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      Tissue plasminogen activator; identifying major barriers related to intravenous injection in ischemic acute cerebral infraction

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          Abstract

          Background:

          According to previous publications, in patients with acute ischemic cerebral infarction, thrombolytic therapy using intravenous tissue plasminogen activator (IV-tPA) necessitates precise documentation of symptoms’ onset. The aim of this study was to identify major barriers related to the IV-tPA injection in such patients.

          Materials and Methods:

          Between the year 2014-2015, patients with definitive diagnosis of acute cerebral infarction ( n = 180) who attended the neurology ward located at the Isfahan Alzahra Hospital were studied. To investigate barriers related to door to IV-tPA needle time, personal reasons, and criteria for inclusion or exclusion of patients, three questionnaire forms were designed based on the Food and Drug Administration-approved indications or contraindications.

          Results:

          The mean age of males versus females was 60 versus 77.5 years (ranged 23–93 vs. 29–70 years), respectively. Out of total population, only 10.7% transferred to hospital in <4.5 h after the onset of symptoms. Regarding to eligibility for IV-tPA, 68.9% of total population have had criteria for such treatment. Concerning to both items such as transferring to hospital in <4.5 h after the onset of symptoms and eligibility for IV-tPA, only 6.6% of total population met the criteria for such management. There was ignorance or inattention to symptoms in 75% of population studied. There was a mean of 195.92 ± 6.65 min (182.8–209.04 min) for door to IV-tPA needle time.

          Conclusion:

          Despite the international guidelines for IV-tPA injection within 3–4.5 h of ischemic stroke symptoms’ onset, the results of this study revealed that falling time due to ignorance of symptoms, literacy, and living alone might need further attention. As a result, to decrease death and disability, educational programs related to the symptoms’ onset by consultant neurologist in Isfahan/Iran seem to be advantageous.

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          Most cited references26

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          Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis

          Summary Background Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an updated systematic review and meta-analysis. Methods We searched for randomised trials of intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6 h after stroke. Findings In up to 12 trials (7012 patients), rt-PA given within 6 h of stroke significantly increased the odds of being alive and independent (modified Rankin Scale, mRS 0–2) at final follow-up (1611/3483 [46·3%] vs 1434/3404 [42·1%], OR 1·17, 95% CI 1·06–1·29; p=0·001), absolute increase of 42 (19–66) per 1000 people treated, and favourable outcome (mRS 0–1) absolute increase of 55 (95% CI 33–77) per 1000. The benefit of rt-PA was greatest in patients treated within 3 h (mRS 0–2, 365/896 [40·7%] vs 280/883 [31·7%], 1·53, 1·26–1·86, p<0·0001), absolute benefit of 90 (46–135) per 1000 people treated, and mRS 0–1 (283/896 [31·6%] vs 202/883 [22·9%], 1·61, 1·30–1·90; p<0·0001), absolute benefit 87 (46–128) per 1000 treated. Numbers of deaths within 7 days were increased (250/2807 [8·9%] vs 174/2728 [6·4%], 1·44, 1·18–1·76; p=0·0003), but by final follow-up the excess was no longer significant (679/3548 [19·1%] vs 640/3464 [18·5%], 1·06, 0·94–1·20; p=0·33). Symptomatic intracranial haemorrhage (272/3548 [7·7%] vs 63/3463 [1·8%], 3·72, 2·98–4·64; p<0·0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefit to those aged 80 years or younger, particularly when treated early. Interpretation The evidence indicates that intravenous rt-PA increased the proportion of patients who were alive with favourable outcome and alive and independent at final follow-up. The data strengthen previous evidence to treat patients as early as possible after acute ischaemic stroke, although some patients might benefit up to 6 h after stroke. Funding UK Medical Research Council, Stroke Association, University of Edinburgh, National Health Service Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute, Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo University Hospital.
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            Stroke Prognostication using Age and NIH Stroke Scale: SPAN-100.

            Age and stroke severity are major determinants of stroke outcomes, but systematically incorporating these prognosticators in the routine practice of acute ischemic stroke can be challenging. We evaluated the effect of an index combining age and stroke severity on response to IV tissue plasminogen activator (tPA) among patients in the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke trials. We created the Stroke Prognostication using Age and NIH Stroke Scale (SPAN) index by combining age in years plus NIH Stroke Scale (NIHSS) ≥100. We applied the SPAN-100 index to patients in the NINDS tPA stroke trials (parts I and II) to evaluate its ability to predict clinical response and risk of intracerebral hemorrhage (ICH) after thrombolysis. The main outcome measures included ICH (any type) and a composite favorable outcome (defined as a modified Rankin Scale score of 0 or 1, NIHSS ≤1, Barthel index ≥95, and Glasgow Outcome Scale score of 1) at 3 months. Bivariate and multivariable logistic regression analyses were used to determine the association between SPAN-100 and outcomes of interest. Among 624 patients in the NINDS trials, 62 (9.9%) participants were SPAN-100 positive. Among those receiving tPA, ICH rates were higher for SPAN-100-positive patients (42% vs 12% in SPAN-100-negative patients; p < 0.001); similarly, ICH rates were higher in SPAN-100-positive patients (19% vs 5%; p = 0.005) among those not receiving tPA. SPAN-100 was associated with worse outcomes. The benefit of tPA, defined as favorable composite outcome at 3 months, was present in SPAN-100-negative patients (55.4% vs 40.2%; p < 0.001), but not in SPAN-100-positive patients (5.6% tPA vs 3.9%; p = 0.76). Similar trends were found for secondary outcomes (e.g., symptomatic ICH, catastrophic outcome, discharge home). The SPAN-100 index could be a simple method for estimating the clinical response and risk of hemorrhagic complications after tPA for acute ischemic stroke. These results need further confirmation in larger contemporary datasets.
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              Epidemiology of stroke and transient ischemic attacks: Current knowledge and perspectives.

              Because of the growing size and aging of the world's population, the global burden of stroke is increasing dramatically. Current epidemiological data indicate that 16.9 million people suffer a stroke each year, which represents a global incidence of 258/100,000/year, with marked differences between high- and low-income countries, and an age-adjusted incidence 1.5 times higher in men than in women. Although primary prevention has contributed to a decrease in stroke incidence in high-income countries, the so-called 'epidemiological transition' has led to an increase in incidence in middle-to-low-income countries as well. In addition, the incidence of ischemic stroke in young adults is on the rise, suggesting a need for specific preventative interventions in that age group. The number of stroke survivors almost doubled between 1990 and 2010, and has now reached 33 million people. According to epidemiological projections, this number will rise to 77 million by 2030. In France, the number of hospitalizations for an acute cerebrovascular event was about 138,000 in 2009, accounting for 3% of the total national health expenditure. Outcomes after stroke are frequently impaired by complications, including motor handicaps, dementia, depression, fatigue, and a high risk of early rehospitalization and institutionalization, with adverse consequences in terms of socioeconomic costs. In addition, there are 5.9 million stroke-related deaths worldwide every year. Finally, although many analytical epidemiological studies have considerably increased our knowledge of risk factors for stroke, the recent INTERSTROKE study provided evidence that 10 risk factors alone accounted for 88% of all strokes. Many of these risk factors are modifiable, which suggests that efforts should be made to promote interventions that aim to reduce the risk of stroke. A new 'mass approach' aiming to reduce the level of stroke risk factors in all people in a region, regardless of any given individual's level of risk, is currently still being developed. This interesting and innovative way to spread stroke awareness is based on the use of an internationally validated mobile-phone application that can calculate the risk of stroke for any given individual, and also contains a section to educate people on stroke warning symptoms and signs.
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                Author and article information

                Journal
                J Res Med Sci
                J Res Med Sci
                JRMS
                Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences
                Medknow Publications & Media Pvt Ltd (India )
                1735-1995
                1735-7136
                2017
                16 February 2017
                : 22
                : 19
                Affiliations
                [1 ]Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
                [2 ]Isfahan Neuroscience Research Centre, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
                [3 ]Isfahan Kidney Transplantation Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
                Author notes
                Address for correspondence: Dr. Zahra Tolou-Ghamari, Isfahan Kidney Transplantation Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail: toloeghamari@ 123456pharm.mui.ac.ir
                Article
                JRMS-22-19
                10.4103/1735-1995.200318
                5367212
                e66c696e-2c50-4856-ae75-5ef3d807f51e
                Copyright: © 2017 Journal of Research in Medical Sciences

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 10 February 2016
                : 16 July 2016
                : 23 November 2016
                Categories
                Original Article

                Medicine
                cerebral infarction,injection barriers,ischemic stroke,tissue plasminogen activator
                Medicine
                cerebral infarction, injection barriers, ischemic stroke, tissue plasminogen activator

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