Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388)

RATIONALE: The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. HYPOTHESIS: Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. SAMPLE SIZE ESTIMATES: The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. METHODS AND DESIGN: Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. STUDY OUTCOME: The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). DISCUSSION: The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack

Baseline characteristics of the 3,096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke' (TARDIS) trial

Background: The risk of recurrence following ischaemic stroke (IS) or transient ischaemic attack (TIA) is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design: The Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial was an international multicentre prospective randomised open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute IS or TIA. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life) and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviation, SD). Results: Recruitment ran from April 2009 to March 2016. 3,096 patients were recruited from 106 sites in 4 countries (Denmark 1.6%, Georgia 2.7%, New Zealand 0.2%, UK 95.4%). Randomisation characteristics included: age 69.0 (10.1) years; male 1945 (62.8%); time onset to randomisation 29.4 (11.9) hours; stroke severity (National Institutes for Health Stroke Scale) 2.8 (3.6); blood pressure 143.5 (18.2)/79.5 (11.4) mmHg; IS 2143 (69.2%), TIA 953 (30.8%). Conclusion: TARDIS was a large trial of intensive/triple antiplatelet therapy in acute IS and TIA, and included participants from four predominantly Caucasian countries who were representative of patients in many western stroke services

Clinical utility of remote platelet function measurement using P-selectin: assessment of aspirin, clopidogrel, and prasugrel and bleeding disorders

Vascular diseases such as myocardial infarction and ischemic stroke are associated with increased platelet function whilst the risk of recurrence is reduced by antiplatelet agents such as aspirin, clopidogrel, and prasugrel. However, some patients exhibit high platelet reactivity, especially with clopidogrel. Existing platelet function tests may not be ideal in that they can be expensive, are often time consuming, and measurements must be made near to the patient and within a few hours of blood collection. Platelet activation leads to translocation of P-selectin from alpha-granules to the cell surface. Following activation with arachidonic acid (which is blocked by aspirin) or adenosine diphosphate (inhibited by clopidogrel) and fixation, samples may be stored or posted to a laboratory performing flow cytometric quantification of platelet P-selectin expression. Acute myocardial infarction and ischemic stroke are associated with high platelet reactivity on clopidogrel in 6–58% of patients when assessed with P-selectin expression, and high reactivity was associated with an increased risk of recurrence after myocardial infarction. Use of P-selectin expression tests may also be of relevance to surgical and veterinary practice and the diagnosis of mild bleeding disorders. The present review explores this topic in further detail

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Стадії провадження у справах за зверненнями громадян

Берідзе, М. Н. Стадії провадження у справах за зверненнями громадян / М. Н. Берідзе // Вісник Національного університету внутрішніх справ. - 2005. - Вип. - 29. - С. 139-147.Розглянуто стадії провадження у справах за зверненнями громадян. Рассмотрены стадии производства по обращениям граждан. The stages of proceedings in cases of citizens' applications are considered

Особливості провадження за зверненнями громадян

Берідзе, М. Н. Особливості провадження за зверненнями громадян / М. Н. Берідзе // Вісник Національного університету внутрішніх справ. - 2003. – Вип. 24. - С. 77-80Проаналізовані суспільні відносини, які пов’язані з порушеннями посадовими особами прав і свобод громадян, подання останніми скарги в адміністративний або судовий орган, регулюються нормами права адміністративної юстиції. Норми, які включаються в право адміністративної юстиції, потребують наукового осмислення. Проанализированы общественные отношения, связанные с нарушениями должностными лицами прав и свобод граждан, предоставление последними жалобы в административный или судебный орган, регулируются нормами права административной юстиции. Нормы, которые включаются в право административной юстиции, требуют научного осмысления. The public relations related to violations by citizens of the rights and freedoms of citizens, the submission of complaints by the latter to an administrative or judicial body, are regulated by the norms of administrative justice. The norms that are included in the law of administrative justice require scientific understanding

Plastid DNA sequence diversity in wild grapevine samples (Vitis vinifera subsp. sylvestris) from the Caucasus region

DNA sequence diversity was investigated in three plastid regions (the trnH-psbA intergenic spacer, accDpsaI intergenic spacer and the rpl16 intron) in a group of 40 wild grape (Vitis vinifera subsp. sylvestris) samples from the South Caucasus. This group included 22 samples from Georgia, 9 samples from Azerbaijan, 2 samples from Armenia and 7 samples from Turkey. The South Caucasus region is widely believed to be the area in which grape domestication began, and the study of genetic diversity in this region is viewed as key to understanding grape domestication in general. Four plastid haplotypes are evident in the 40 samples, and are designated by their character states at each of the 4 polymorphic positions: AAAT – 22 samples, ATTT – 6 samples, GTAC – 1 sample, and ATAT – 11 samples. The AAAT haplotype is restricted to Georgia and Azerbaijan, the ATAT haplotype is distributed across the entire study area, the ATTT haplotype is distributed in the southern part of the study area from the Black Sea to the Caspian Sea. The single GTAC haplotype was only found in southwestern Georgia. The AAAT haplotype is restricted to both wild (V. vinifera subsp. sylvestris) and cultivated (V. vinifera subsp. vinifera) grape samples from the Caucasus. This observation and the presence of all other plastid haplotypes observed in a previous study of worldwide grape cultivars highlight both unique and high levels of genetic variation in wild grape (V. vinifera subsp. sylvestris) from the greater Caucasus region.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Peculiarities of the relationship to disease and level of anxiety in children under treatment in the stationary conditions

The article describes the types of attitudes of children under treatment in the cardiological, gastroenterological and nephrology departments to the disease, assessed their levels of anxiety, revealed and justified the relationship between the attitude to the disease and anxietyВ статье рассмотрены типы отношения детей, находящихся на лечении в кардиологическом, гастроэнтерологическом и нефрологическом отделениях, к болезни, оценены уровни их тревожности, выявлена и обоснована взаимосвязь между отношением к болезни и тревожностью