Анализ объемов потребления психотропных лекарственных средств, применяемых для лечения шизофрении, в стационарах различного типа

the goal of our research was to carry out an analysis of psychotropic drug utilization used for patients with schizophrenia in two (state and municipal) in-patient clinics during 2000 and 2010, using the DDD methodology. As the result, we found out that psychotropic drug utilization increased from 2000 to 2010 in both types of in-patient clinics. Consumption of second-generation antipsychotics increase in state clinic in 2010. And in the state clinic we can observe a favorable trend in the decrease of antidepressants and tranquilizers consumption.открытое фармакоэпидемиологическое ретроспективное исследование потребления психотропных лекарственных средств, применяемых для лечения шизофрении, проводилось в 2000-2010 гг. Цель: целью данного исследования было проведение анализа объемов потребления психотропных лекарственных средств (ЛС), применявшихся для лечения параноидной шизофрении в двух стационарах разного типа в 2000 и 2010 гг. с помощью методики «определенных дневных доз». Материалы и методы: оценивались демографические данные пациентов, диагноз, синдром, тип течения заболевания, длительность госпитализации, возраст начала заболевания; названия нейролептиков (НЛ) и препаратов сопутствующей терапии с указанием режима их применения (доза, кратность, путь введения), с использованием методики «определенных дневных доз» (Defined Daily Doses – DDD). Также оценивались побочные эффекты психофармакотерапии и исход лечения. Результаты: обнаружено, что объемы потребления психотропных ЛС при стационарном лечении шизофрении выросли с 2000 по 2010 г., независимо от типа стационара. Объемы использования атипичных НЛ в 2010 г. выросли при снижении объемов потребления антидепрессантов и транквилизаторов

Анализ структуры затрат на фармакотерапию инфаркта мозга в стационаре в 2009-2011 гг

Pharmacoeconomic analysis includes the assessment of direct cost structure in pharmacotherapy of cerebral infarction for the period of 2009-2011 in healthcare institutions in Saratov (762 patients) based on ABC analysis and frequency analysis. The results of the mentioned analysis showed the presence of drugs without proven efficacy and a very high associated cost component (75.67%) of purchasing budget in drug group «A». It was revealed, that the drugs of scientifically substantiated efficacy and safety are not used sufficiently in treatment of cerebral infarction. On the other hand the drugs without proven efficacy are widely used, which leads to an increase in financial losses of the state and population. The results of clinical and economic analysis showed the need for changing the cost structure for drug therapy of the mentioned disease in hospitals.Фармакоэкономический анализ включал оценку структуры прямых затрат на фармакотерапию инфаркта мозга в 2009-2011 годах в стационарных лечебных учреждениях г. Саратова (762 пациента) с использованием АВС- и частотного анализа. По результатам этого анализа было выявлено наличие в группе «А» лекарственных препаратов без доказанной эффективности и очень высокая доля затрат на них (75,67%) от бюджета закупок. Отмечено недостаточное применение лекарственных средств, применяемых при лечении инфаркта мозга и имеющих научно обоснованные доказательства эффективности и безопасности. Напротив, широкое распространение получило применение препаратов без доказанной эффективности, что приводит к увеличению финансовых потерь государства и населения. Результаты проведенного клинико-экономического анализа показали необходимость изменения структуры затрат на фармакотерапию данного заболевания в стационарах города

Результаты клинического исследования препаратов Траумель® С и Цель® Т у пациентов с остеоартритом коленного сустава, имеющих сопутствующие сердечно-сосудистые заболевания

   Objective: to evaluate the efficacy and safety of simultaneous intramuscular administration of Traumeel® S and Zeel® T followed by therapy with the tablet medication Zeel® T in patients with knee osteoarthritis (OA) and concomitant cardiovascular diseases.   Material and methods. The analysis included 119 patients aged 45–79 years (78.2 % women and 21.8 % men) with confirmed diagnosis of knee OA according to Altman criteria, stage II–III according to Kellgren–Lawrence and confirmed cardiovascular disease. The main indicator of efficacy was the change in pain intensity in the target knee joint according to the “Pain” subscale of the WOMAC questionnaire (A) at the final examination compared to the baseline. Other criteria were the dynamics of each symptom of knee OA according to the WOMAC questionnaire (pain, stiffness, and functional impairment, total score) on each visit, pain intensity in the target joint on a visual analogue scale (VAS), time it takes to travel 15 m, and the patient's overall disease assessment on the VAS. In addition, duration of use and dose of paracetamol (if used) were assessed, as well as quality of life by EuroQol and adverse events (AEs). Treatment safety was also analyzed in patients who had received at least one dose of the study drug.   Results and discussion. WOMAC pain intensity decreased by on average of 3.8 points: from 7.6 to 3.8 points (95 % confidence interval, CI from -4.3 to -3.3). Data on changes in knee OA symptoms (pain, stiffness, and functional impairment) for each WOMAC subscale and the total score showed significant improvement at each follow-up visit (p < 0.0001). The VAS pain level decreased by 52%. An improvement in joint function was noted: the time it takes to travel 15 m fell from 19.5 to 16.4 s (p < 0.0001). The EuroQol quality of life score also improved from 57.1 ± 16.2 points at baseline to 71.1 ± 14.8 points on the 84<sup>th</sup> day of therapy. Thirty (25.2 %) patients had AEs, mainly neurological: headache (7.6 %) and hypoesthesia (1.7 %). No serious AEs were recorded. An association between AEs and study drug use was noted in 4 patients (headache, hypoesthesia, muscle cramps, and injection site pain).   Conclusion. The results of the study confirm the efficacy and safety of the use of Traumeel® S and Zeel® T in patients with knee OA who have concomitant cardiovascular disease. During therapy, a significant decrease in pain and other clinical signs of OA (stiffness, limitation of physical activity) was observed, which allows us to recommend this treatment regimen for patients with comorbid pathology, as well as with the risk of developing of AEs during non-steroidal anti-inflammatory drugs therapy.   Цель исследования – оценить эффективность и безопасность совместного внутримышечного введения Траумель® С и Цель® Т с последующей терапией таблетированным препаратом Цель® Т у пациентов с остеоартритом (ОА) коленного сустава (КС), имеющих сопутствующие сердечно-сосудистые заболевания.   Материал и методы. В анализ включено 119 пациентов 45–79 лет (78,2 % женщин и 21,8 % мужчин) с подтвержденным диагнозом ОА КС по критериям Альтмана, II–III стадией по Kellgren–Lawrence и подтвержденным заболеванием сердечно-сосудистой системы. Основным критерием эффективности было изменение интенсивности боли в целевом КС по субшкале «Боль» опросника WOMAC (A) на завершающем визите по сравнению с исходным уровнем, а дополнительными – динамика отдельных симптомов ОА КС по опроснику WOMAC (боль, скованность и функциональная недостаточность, суммарный индекс) при каждом визите, интенсивность боли в целевом КС по визуальной аналоговой шкале (ВАШ), время прохождения 15 м и общая оценка заболевания пациентом по ВАШ. Кроме того, оценивались продолжительность приема и доза парацетамола (если он использовался), а также качество жизни по EuroQol и нежелательные явления (НЯ). Проведен также анализ безопасности терапии у пациентов, получивших хотя бы одну дозу исследуемого препарата.   Результаты и обсуждение. Интенсивность боли по WOMAC снизилась в среднем на 3,8 балла: с 7,6 до 3,8 балла (95 % доверительный интервал, ДИ от -4,3 до -3,3). Данные об изменении симптомов ОА КС (боль, скованность и функциональная недостаточность) по каждой подшкале WOMAC и суммарный индекс свидетельствовали о значимом улучшении (p < 0,0001) при каждом последующем визите. Уровень боли по ВАШ уменьшился на 52 %. Отмечено улучшение функциональной способности суставов: изменение времени прохождения 15 м (p < 0,0001) с 19,5 до 16,4 с. Оценка качества жизни по EuroQol также улучшилась с 57,1 ± 16,2 балла исходно до 71,1 ± 14,8 балла на 84-й день терапии. У 30 (25,2 %) пациентов возникли НЯ, в основном со стороны нервной системы: головная боль (7,6 %) и гипестезия (1,7 %). Серьезных НЯ не зарегистрировано. Связь НЯ с приемом исследуемого препарата выявлена у 4 пациентов (головная боль, гипестезия, мышечные спазмы и боль в месте инъекции).   Заключение. Результаты исследования подтвердили эффективность и безопасность применения препаратов Траумель® С и Цель® Т у пациентов с ОА КС, имеющих сопутствующие сердечно-сосудистые заболевания. На фоне терапии отмечено значимое уменьшение боли и других клинических признаков ОА (скованности, ограничения физической активности), что позволяет рекомендовать данную схему лечения для пациентов с коморбидной патологией, а также с риском развития НЯ при приеме нестероидных противовоспалительных препаратов

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402