Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Saraswati Dental College
Lucknow
On Sep 2018




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Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : November | Volume : 16 | Issue : 11 | Page : OC11 - OC15 Full Version

Outcome Analysis of Intravenous Thrombolytic Therapy in Patients with Acute Ischaemic Stroke and its Association with Critical Time Intervals: An Ambispective Study


Published: November 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/58866.17037
Syama Viswanath, Susan Tharian, Mathew Pulicken, Sethu Babu

1. Consultant, Department of Emergency Medicine, Thiruvalla Medical Mission, Thiruvalla, Kerala, India. 2. Assistant Professor, Department of Emergency Medicine, Pushpagri Institute of Medical Sciences, Thiruvalla, Kerala, India. 3. Associate Professor, Department of Critical Care, Pushpagri Institute of Medical Sciences, Thiruvalla, Kerala, India. 4. Associate Professor, Department of Emergency Medicine, Pushpagri Institute of Medical Sciences, Thiruvalla, Kerala, India.

Correspondence Address :
Dr. Sethu Babu,
Associate Professor, Department of Emergency Medicine, Pushpagiri Institute of
Medical Sciences, Thiruvalla-689101, Kerala, India.
E-mail: sethubabuchest@gmail.com

Abstract

Introduction: Intravenous thrombolytic therapy has become the standard of care in patients with acute ischaemic stroke. The success of this therapy depends on achieving the shortest time between the onset of stroke and reperfusion. Many clinical tasks like neurological assessment, imaging and its interpretation, exclusion of contraindications and informed consent must be taken care of, prior to administration of thrombolytic therapy. As this is a time sensitive intervention, it may have variable outcomes in different settings.

Aim: To evaluate the immediate and 90-day neurological outcome of the patients who had received intravenous thrombolytic therapy in acute ischaemic stroke and to evaluate its association with stipulated critical time intervals.

Materials and Methods: This was an ambispective observational study conducted for a period of 18 months (April 2018-October 2019) in the Emergency Department of Pushpagiri Institute of Medical Sciences, Thiruvalla, a tertiary care hospital in central Kerala, India. For the prospective arm of the study, data were collected from the patients who came to the Emergency Department with acute ischaemic stroke in the window period (three hours) or in the extended window period (3-4.5 hours). Onset to door time, door-to-imaging time, door-to-needle time and onset-to-needle time were assessed and recorded. National Institute of Health Stroke Scale (NIHSS) score at presentation and at 24 hours post-thrombolysis was noted. Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) brain report 24 hours post-thrombolysis was followed-up. The functional outcome at 90 days was assessed using Modified Rankin Scale (MRS) score. For the retrospective arm of the study, the relevant data were collected from the hospital records and the patients were followed-up. The association between the stipulated critical time intervals and 24 hours post-thrombolysis NIHSS score, as well as MRS score at 90 days were calculated using the statistical analysis tool STATA v.14. Statistical comparisons were performed between subgroups using the Chi-square (χ2) test, Fischer’s-exact test, Wilcoxon signed-rank test, and Mann-Whitney U-test as indicated for dichotomous or continuous variables. For all statistical analyses, a p-value of <0.05 was taken as statistically significant.

Results: Of the total 110 patients, 105 patients (95.5%) reached the hospital within three hours (window period), and five patients (4.5%) reached within 4.5 hours (extended window period). A total of 58 patients (52.7%) received thrombolytic treatment within three hours and 52 patients (47.3%) within 4.5 hours. After 24 hours of thrombolysis, improvement in neurological function, as defined by an improvement in NIHSS score by 4 or more was found in 73 patients (66.4%). At 90 days follow-up, 76 patients (69.1%) became functionally independent with an MRS score of 0-2. There was a significant association between NIHSS score 24-hours post-thrombolysis and the functional outcome at 90 days. Of the various stipulated critical time intervals, a significant association was seen only with onset-to-door time and NIHSS score 24 hours post-thrombolysis.

Conclusion: A total of 69.1% of the patients who have received intravenous thrombolytic therapy for acute ischaemic stroke in this study have shown favourable functional outcome at 90 days. The NIHSS score 24 hours post-thrombolysis compared to baseline is a good predictor of the neurological outcome at 90 days.

Keywords

Door-to-imaging time, Door-to-needle time, Modified rankin scale, National institute of health stroke scale, Window period

Stroke is the second leading cause of death in adults globally. Ischaemic stroke accounts for about 62.4% of all strokes (1). Acute ischaemic strokes are caused by thrombotic or embolic occlusion of cerebral blood vessels. Thrombolytic therapy has added a new dimension in acute stroke care. When administered early (within 4.5 hours of onset), intravenous thrombolytic therapy with alteplase improves outcome in patients with stroke as shown by the National Institute of Neurological Disorders and Stroke (NINDS) trial (2) and the European Cooperative Acute Stroke Study III (ECASS III) trial (3). However, this is a time sensitive intervention because giving this therapy after the window period is associated with increased risk (4). It is imperative that no time should be wasted from the onset of stroke to thrombolysis. To ensure this, NINDS has established critical in-hospital time goals for the assessment and management of patients with suspected stroke (5),(6). Implementing an Institutional Stroke management protocol is a good strategy to ensure adherence to these time-sensitive clinical goals (7),(8),(9). This requires a well-coordinated plan from Emergency Medicine, Neurology, and Radiology departments with a focus on rapid identification, response and intervention. The real-life implementation of a stroke protocol is fraught with many difficulties. In a developing country like India the challenges may be more pronounced (10). There is limited data from India regarding the implementation of thrombolytic therapy and the challenges involved in adhering to the time sensitive goals and its influence on clinical outcomes. In this context, the aim of the study was to ascertain the outcome of thrombolytic therapy with regard to critical time intervals. The primary objective of the study was to assess the immediate (at 24 hours) and 90 days neurological outcome of the patients who received intravenous thrombolytic therapy for acute ischaemic stroke. The secondary objectives were to find the association between the stipulated critical time intervals namely onset-to-door time, door-to-imaging time, door-to-needle time and onset-to-needle time with the neurological status at 24 hours post- thrombolysis and the functional outcome at 90 days.

Material and Methods

The study was conducted as an ambispective observational study with prospective and retrospective arms. It was conducted in the Department of Emergency Medicine, Pushpagiri Institute of Medical Sciences, Thiruvalla, Kerala, India. The study was conducted for a period of 18 months from April 2018-October 2019. The study protocol was approved by the Institutional Ethics committee (PIMSRC/E1/388A/11/2018).

Inclusion criteria: Patients in the age group between 18-90 years with acute ischaemic stroke who were eligible (6) for thrombolysis were included in the study.

Exclusion criteria: Patients with symptom duration more than four and half hours (past window period), those with contraindications (6) for thrombolytic treatment, patients <18 years or >90 years old, patients whose data were not available (in case of retrospective study), and patients not consenting to the study were excluded from the study.

Sample size calculation: Sample size was calculated assuming the confidence interval of 95%, proportion of outcome as 78.5% (11) and error as 10% of P, using the formula:

Total sample size was calculated as 110. For the prospective arm of the study, informed consent was taken from the patient or the legally authorised representative if the patient was not able to give consent. For the retrospective arm of the study, consent was waived off by the Ethical committee.

Study Procedure

A total of 32 patients were recruited for the retrospective arm of the study and for the prospective arm 78 patients were recruited. For the prospective arm, data was collected from the patients who came to the Emergency Department with acute stroke in the window period (three hours) or in the extended window period (4.5 hours). NIHSS score (12) at presentation was documented for each patient. All the eligible patients received thrombolytic therapy with alteplase at a dose of 0.9 mg/kg (10% as a bolus and the rest as an infusion over 1 hour) (2),(6). Onset-to-door time, door-to-imaging time, door-to-needle time, and onset-to-needle time were assessed. CT/MRI report after 24 hours of thrombolysis was followed-up. Neurological outcome at 24 hours post-thrombolysis was assessed using NIHSS score. Functional outcome at 90 days was assessed using MRS score (Table/Fig 1) (13),(14).

The retrospective study collected the required data from the hospital records, and the patients were followed-up. NIHSS score decreasing by ≥4 points were defined as an improvement in neurologic status; increasing by ≥4 points as worsening of neurologic status (12). Those patients who had an MRS score of 0-2 at 90 days were classified as having “Favourable outcome” and those patients whose MRS score was between 3-6 were classified as having “Unfavourable outcome” (13),(14).

Statistical Analysis

Data were entered using Microsoft excel 2016 and STATA v.14 was used for statistical analysis. Continuous variables with skewed distribution were presented as median (range) while categorical variables were presented as count (percentages). Statistical comparisons were performed between subgroups using the χ2 test, Fischer’s-exact test, Wilcoxon signed-rank test, and Mann-Whitney U-test as indicated for dichotomous or continuous variables. For all statistical analyses, a p-value of <0.05 was taken as statistically significant.

Results

The study included 110 subjects who fulfilled the inclusion criteria. The median age of the study population was 65 years. The minimum age included in the study was 32 years and the maximum age was 89 years. There were 78 (70.90%) males and 32 (29.10%) females in the study group. The age and gender distribution is given in (Table/Fig 2).

Critical time intervals: NINDS has established critical in-hospital time goals for the assessment and management of patients with suspected stroke (5),(6). This includes onset-to-door time, door-to-imaging time, door-to-needle time, and onset-to-needle time. Onset-to-door time implies how fast the patient reaches the hospital from the time of onset of symptoms. Door-to-imaging time should preferably be within 25 minutes of arrival. Initiation of fibrinolytic therapy, if appropriate, within one hour of arrival to the hospital is the ideal door-to-needle time. Onset-to-needle time which is defined as the time from the onset of symptoms to the initiation of thrombolytic therapy should be within 4.5 hours (6). Various critical time intervals as observed in the study are shown in (Table/Fig 3).

NIHSS score at presentation: The median NIHSS score on presentation was 11, with a range from 5-27.

NIHSS score 24 hours post-thrombolysis: The median NIHSS score at 24 hours was 6, with a range from 0-32. Improvement in neurological function, as defined by an improvement in NIHSS score (NIHSS Score reduction by 4 or more) was found in 73 patients (66.4%). Worsening of neurological function, defined by an increase in NIHSS score by 4 or more was present in 12 patients (10.9%). No significant difference in NIHSS score (from -3 to +3 difference) was seen in 25 patients (22.7%) (Table/Fig 4).

Imaging results after 24 hours post-thrombolysis: Imaging (MRI Brain/CT Brain) done after 24 hours revealed that 35 patients (32%) had intracerebral haemorrhage/haemorrhagic transformation of infarct following thrombolysis. Symptomatic intracerebral haemorrhage as defined by haemorrhage associated with worsening of NIHSS over 4 points was seen in 10 patients (9%) in the study population (Table/Fig 5).

Modified Rankin scale score at 90 days: At 90 days follow-up, 76 patients (69.1%) became functionally independent with an MRS score of 0-2 (favourable outcome), 34 patients (30.9%) had an MRS score between 3-6 (unfavourable outcome). Seven patients (6.4%) died during the three-month period. This is shown in (Table/Fig 6).

Outcome analysis in terms of NIHSS score at 24 hours and functional outcome at 90 days: The median NIHSS scores at baseline and at 24 hours were 11 (range: 5-27) and 6 (range: 0-32), respectively. There was a significant difference between the NIHSS scores at baseline and at 24 hours in patients who had received intravenous thrombolysis therapy (p-value <0.001) (Table/Fig 7).

Among the 73 patients who had improvement in NIHSS score after 24 hours, 59 patients (80.8%) had MRS score less than or equal to 2 (favourable outcome) and 14 patients (19.2%) had MRS Score more than 2 (Unfavourable outcome). All the 12 patients who had worsening in NIHSS score after 24 hours, were found to have MRS score more than 2 at 90 days. Among the 25 patients who didn’t have much difference in their NIHSS score after 24 hours, 17 patients (68%) had favourable outcomes and 8 patients (19.2%) had unfavourable outcomes. A significant association was observed in this study between NIHSS score after 24 hours -post-thrombolysis and 90 days functional outcome (p-value <0.001) (Table/Fig 8).

Association between critical time intervals and NIHSS score 24 hours post-thrombolysis: Of the various critical time intervals, a statistically significant association was observed only with Onset-to-door time and 24 hours post-thrombolysis NIHSS score (p-value 0.031) (Table/Fig 9). It was observed that those who presented within three hours of symptom onset had a significant improvement in NIHSS score at 24 hours compared to those who presented after 3 hours but within 4.5 hours.

Association between critical time intervals and 90 days functional outcome as per Modified Rankin scale score: The Onset-to-door time, door-to-imaging time, door-to-needle time, and onset-to-needle time were compared between the groups with favourable and unfavourable outcomes. None of the parameters differed signi?cantly between the groups (Table/Fig 10).

Discussion

Thrombolytic therapy is the standard of care in acute ischaemic stroke. However, this therapy must be given in the first 4.5 hours after the onset of symptoms to be effective. A series of clinical tasks, including initial assessment, imaging, neurology consultation, image interpretation, excluding contraindications, procurement of medications, informed consent, etc must be done before administration of thrombolytic therapy. Accomplishing these clinical tasks within the limited window period is challenging. Compliance to the critical in hospital time goals set by NINDS may help in overcoming the constraints (5). These critical time intervals are door-to-imaging time (<25 minutes), door-to-needle time (<60 minutes) and onset-to-needle time (<4.5 hours). In this study, adherence to the time sensitive goals and its relationship with immediate and 90 days neurological outcome were analysed.

In this study, only 39 (35.5%) patients received thrombolytic therapy within one hour of hospital arrival. In the remaining 71 patients (64.5%), the recommended door-to-needle time was not achieved. Other studies conducted in India showed that door-to-needle time varied widely from 27-140 minutes (15),(16). This reflects the constraints in providing thrombolytic therapy in a developing country like India. Analysis of the door-to-imaging time in this study showed that this was more than 25 minutes in the majority of the patients (58.2%). This might be a major limiting step that has led to the prolongation of the door-to-needle time as well as the onset-to-needle time. Further studies are needed to look into other factors that may cause delay in thrombolytic therapy. A significant improvement in NIHSS score after 24 hours of thrombolysis was seen in 66.4% of patients. This was slightly more when compared with other studies done in India where an improvement in NIHSS score was observed for 32-64% of the study subjects (16),(11).

On analysing the functional outcome and neurological recovery, it was observed that 69.1% of patients who received thrombolysis became functionally independent at 90 days. Previous studies in India reported a similar efficacy for thrombolytic therapy (48-78%) (11),(16),(17). Functional independence with an MRS of 0-2 at three months was reported in 84% of patients in the study done by Tsivgoulis G et al., in Greece (18). In the study by Chao AC et al., in Taiwan, MRS of 0-2 at 90 days was observed in 53.4 % of the study group (19). Even though in this study, critical time intervals could not be achieved as per the desired targets, the overall outcome is comparable to other studies.

A significant association between onset-to-door time and 24 hours NIHSS score improvement was observed in this study. The patients who reached the hospital in the window period (within 3 hours) had a better improvement in NIHSS score at 24 hours after receiving thrombolytic therapy compared to those who reached the hospital in the extended window period (between 3-4.5 hours). There was no significant change in the functional outcome at 90 days in these two groups. This difference in finding may be attributed to the lower number of patients in the extended window period group compared to the window period (4.5% and 95.5%, respectively).

Similarly, it has been observed that a significant association exists between 24-hour post-thrombolysis NIHSS score and 90 days functional outcome. Those who have demonstrated significant improvement in NIHSS score after 24 hours of receiving thrombolysis are more likely to achieve favourable functional outcomes at 90 days. All the 12 patients who had worsening of their NIHSS score after 24 hours were eventually found to have unfavourable neurological outcomes at 90 days. This finding was in congruence with the results of the previous studies by Rangaraju S et al., and Heitsch L et al., where 24-hour NIHSS score was found to be a strong predictor of 90-day functional outcome in stroke patients (20),(21). The NIHSS score at 24 hours can prove to be a valuable tool to prognosticate the patients with ischaemic stroke who have received thrombolytic therapy.

Further studies are needed to validate the role of post-thrombolytic NIHSS score as a tool to predict outcome of thrombolytic therapy. The real-life constraints in achieving time bound goals for successful implementation of thrombolytic therapy has to be identified and addressed in a resource limited country like India.

Limitation(s)

The main limitation of the study was that it was a single-centre observational study. The study had included retrospective analysis and relied upon the documented timings and scores which might not be fully accurate.

Conclusion

The favourable functional outcome at 90 days was established following the intravenous thrombolytic therapy for acute ischaemic stroke. In a majority of patients, the recommended door-to-imaging time and door-to-needle time were not met reflecting the barriers in implementing timely thrombolytic therapy. The NIHSS score at 24 hours post-thrombolysis when compared to the baseline was determined as a good predictor of the neurological outcome at 90 days. Also, subjects who presented within three hours of symptom onset had a significant improvement in NIHSS score at 24 hours compared to those who presented after three hours.

References

1.
Feigin VL, Stark BA, Johnson CO, Roth GA, Bisignano C, Abady GG, et al. Global, regional, and national burden of stroke and its risk factors, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-20. [crossref] [PubMed]
2.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-87. [crossref] [PubMed]
3.
Bluhmki E, Chamorro Á, Dávalos A, Machnig T, Sauce C, Wahlgren N, et al. Stroke treatment with alteplase given 3· 0-4· 5 h after onset of acute ischemic stroke (ECASS III): Additional outcomes and subgroup analysis of a randomized controlled trial. Lancet Neurol. 2009;8(12):1095-02. [crossref] [PubMed]
4.
Lees KR, Bluhmki E, Von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375(9727):1695-03. [crossref] [PubMed]
5.
Marler JR, Jones PW, Emr M. Setting new directions for stroke care: Proceedings of a national symposium on rapid identification and treatment of acute stroke. The Institute; 1997. [crossref]
6.
Jauch EC, Cucchiara B, Adeoye O, Meurer W, Brice J, Yu-Feng Chang, et al. Part 11: Adult stroke: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 suppl 3):S818-28. [crossref]
7.
Zuckerman SL, Magarik JA, Espaillat KB, Kumar NG, Bhatia R, Dewan MC, et al. Implementation of an institution-wide acute stroke algorithm: Improving stroke quality metrics. Surg Neurol Int. 2016;7(Suppl 41):S1041-48. [crossref] [PubMed]
8.
Tai YJ, Weir L, Hand P, Davis S, Yan B. Does a ‘code stroke’ rapid access protocol decrease door-to-needle time for thrombolysis? Intern Med J. 2012;42(12):1316-24. [crossref] [PubMed]
9.
González RG, Copen WA, Schaefer PW, Lev MH, Pomerantz SR, Rapalino O, et al. The Massachusetts General Hospital acute stroke imaging algorithm: An experience and evidence-based approach. J Neurointerv Surg. 2013;5(suppl 1):i7-12. [crossref] [PubMed]
10.
Abraham SV, Krishnan SV, Thaha F, Balakrishnan JM, Thomas T, Palatty BU. Factors delaying management of acute stroke: An Indian scenario. Intern J Crit Illn Inj Sci. 2017;7(4):224-30. [crossref] [PubMed]
11.
Owais M, Panwar A, Valupadas C, Veeramalla M. Acute ischemic stroke thrombolysis with tenecteplase: An institutional experience from South India. Ann Afr Med. 2018;17(2):90-93. [crossref] [PubMed]
12.
Brott T, Adams Jr HP, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: A clinical examination scale. Stroke. 1989;20(7):864-70. [crossref] [PubMed]
13.
Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. stroke. 1988;19(5):604-07. [crossref] [PubMed]
14.
Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: Implications for stroke clinical trials: A literature review and synthesis. Stroke. 2007;38(3):1091-96. [crossref] [PubMed]
15.
Padma MV, Singh MB, Bhatia R, Srivastava A, Tripathi M, Shukla G, et al. Hyperacute thrombolysis with IV rtPA of acute ischemic stroke: Efficacy and safety profile of 54 patients at a tertiary referral center in a developing country. Neurol India. 2007;55(1):46-49. [crossref] [PubMed]
16.
Salam KA, Ummer K, Pradeep Kumar VG, Noone ML, Laila A, Ragini J. Intravenous thrombolysis for acute ischemic stroke: The Malabar experience 2003 to 2008. J Clin Neurosci. 2009;16(10):1276-78. [crossref] [PubMed]
17.
Ghafoor F, Khan F, Shehna A. Real-world effectiveness of intravenous stroke thrombolysis is more than the expectation of practicing neurologists. J Neurosci Rural Pract. 2018;9(3):331-35. [crossref] [PubMed]
18.
Tsivgoulis G, Sharma VK, Mikulik R, Krogias C, Haršány M, Shahripour RB, et al. Intravenous thrombolysis for acute ischemic stroke occurring during hospitalization for transient ischemic attack. Int J Stroke. 2014;9(4):413-18. [crossref] [PubMed]
19.
Chao AC, Hsu HY, Chung CP, Liu CH, Chen CH, Mu-Huo Teng M, et al. Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group. Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study. Stroke. 2010;41(5):885-90. [crossref] [PubMed]
20.
Rangaraju S, Frankel M, Jovin TG. Prognostic value of the 24-hour neurological examination in anterior circulation ischemic stroke: A post hoc analysis of two randomized controlled stroke trials. Interv Neurol. 2016;4(3-4):120-29. [crossref] [PubMed]
21.
Heitsch L, Ibanez L, Carrera C, Binkley MM, Strbian D, Tatlisumak T, et al. Early neurological change after ischemic stroke is associated with 90-day outcome. Stroke. 2021;52(1):132-41. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/58866.17037

Date of Submission: Jul 04, 2022
Date of Peer Review: Aug 02, 2022
Date of Acceptance: Oct 16, 2022
Date of Publishing: Nov 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 06, 2022
• Manual Googling: Oct 12, 2022
• iThenticate Software: Oct 14, 2022 (17%)

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