслуживания (индекс Вартел: 42,0+6,74 на 3 день и 67,5+7,54 - на 15й; шкала Ранкина: 3,6+0,51 на 3 день и 3,0+0,81). При анализе деятельности ФС на психическом уровне организации было выяснено, что уровень тревожно-депрессивных расстройств имел прямую зависимость от уровня неврологического дефицита. Все полученные данные демонстрируют необходимость интегративного осмысления процессов в организме пациента для составления оптимальной программы лечения и реабилитации

Levodopa-carbidopa intestinal gel in the treatment of patients with parkinson disease: Results of a 12-month open study

© 2017, Media Sphera. All rights reserved.Objective: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. Material and methods: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of “off” periods, “on” periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient’s diaries) were assessed throughout the whole study. Results: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of “off” periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of “on” periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of “on” periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. Conclusion: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction

Терапия остеоартрита коленных суставов с точки зрения доказательной медицины: ожидаемые краткосрочные, среднесрочные и долгосрочные результаты применения рецептурного кристаллического глюкозамина сульфата

The need for effective drugs for the treatment of knee osteoarthritis (OA) is constantly growing. Current guidelines recommend the use of symptomatic slow acting drugs for osteoarthritis (SYSADOA) such as glucosamine (GCA) in this disease. Among various drugs containing GCA, high bioavailability and clinical efficacy have been shown only for prescription crystalline GCA sulfate (pGCAS) administration. Several meta-analyses and network meta-analyses have shown that efficacy of pGCAS 1500 mg once daily is superior to other GCA-based products (such as GCA hydrochloride with or without sodium sulfate) and the combination of GCA with chondroitin sulfate (CS) in terms of reducing the intensity of pain and improving the functional state. These studies confirmed the favorable safety profile of pGCAS, which was comparable to placebo in the incidence of adverse events. Pharmacoeconomic studies have also demonstrated greater cost-effectiveness of pGCAS compared to other GCA drugs.A group of Russian experts at a meeting of the advisory committee reviewed the evidence in favor of the use of pGCAS and evidence of its effectiveness in the treatment of knee OA in comparison with other products that include GCA, and the fixed combination of GCA with CS. Taking into account the results obtained, the use of pGCAS at a dose of 1500 mg once a day is recommended as a rational choice for the treatment of knee OA.Потребность в эффективных препаратах для терапии остеоартрита (ОА) коленных суставов (КС) постоянно растает. В современных руководствах рекомендуется применять при этом заболевании симптоматические средства замедленного действия (SYSADOA), такие как глюкозамин (ГКА). Среди различных лекарственных средств, содержащих ГКА, высокая биодоступность и клиническая эффективность доказаны только для рецептурного кристаллического ГКА сульфата (рГКАС). В нескольких метаанализах и сетевых метаанализах было показано, что рГКАС в дозе 1500 мг 1 раз в сутки превосходит по эффективности другие продукты на основе ГКА (такие как ГКА гидрохлорид с натрия сульфатом или без него) и комбинации ГКА с хондроитина сульфатом (ХС) с точки зрения снижения интенсивности боли и улучшения функционального состояния. В этих исследованиях был подтвержден благоприятный профиль безопасности рГКАС, который по частоте развития нежелательных явлений был сопоставим с плацебо. Фармакоэкономические исследования также продемонстрировали большую экономическую эффективность рГКАС по сравнению с другими лекарственными средствами ГКА.Группа российских экспертов на совещании консультативного комитета рассмотрела свидетельства в пользу применения рГКАС и доказательства его эффективности при лечении ОА КС в сравнении с другими продуктами, в состав которых входит ГКА, и фиксированной комбинации ГКА с ХС. С учетом полученных результатов использование рГКАС в дозе 1500 мг 1 раз в сутки рекомендовано в качестве рационального выбора для лечения ОА КС

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362