Совершенствование механизмов формирования доходов бюджета АРК

Целью нашей работы является исследование механизмов формирования доходов бюджета Автономной Республики Крым и разработка мероприятий по их совершенствованию

Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

Does a carpal tunnel syndrome predict an underlying disease?

Carpal tunnel syndrome (CTS) may be the presenting symptom of an underlying disease such as diabetes mellitus, hypothyroidism or connective tissue disease (CTD). It was investigated whether additional blood tests (glucose level, thyroid‐stimulating hormone level and erythrocyte sedimentation rate) are useful to detect diabetes mellitus, hypothyroidism or CTD in patients with CTS who have not been diagnosed with these diseases before. A group of 516 consecutive patients electromyographically diagnosed with CTS without known diabetes mellitus, hypothyroidism or CTD underwent blood tests and were followed up for incident diabetes mellitus, hypothyroidism or CTD to investigate whether these additional blood tests are useful to detect these diseases in patients with CTS. In our CTS population, only two patients were newly diagnosed with diabetes mellitus, two with hypothyroidism and none with CTD. In general, systematic screening for incident diabetes mellitus, hypothyroidism and CTD through additional blood tests seems to be of little additional value in otherwise typical cases of CTS

Update on the Preventive Antibiotics in Stroke Study (PASS): a randomised controlled phase 3 clinical trial

Stroke is a leading cause of death worldwide. Infections after stroke occur in 30% of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections. To date, 2,470 patients have been included in PASS. Median stroke severity of the first 2,133 patients (second interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the initial trial protocol we proposed a dichotomisation of the mRS as primary analysis of outcome and ordinal regression analysis as secondary analysis of primary outcome, requiring a sample size of 3,200 patients. However, ordinal analysis of outcome data is becoming increasingly more common in acute stroke trials, as it increases statistical power. For PASS, funding is insufficient for inclusion of 3,200 patients with the overall inclusion rate of 15 patients per week. Therefore we change the analysis of our primary outcome from dichotomisation to ordinal regression analysis on the mRS. Power analysis showed that with similar assumptions 2,550 patients are needed using ordinal regression analysis. We expect to complete follow-up in June 2014. A full statistical analysis plan will be submitted for publication before treatment allocation will be unblinded. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection. In this update, we changed our primary outcome analysis from dichotomisation to ordinal regression analysis. Current controlled trials; ISRCTN66140176. Date of registration: 6 April 201

TRIALS UPDATE Open Access Update on the Preventive Antibiotics in Stroke

and Diederik van de Beek 1,4† Background: Stroke is a leading cause of death worldwide. Infections after stroke occur in 30 % of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections. Results: To date, 2,470 patients have been included in PASS. Median stroke severity of the first 2,133 patients (second interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the initial trial protocol we proposed a dichotomisation of the mRS as primary analysis of outcome and ordinal regression analysis as secondary analysis of primary outcome, requiring a sample size of 3,200 patients. However, ordinal analysis of outcome data is becoming increasingly more common in acute strok

Preventive Antibiotics for Infections in Acute Stroke A Systematic Review and Meta-analysis

Objective: To provide a systematic overview and meta-analysis of randomized clinical trials evaluating preventive antibiotics in patients with acute stroke. Data Sources: The MEDLINE (1966-February 2009) and Cochrane databases and reference lists of retrieved articles. Study Selection: Randomized controlled trials on preventive antibiotic treatment in stroke. For inclusion, at least case fatality or infection rate had to be recorded. Data Extraction: Each study was scored for methodological key issues and appraised by the Jadad scale. We extracted the data using a predetermined protocol and included all patients who were randomized or who started therapy in an intent-to-treat analysis. Data Synthesis: We identified 4 randomized clinical trials including 426 patients; 94% had ischemic stroke. Study interventions were fluoroquinolones in 2 and tetracycline or a combination of beta-lactam antibiotic with beta-lactamase inhibitor in 1. Therapy was started within 24 hours of stroke onset. Duration of therapy varied between 3 and 5 days. The methodological quality ranged from 2 to 5 on the Jadad scale, and studies were subject to potential bias. The proportion of patients with infection was significantly smaller in the antibiotic group than in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients). The pooled odds ratio for infection was 0.44 (95% confidence interval, 0.23-0.86). Ten of 210 patients (4.8%) in the antibiotic group died, compared with 13 of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality was 0.63 (95% confidence interval, 0.22-1.78). No major harm or toxicity was reported. Conclusions: In adults with acute stroke, preventive antibiotics reduced the risk of infection, but did not reduce mortality. The observed effect warrants evaluation of preventive antibiotics in large stroke trial

Stroke-associated infection is an independent risk factor for poor outcome after acute ischemic stroke: data from the Netherlands Stroke Survey

BACKGROUND: Infections are a common and serious threat to patients with acute ischemic stroke. The aim of this study was to assess the effect of infection on mortality and functional outcome at discharge and at 1 year. METHODS: From a consecutive cohort study in 11 centers, the Netherlands Stroke Survey, we selected 521 patients with ischemic stroke admitted to hospital within 48 h of onset. Stroke-associated infection was defined as infection occurring within 7 days after admission. Poor outcome (modified Rankin score >2) was recorded at discharge and at 1 year. RESULTS: Stroke-associated infection occurred in 78 patients (15%); 39 of these (7.5%) had pneumonia and 23 (4.4%) had urinary tract infection. Overall, 276 patients (53%) had a poor outcome at 1 year. Poor outcome was recorded in 69 patients with stroke-associated infection (88%), and 37 of the 78 patients with stroke-associated infection (47%) had died at 1 year. After adjustment for confounders, stroke-associated infection was associated with poor outcome at discharge [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.0-6.7] and at 1 year (OR 3.8, 95% CI 1.8-8.9). Pneumonia had a stronger association with poor outcome at 1 year (OR 10, 95% CI 2.2-46). CONCLUSIONS: This study suggests that stroke-associated infection, in particular pneumonia, is independently associated with poor functional outcome after ischemic strok

Preventive Antibiotics in Stroke Study: Rationale and Protocol for a Randomised Trial

Rationale Stroke is a leading cause of death worldwide. Fever after stroke is a strong predictor of a poor outcome. Infections occur in up to 40% of patients with stroke and have also been associated with poor outcomes. Preventive antibiotic therapy lowers the infection rates in patients after stroke, as shown in a recent meta-analysis of randomised studies. Phase III trials evaluating the effect of antibiotic prophylaxis on clinical outcomes in sufficient numbers of patients with stroke have, however, not been performed to date. Ceftriaxone, an off-patent medicine, is an antibiotic with a broad defence against the bacteria that cause the most common infections after stroke. Preventive antibiotic therapy with ceftriaxone may potentially reduce poor outcome after acute stroke and, therefore, a randomised clinical trial is warranted. Aim The aim of the present study is to investigate whether the preventive use of the antibiotic ceftriaxone improves functional outcome in patients with stroke. Design We will conduct a multicentre prospective, randomised, open-label, blinded end point trial of standard care with preventive ceftriaxone treatment and compare it with standard care without preventive ceftriaxone. Study Adult patients with stroke (both ischaemic and haemorrhagic) and a score >= 1 on the National Institutes of Health Stroke Scale will be included. The 3200 patients will be randomly assigned to two groups of 1600 patients. One group will receive standard care and ceftriaxone at a dose of 2 g, given every 24 h intravenously for four-days, and the other group will receive stroke-unit care without preventive antibiotic treatment. Outcomes The primary end point will be functional outcome at a three-month follow-up on the modified Rankin Scale, dichotomised as a favourable outcome (0-2) or an unfavourable outcome (3-6). Secondary outcome measures will be death rate at discharge and three-months, infection rate during hospital admission, length of hospital admission, volume of poststroke care, use of antibiotics during the three-month follow-up, functional outcome using the full ordinal scoring range of the modified Rankin Scale, quality-adjusted life years and cost

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial

Background and Purpose—Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. Methods—PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Results—Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74–1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Conclusions—Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed