Neurological Disorders And Stroke Research Articles

Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment.

Post-thrombotic intracerebral hemorrhage (ICH) is experienced by 6-8% of stroke patients and is associated with multiple factors, including acquired coagulopathy induced by the thrombolytic drug. The objective of this study was to assess the outcome of the intravenous (IV) administration of fibrinogen concentrate in a series of acute stroke patients who developed iatrogenic fibrinogen critical depletion after IV thrombolysis. Of the 39 ischemic stroke patients treated with IV thrombolysis with a severe hypofibrinogenemia requiring infusion with IV fibrinogen concentrate, 30 patients were treated with 2 g of IV recombinant tissue plasminogen activator (rt-PA), followed by further doses until the fibrinogen level reached 200 mg/dL in hemorrhagic patients or 100 mg/dL in non-hemorrhagic patients, and 9 were treated with IV rt-PA followed by endovascular thrombectomy. Preand post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) scores were statistically different for the Cochran-Mantel-Haenszel test overall (p = 0.0002), at 24-hour evaluation (p = 0.0455) and at 7-day assessment (p = 0.0006). Within the first 7 days post-thrombolysis, the brain computed tomography (CT) scans showed that 20/39 (51.28%) patients had ICH. Of the whole sample, 25.6% of the ICH patients had symptomatic intracerebral hemorrhage (SICH), according to National Institute of Neurological Disorders and Stroke (NINDS) classification. After rt-PA treatment, the median pre-thrombolysis fibrinogenemia of 332 mg/dL significantly dropped to 133 mg/dL (p < 0.0001). After the fibrinogen concentrate infusion, the median level of fibrinogenemia rose to 160 mg/dL, which was significantly higher than the median postthrombolysis levels (p < 0.0001). Recanalization was observed in 25/28 patients (89.29%): complete in 18 and partial in 7 patients. After fibrinogen IV infusion, no thrombotic complications were seen in 37 out of 39 patients (94.77%); 2/39 (0.05%) patients experienced a pulmonary embolism, 1 of them a segmental one. This study showed the clinical safety of administering IV fibrinogen concentrate in order to increase plasma fibrinogen levels in a series of acute stroke patients with iatrogenic fibrinogen depletion after IV thrombolysis.

Effectiveness of a Psychological Intervention Delivered by General Nurses for Alcohol Use Disorders in People Living with HIV in Zimbabwe: A Cluster Randomised Controlled Trial

Background: Limited data exist on the effectiveness of interventions for alcohol use disorders (AUD) in people living with HIV which can be delivered in general health care settings in low- and middle- income countries (LMIC). Methods: Sixteen public health facilities (clusters) were selected nationally through stratified randomisation and then randomised 1: 1 to Motivational Interviewing blended with brief Cognitive Behavioural Therapy (MI-CBT) or to Enhanced Usual Care (EUC). Inclusion criteria for individuals were adults aged 18 years-plus living with HIV who met criteria for AUD defined by Alcohol Use Disorders Identification Test (AUDIT) score of 6 for women and 7 for men. Nurses working in these health facilities were trained to deliver the treatments. Participants in the MI-CBT clusters received 10 sessions. Participants in EUC clusters received 3 sessions of psychoeducation based on the WHO Mental Health Gap Intervention Guide. The primary outcome was change in the AUDIT score at 6 months post-randomization. Secondary outcomes were viral load and functioning, measured by the WHODAS 2.0. A random-effects analysis-of-covariance model was used accounting for the cluster design. Findings: 234 participants were enrolled across 16 clinics, with a mean age of 43.3 years (9.1). 78.6% of the participants were male. 175 (74.8%) were followed up at 6 months. At 6 months follow-up AUDIT score fell by 6.15 (95% CI -6.3; -6.0) points in the MI-CBT arm and by 3.09 (95% CI -3.2; -2.9) points in the EUC arm. The drop in the AUDIT score was significantly greater in the MI-CBT arm compared to EUC: mean difference -2.26 (95% CI -4.53 to -0.01) (p=0.05). The viral load fell and general function improved in both arms with no statistically significant difference between arms. Interpretations: Nurses in government primary care and hospital facilities in low-income countries can be trained to deliver low-cost interventions that can reduce AUDs among PLWH. For people living with HIV, studies with long-term follow-up are needed to show whether longer interventions using Motivational Interviewing-CBT techniques are cost-effective compared to short interventions based on psychoeducation and feedback about alcohol use. Trial Registration: Pan African Clinical Trial Registry, PACTR201509001211149. Funding Statement: Research reported in this publication was supported by the Fogarty International Center (Office of The Director, National Institutes Of Health (OD), National Institute of Nursing Research (NINR), National Institute of Mental Health (NIMH), National Institute of Dental & Craniofacial Research (NIDCR), National Institute of Neurological Disorders and Stroke (NINDS), National Heart, Lung, and Blood Institute (NHLBI), Fogarty International Center (FIC)) of the National Institutes of Health, award D43 TW010137, the DELTAS Africa Initiative [DEL-15-01]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [DEL-15-01] and the UK government, Grant Number D43TW010313-02S3 from the National Institutes of Health, Fogarty International Center and the National Research Founding through Funding to Professor Soraya Seedat SARChi Research Chairs. The study also received support from King’s College London Partnership Fund for viral load testing. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Fogarty International Center or the National Institutes of Health, the DELTAS Africa Initiative, King’s College London and the National Research Foundation SARChi Research Chairs. As an FIC scholar, MM also received research training from the Clinical and Translational Science Institute (award UL1TR001412). Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: Stellenbosch Health Research Ethics Committee (HREC) (SI/10/14/222) and the Medical Research Council of Zimbabwe (MRCZ) (A/1936) provided ethics approval.

Guillain-Barré syndrome in Denmark: a population-based study on epidemiology, diagnosis and clinical severity.

To describe the epidemiology and clinical heterogeneity of Guillain-Barré syndrome (GBS) in Denmark and to compare a population-based cohort to prospectively included patients in the International GBS Outcome Study (IGOS). The incidence rate (IR) of GBS in Denmark from September 2012 to December 2015, applying the National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria, was estimated and the level of diagnostic certainty was described with the Brighton criteria. All cases registered with a diagnosis of GBS or other inflammatory neuropathies in the Danish National Hospital Registry were reviewed for diagnostic criteria and for information on treatment and clinical course. A total of 299 GBS cases were confirmed, corresponding to a crude IR of 1.59 (95% CI 1.42-1.78) per 100,000 per year. The Brighton criteria level 1-3 of diagnostic certainty was met in 279 (93%) of the patients. Thirty-five percent of the patients were mildly affected (GBS disability score < 3) and a correlation between high age and high disability score at nadir was found (Spearman's rank correlation coefficient 0.42, p < 0.0001). The group of 89 (30%) patients who were enrolled in IGOS had higher GBS disability score at nadir, were admitted 5days earlier, reached nadir 4days faster, and a larger proportion received treatment with IVIg (all p < 0.05). The epidemiology and full clinical spectrum of GBS are described in a population-based study. This includes a larger proportion of milder cases that are underrepresented in prospective cohorts such as IGOS.

A common data language for biomechanical devices used in TBI clinical research: The National Institute of Neurological Disorders and Stroke (NINDS) and Department of Defense (DoD) CDE recommendations

ObjectiveThe NINDS Common Data Element (CDE) project provides data standards for clinical research in neuroscience. NINDS/NIH and DoD collaborated to develop CDE recommendations for Biomechanical Devices in TBI. CDEs increase efficiency of clinical research studies by reducing study start-up time and cost, increasing data quality, facilitating data sharing and aggregation, and helping educate new clinical investigators.BackgroundIn January 2017, a working group (WG) of subject matter experts from academia, industry and the military convened to develop CDE recommendations for blast, blunt head impact and inertial-loading exposures measured by biomechanical devices. These CDEs are available as a subset of the TBI recommendations under the Disease/Injury Related Events Domain and Biomechanical Devices Sub-Domain on the NINDS CDE website.Design/methodsThe WG divided into 3 subgroups: Head Accelerometry, Impact Video and Blast Exposure to review commonly collected data and analysis methods. The Head Accelerometry subgroup focused on data captured by kinematic sensors in sports/activities. The Impact Video subgroup addressed the use of video information to confirm device measurements. The Blast Exposure subgroup compared data from research sources using blast overpressure sensors. Subgroup recommendations were reviewed internally across the WG before being posted for public review.ResultsThe WG's end products are summaries, CDE metadata and template case report forms. Assigned classifications guide researchers in selecting CDEs: Supplemental-Highly Recommended (essential for specified conditions, study types or designs), Supplemental (commonly collected, but not required), and Exploratory (reasonable to use, but require further validation). Version 1.0 recommendations were made available for use through the NINDS CDE website in late February 2018.ConclusionThese new CDE recommendations will facilitate robust metadata analysis and data-sharing. NINDS encourages use of CDEs for all clinical research in neuroscience. NINDS CDEs are a dynamic resource, which is updated periodically based on the current state of science.

Streamlining clinical research: The National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) and Department of Defense (DoD) sport-related concussion common data element (CDE) recommendations

ObjectiveThe purpose of the NINDS CDE project is to educate new clinical investigators, increase efficiency and effectiveness of clinical research studies and treatment, increase data quality, facilitate data sharing, significantly reduce study start-up time, and more effectively aggregate information into significant metadata results. In 2016, as part of the NINDS CDE project to develop data standards for all clinical neuroscience research, NINDS, NIH and the DoD initiated the development of Sport-Related Concussion (SRC) CDEs.BackgroundTBI CDE recommendations were published on the NINDS CDE website in 2010, but lacked a thorough inclusion of SRC. In August 2016, a new SRC-specific working group (WG) began developing and identifying CDEs, template case report forms (CRFs), and guidelines to assist investigators conducting SRC-specific clinical research studies.Design/methodsThe CDE WG, which consisted of 34 worldwide SRC research experts, met regularly via teleconference over several months. The WG was divided into 3 subgroups to examine SRC during defined periods relative to time of injury: Acute (72 hours post-concussion), Sub-Acute (3 days-3 months post-concussion) and Persistent/Chronic (3 months and greater post-concussion).ResultsVersion 1.0 of the SRC CDEs were available on the NINDS CDE website in June 2017. These include Core and Supplemental, Highly Recommended CDEs or instruments for cognitive measures and symptom checklists, as well as, other outcomes and endpoints, and sample CRFs for domains typically included in clinical research studies (e.g., vestibular, oculomotor, balance, anxiety, depression).ConclusionThe NINDS CDEs are reviewed and updated regularly as research advancements or changes to specific recommendations are deemed appropriate. Because the CDEs are an evolving resource, continued feedback is important for improved use and utility. The use of SRC CDE recommendations is highly encouraged for SRC related researchers as they serve as a valuable starting point and facilitate streamlining and sharing data.

Comprehensive genotyping of the C9orf72 hexanucleotide repeat region in 2095 ALS samples from the NINDS collection using a two-mode, long-read PCR assay

Objective: Expansion of the G4C2 repeat tract in the C9orf72 gene is linked to frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we provide comprehensive genotyping of the C9orf72 repeat region for the National Institute of Neurological Disorders and Stroke (NINDS) ALS collection (n = 2095), using a novel bimodal PCR assay capable of amplifying nearly 100% GC-rich sequences. Methods: A single-tube 3-primer PCR assay mode, resolved using capillary electrophoresis, was used for sizing up to 145 repeats with single-repeat accuracy, for detecting expansions irrespective of their overall size, and for flagging confounding 3′ sequence variations (SVs). A modified two-primer PCR mode, resolved via agarose gel electrophoresis, provided further size information for hyper-expanded samples (>145 repeats) up to ∼5.8 kb amplicons (∼950 G4C2 repeats). Results: Within the evaluated cohort, 177 (8.4%) samples were expanded, with 175 (99%) samples being hyper-expanded. 3′-SVs were identified in 64 (3.1%) samples, and were most common in expanded alleles. Genotypes of all 606 (29%) homozygous samples were confirmed using an orthogonal PCR assay. Conclusion: This study and PCR method may improve and standardize molecular characterization of the C9orf72 locus, and have the potential to inform phenotype–genotype correlations and therapeutic development in ALS/FTD.

Statements of Mentorship.

The Landis Award for Outstanding Mentorship was created in 2018 by the National Institute of Neurological Disorders and Stroke (NINDS) to recognize that “mentorship and training are critical to the development of exceptional future scientists” and to honor the legacy of former NINDS Director Story Landis, PhD, in mentoring generations of neuroscientists. I was honored to be nominated by my mentees and then selected by the committee as part of the inaugural group that received the award. While profoundly touched by the recognition, I am the first to admit that in mentoring, my aspirations exceed my capacities or training (and anybody who has worked in my lab will be the second to admit that). My mentorship skills are a work in progress. Yet unlike scientific ideas, which are also “works in progress” that benefit from the critiques of our peers, mentoring approaches seldom benefit from the comments and wisdom of our colleagues and mentees. For example, I must have written, in the 10 years I have been faculty member, dozens of research statements and plans, progress reports, and grants that have all benefited from the collective wisdom of my colleagues and mentees. My science is better for it. Yet, when it comes to one of the most important activities I do, the training of mentees, it was in preparing for the Landis Award that I wrote my very first Statement of Mentorship. To be sure, one could argue that writing a Statement of Mentorship is not necessary or even important to being a good mentor. That the tasks necessary for being a good mentor are self-evident. Some might even argue that the best way to be a good mentor is to focus solely on the scientific ideas, not so much on the individual mentee. Yet I would argue that the …

NIH/NINDS and DoD CDE Recommendations: Biomechanical Devices in Head Impact and Blast Exposure Dynamics

To facilitate study start-up and data sharing in blunt head impact and blast exposure biomechanical device research, the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) and Department of Defense (DoD) collaborated to develop version 1.0 Common Data Element (CDE) recommendations. This was achieved through the development of standardized definitions and collection frameworks for data collected in research utilizing biomechanical devices.

Harmonizing Data Sharing: NIH/NINDS and DOD Sport-Related Concussion Common Data Elements (CDE) Recommendations

To increase the efficiency and effectiveness of clinical research studies and clinical treatment, the National Institute of Neurological Disorders and Stroke (NINDS)/National Institutes of Health (NIH) and Department of Defense (DOD) developed the Sport-Related Concussion (SRC) CDE recommendations to increase data quality, facilitate data sharing across studies, significantly reduce study start-up time, and help educate new clinical investigators.

Brief history of anti-seizure drug development.

SummaryThe mainstay of therapy for epilepsy is anti‐seizure drugs (ASDs, also referred to as anticonvulsants and anti‐epileptic medications). Through much of the past century, only a handful for ASDs were available for clinical use. However, with the creation of the U.S. National Institutes of Health/National Institute of Neurological Disorders and Stroke (NINDS)–sponsored Anticonvulsant Screening Program (ASP), coupled with the emergence of high‐throughput screening platforms and methodologies, and advances in our understanding of the fundamental neurobiology of epilepsy, ASD development has greatly accelerated over the past 25 years. More than 18 new ASDs have been approved for clinical use since the inception of the ASP. Despite this remarkable success and the emergence of drugs possessing more favorable pharmacokinetic profiles that act on novel molecular targets, there has been increasing recognition that the paradigms for drug discovery have not yielded significant improvements in therapeutic efficacy, and that disease modification (i.e., anti‐epileptogenesis), among other challenges, must be addressed. Thus, with the renewed framework and mission of improving the lives of people with epilepsy, the name of the ASP was changed to the Epilepsy Therapy Screening Program (ETSP). This review briefly summarizes the history of ASD development and outlines some of the challenges and opportunities for the next generation of drug therapies for the epilepsy field.

Knowledge and Attitudes of Saudi Emergency Physicians toward t-PA Use in Stroke.

Background and Objectives Tissue plasminogen activator (t-PA) within 4.5 hours from onset improves outcome in patients with ischemic stroke and has been recommended by several international guidelines. Since its approval in 1996, the debate among emergency physicians continues particularly around the result interpretation of the first positive randomized controlled trial, the National Institute of Neurological Disorders and Stroke (NINDS) clinical trial. This lack of consensus might negatively affect the delivery of effective stroke care. Here we aimed to assess the knowledge and attitude of Saudi emergency physicians toward t-PA use within 4.5 hours of onset in acute ischemic stroke. Methods A web-based, self-administered, locally designed questionnaire was sent to all emergency physicians practicing in the city of Riyadh from January to September 2017. Results Out of 450 emergency physicians, 122 from ten hospitals in Riyadh participated in the survey, with a 27% response rate. The majority of participants were men (78%), and their mean age was 40 ± 8 years. Half of the participants were board certified, and 36% were consultants. Half of the participants consider the evidence for t-PA use in stroke within 4.5 hours of stroke onset to be controversial, and 41% recommend against its use due to lack of proven efficacy (37%), the risk of hemorrhagic complications (35%), lack of stroke expertise (21%), and medicolegal liability (9%). Nearly half were willing to administer IV t-PA for ischemic stroke in collaboration with remote stroke neurology consultation if telestroke is implemented. Conclusion Our study detected inadequate knowledge and a negative attitude among Saudi emergency physicians toward t-PA use in acute stroke. This might negatively impact patient outcome. Therefore, we recommend developing urgent strategies to improve emergency physicians' knowledge, attitudes, and beliefs in the management of acute stroke.

National Institute of Neurological Disorders and Stroke and Department of Defense Sport-Related Concussion Common Data Elements Version 1.0 Recommendations.

Through a partnership with the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, and Department of Defense, the development of Sport-Related Concussion (SRC) Common Data Elements (CDEs) was initiated. The aim of this collaboration was to increase the efficiency and effectiveness of clinical research studies and clinical treatment outcomes, increase data quality, facilitate data sharing across studies, reduce study start-up time, more effectively aggregate information into metadata results, and educate new clinical investigators. The SRC CDE Working Group consisted of 32 worldwide experts in concussion from varied fields of related expertise divided into three Subgroups: Acute (<72 h post-concussion), Subacute (3 days-3 months post-concussion) and Persistent/Chronic (>3 months post-concussion). To develop CDEs, the Subgroups reviewed various domains, then selected from, refined, and added to existing CDEs, case report forms and field-tested data elements from national registries and funded research studies. Recommendations were posted to the NINDS CDE Website for Public Review from February 2017 to April 2017. Following an internal Working Group review of recommendations, along with consideration of comments received from the Public Review period, the first iteration (Version 1.0) of the NINDS SRC CDEs was completed in June 2017. The recommendations include Core and Supplemental-Highly Recommended CDEs for cognitive data elements and symptom checklists, as well as other outcomes and end-points (e.g., vestibular, oculomotor, balance, anxiety, depression), and sample case report forms (e.g., injury reporting, demographics, concussion history) for domains typically included in clinical research studies. The NINDS SRC CDEs and supporting documents are publicly available on the NINDS CDE website www.commondataelements.ninds.nih.gov . Widespread use of CDEs by researchers and clinicians will facilitate consistent SRC clinical research and trial design, data sharing, and metadata retrospective analysis.

Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets.

We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010-2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0-1); (4) 3-month functional independence (FI; mRS scores = 0-2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = -0.03 to -0.01), ECASS II (5.2% vs 4.4%, 95% CI = -0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = -0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = -0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = -0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = -0.03 to 0.06), or distribution in 3-month mRS scores (2 [1-4] vs 2 [0-4], 95% CI = -0.29 to 0.09) were documented between the 2 groups. Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89-97.

Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic Stroke: Results of Two Open-Label, Multicenter Trials.

Tenecteplase (TNK-tPA) is a promising third-generation plasminogen activator, because of its greater fibrin specificity and longer half-life than alteplase. There is a paucity of studies on intravenous thrombolysis using TNK-tPA in developing countries. The present study has been undertaken to compare the efficacy and safety of TNK-tPA with alteplase. Two studies were conducted. Study I was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2mg/kg) were compared. Study II was an open-label study in which TNK-tPA 0.2mg/kg bolus was compared with historical controls. The primary endpoint for studyI and studyII was an improvement of ≥ 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24h. Secondary endpoints for both studies were neurological improvement as assessed using the NIHSS score, modified Rankin Scale (mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability was defined as an mRS score of 0 or 1 and good functional recovery as a BI score of 50-90. Safety was assessed by the proportion of patients having symptomatic intracranial hemorrhage (sICH) within 36h and asymptomatic intracranial hemorrhage at 48h after treatment. In study I, 20 patients received 0.1mg/kg and 30 received 0.2mg/kg TNK-tPA. There was no significant difference in MNI at 24h between 0.1 and 0.2mg/kg TNK-tPA doses. The patients given 0.2mg/kg TNK-tPA had a significantly better 3-month outcome (minimal disability, p = 0.007). There was no sICH in studyI. In studyII, 62 patients(one lost to follow-up) received 0.2mg/kg TNK-tPA. MNI was noted in ten patients (16.4%), 3-month minimal disability was noted in 37 patients (60.7%), and good functional recovery was seen in 33 patients (54.1%). sICH occurred in one patient, and four patients died. Pooled data of patients in studyI and studyII receiving 0.2 mg/kg TNK-tPA were compared with data from the historical National Institute of Neurological Disorders and Stroke (NINDS) trial. For comparison, the primary endpoint of the NINDS trial (improvement on NIHSS of ≥ 4 points or a score of 0 at 24h) was taken. The primary endpoint though was not significantly different (58.2% vs. 47%, p = 0.08), but with TNK-tPA, greater neurological improvement, minimal disability (70.3 vs. 39%, p < 0.001) and good functional recovery (36.3 vs. 16%, p < 0.001) was noted at 3months. There was a lower incidence of sICH (1.1 vs. 6.4%, p = 0.05) and lower 3-month mortality (5.5 vs. 17%, p = 0.01) noted with TNK-tPA compared with alteplase. Intravenous TNK-tPA 0.2mg/kg administered within 3 hours of symptom onset seems to be well tolerated and effective optionin patients with acute ischemic stroke. Clinical Trials Registry-India, www.ctri.nic.in ; unique identifiers: CTRI/2009/091/000251 and CTRI/2015/02/005556.

Refining a Summer Biomedical Research Training Program for American Indian and Alaska Native (AIAN) Students

Literature shows that students who enter the science, technology, engineering, mathematics, and medical-related (STEMM) pipeline at earlier stages of their career are more likely to be successful. This is especially true for underrepresented and economically disadvantaged students. Despite the increasing number of students entering the pipeline, American Indian and Alaska Native (AIAN) students still have a higher attrition rate compared to other ethnic groups. Educators and government agencies have worked to improve the success rate for AIAN students across all levels and fields by developing various programs aimed at training and mentorship. In 2007, the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) in Bethesda, MD, increased their outreach efforts for recruiting AIAN students for the summer internship program. Our goal was to develop a culturally tailored research-training program that could recruit and retain AIAN students into STEMM degrees and careers. We adapted an existing program that provides training in biomedical science and mentorship at an NINDS research laboratory. From 2007 to 2016, of the 41 AIAN interns who participated, 35 (85%) remained in STEMM fields. Five interns obtained post baccalaureate positions at NIH and four entered graduate or medical school. These successful outcomes were brought about only after navigating myriad obstacles. We identified obstacles for AIAN student participation, and made adaptations to the summer internship. We made design decisions regarding recruitment, feasibility, lab placement and mentorship, supporting research and social networking, and sustaining AIAN culture. This design case highlights the obstacles and strategies for success that we developed.

Ninds/nih And Dod Sport-related Concussion Common Data Elements

PURPOSE: In 2016, the National Institute of Neurological Disorders and Stroke (NINDS)/National Institutes of Health (NIH) and the Department of Defense (DOD) began development of Sport-related Concussion (SRC) Common Data Elements (CDEs) to develop data standards for all funded clinical research in neuroscience with goal of increasing the effectiveness of clinical research studies and treatment by facilitating data sharing across studies. The purpose of this abstract is to report the findings from the SRC-CDEs. METHODS: The initial NINDS Traumatic Brain Injury (TBI) CDE recommendations created in 2010 included limited sport-related brain injury recommendations. In August 2016, a new SRC-specific CDE working group (WG) began developing and identifying CDEs, template case report forms (CRFs), data dictionaries and guidelines to assist investigators initiating and conducting SRC-specific clinical research studies. Comprised of 34 experts from around the world, the WG met regularly to review current collection of SRC data. The WG was divided into three subgroups to examine SRC over time: (1) Acute Subgroup (time of injury until 72 hours); (2) Subacute Subgroup (after 72 hours to 3 months); and, (3) Persistent/Chronic Subgroup (3 months and greater post-concussion). RESULTS: The SRC CDEs were released to the NINDS CDE website in June 2017. The recommendations include Core and Supplemental - Highly Recommended CDEs for cognitive measures and symptom checklists, as well as other outcomes and endpoints (e.g., vestibular, oculomotor, balance, anxiety, depression) and sample case report forms (e.g., injury reporting, demographics, history of concussion, concussion history) across acute, sub-acute and persistent/chronic. CONCLUSION: NINDS encourages the use of SRC CDEs by the clinical research community to standardize data collection and reporting. The NINDS CDEs are a continually evolving resource, and these newly developed SRC CDEs serve as valuable starting points for investigators to streamline research that informs treatments for SRC. This material is based upon work supported by the U.S Army Medical Research and Materiel Command’s Combat Casualty Care Research Program and funded by NIH contracts HHSN271201700064C and HHSN271201200034C.

Improving animal research reporting standards

For more than 30 years, individuals and organizations have expressed concerns about the quality of reporting the results from and details of research experiments that use animals. These concerns and efforts to establish better standards along with guidelines for researchers (see Sidebar A) have gained more attention and importance lately given the ongoing discussion about a “reproducibility crisis” in biomedical research along with similar efforts to further improve the welfare of laboratory animals. However, implementation of reporting standards by journals and adherence to these by authors is still patchy. Given this variation in awareness and implementation of current reporting standards, the International Council for Laboratory Animal Science (ICLAS) decided to seek to harmonize animal research reporting guidelines so as to encourage improvements in the quality of science where laboratory animals are involved. ICLAS, which was formed under the auspices of UNESCO in 1956 as an international scientific organization to advance human and animal health by promoting the ethical care and use of laboratory animals in research worldwide, believes that improving research reporting will aid the dissemination of responsible research practices worldwide and reduce the impact of cultural factors influencing the ethical use of animals. Here, we present simplified and general reporting principles that would make it easier for both journals and authors to report details of animal experiments. Adoption and implementation of these general principles could improve reproducibility of research results and animal welfare globally. ### Sidebar A: Further reading Papers outlining concerns regarding the reporting of animal experiments Smith JA, Birke L, Sadler D (1997) Reporting animal use in scientific papers. Lab Animal 31: 312–317 Alfaro V (2005) Specification of laboratory animal use in scientific articles: current low detail in the journals’ instructions for authors and some proposals. Methods Find Exp Clin …

Common Data Elements (CDEs) for Biomechanical Devices used in Blunt Head Impact and Blast Exposure Dynamics: The National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) and Department of Defense (DOD) Version 1.0 Recommendations (P2.012)

Common Data Elements (CDEs) for Biomechanical Devices used in Blunt Head Impact and Blast Exposure Dynamics: The National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) and Department of Defense (DOD) Version 1.0 Recommendations (P2.012)

Streamlining Clinical Research in Sports-Related Concussion: The National Institute of Neurological Disorders and Stroke (NINDS)/National Institutes of Health (NIH), and Department of Defense (DOD) Sport-Related Concussion Common Data Elements (CDEs) (P2.014)

Streamlining Clinical Research in Sports-Related Concussion: The National Institute of Neurological Disorders and Stroke (NINDS)/National Institutes of Health (NIH), and Department of Defense (DOD) Sport-Related Concussion Common Data Elements (CDEs) (P2.014)

A Common Language for Clinical Research Studies: The National Institute of Neurological Disorders and Stroke (NINDS) and Centers for Disease Control and Prevention (CDC) Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDEs) (P2.016)

A Common Language for Clinical Research Studies: The National Institute of Neurological Disorders and Stroke (NINDS) and Centers for Disease Control and Prevention (CDC) Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDEs) (P2.016)