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=The Calgary Stroke Program=

Overview
The Calgary Stroke Program is a multidisciplinary team of stroke experts who work in collaboration with Alberta Health Services and the University of Calgary to deliver comprehensive and coordinated stroke care across the stroke care continuum. Centrally located at the Foothills Medical Centre (FMC) in Calgary, Alberta, the program includes more than 20 stroke neurologists, physiatrists, and interventionists, 9 of whom are full academic faculty/ stroke clinician scientists. Some highlights from the program have been the 4 accreditations received from Accreditation Canada, and the numerous clinical trials including the ESCAPE trial, which have changed clinical practice worldwide.

Foundations (1991-2000)
Dr. Tom Feasby was hired as head of the Department of Clinical Neurosciences at the University of Calgary in September 1991. In 1992, Dr. Feasby created a selection committee, which determined that there was an overwhelming societal need for a stroke program. In response, in 1993, the Department created a Stroke Prevention Clinic (SPC) at the Foothills Medical Centre (FMC). The SPC was established with plans to form a team of neurologists and nurses who would see stroke patients and TIA patients, supplying antiplatelet therapy and carotid endarterectomy (the current treatments at the time). The initial SPC team consisted of three neurologists, Dr. Tom Feasby, Dr. Gary Klein, and Dr. Keith Hoyte, and two nurses, Teri Green, and Nancy Newcommon.

In order to provide more possible treatments, and establish a presence in the stroke community, the clinic participated in a clinical trial, the Randomized Trial of Tirilazad Mesylate in Patients with Acute Stroke (RANTTAS) an acute stroke study, with central study organization from the US, testing the use of what was known as a Lazeroid, a neuroprotectant drug to treat stroke.

The stroke program then looked to recruit a leader, who would organize and expand the team, and establish a research program. In September 1995, the team recruited Dr. Alastair Buchan, a clinician-scientist who had made influential discoveries about neuroprotection in his lab. Dr. Buchan led the newly created stroke program, and served as the chair in the professorship of stroke research, which was funded by the Heart and Stroke Foundation.

On December 14, 1995, a week after Dr. Buchan began at the FMC,  the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group published a paper titled “Tissue Plasminogen Activator for Acute Ischemic Stroke”, also known as the NINDS study 2. It demonstrated the effectiveness of alteplase (a recombinant form of human tissue plasminogen activator, or tPA) in treatment of stroke. In response to the new potential treatment, the team arranged to use a clot busting drug, alteplase, for their patients, and tested its use in the trial  “effectiveness of alteplase in treatment of acute ischemic stroke”, a 30-month trial which tracked 68 stroke patients between April 1996 and December 1998. In order to accommodate the time window that had been recommended by the NINDS trial, the stroke program created a “blocked bed” in unit 112. The blocked bed assured the team availability to admit a stroke patient eligible for alteplase, therefore ensuring fast treatment.

The stroke program also established collaboration with the Neurosurgery programs and Radiology Programs. Dr. William Hu was hired in July of 1996 as the first Neuroradiology interventionist in Calgary. Dr. Carla Wallace and Dr. Rob Sevick were working as sub-specialists in diagnostic neuroradiology as part of the Radiology department. Expanding the research and clinical team, in 1999, the stroke program hired new neurologists to share the stroke call with Nancy Newcommon and Dr. Buchan. The program hired Dr. Andrew Demchuk on staff, a neurologist who had completed a fellowship in Houston. Dr. Phil Barber joined as a fellow from Manchester in 1998, and Dr. Michael Hill joined as a fellow in July 1999, after completing his residency in Toronto. These new professionals brought brought unique and keen research interests that initiated further development of the program’s multifaceted approach to stroke care.

The Seaman Family MR Research Centre
In November of 1996, the fundraising Campaign Partners in Health provided funding for two new MRI machines for the FMC, a 3T MRI, and an intraoperative MRI. The magnets would provide the CSP with the equipment to provide detailed follow-up procedures for stroke treatment. In November of the same year,  Doc Seaman (a Calgarian philanthropist) and his family donated $2 million to the Calgary MR Research Centre, renaming it to the Seaman Family MR Research centre, and funding the programs the “high field MR cornerstone program”, and the “intraoperative MR program”. Located in close proximity to the Foothills Emergency Department, the Seaman Family Centre accommodates “world-leading rapid imaging of acute stroke”. Recent pursuits have included imaging of transient ischemic attack and minor stroke, along with imaging of small vessel disease. As part of the interoperative imaging program, Dr. Garnette Sutherland, a DCNS clinical professor and neurosurgeon part of the CSP, led the research team that developed the neuroArm, the first MR-compatible surgical robot. In 2011, Dr. Garnette Sutherland was honored the Order of Canada for his leadership and research in the development of the neuroArm.

Expanding the team (2000-2005)
In 2001, the team recruited neurologists Dr. Shelagh Coutts, Dr. James Kennedy, and Dr. Jessica Simon as clinical stroke fellows, and officially developed their fellowship program. The fellows in the program, who are recruited for a 1 or 2 year clinical or clinical/research fellowship serve as the backbone of the program. With the growing fellowship program, the team was able to expand their research interests, and thus, influence and improve clinical care.

On November 16th, 2001, the stroke program received funding for an acute stroke unit with 8 beds. The unit allowed for the centralization of all acute stroke care treatment, and split hyperacute and acute stroke care. Stroke units have shown to reduce length of stay by 3 days on average, and reduce the risk of major after TIA by 50%. In 2003, the unit received $1.1 million in funding for renovations from the Foothills Home Lottery. The unit was renovated to a 14 bed unit.

In 2005, Dr. Buchan returned to Oxford ultimately to become the Head of the Medical Sciences Division at Oxford University, and Dr. Demchuk and Dr. Hill became co-leaders of the program.

Provincial Care and New Research (2005-2010)
Before his departure, Dr. Buchan and Don Mazankowski in Edmonton established funding for a provincial stroke strategy. In 2005, the Alberta government provided a total investment of $42.5 million which would fund the Alberta Provincial Stroke Strategy (APSS) over the next 6 years. In Oct 2005, the funding came to fruition and health professionals from all 9 health regions across the province met for the first meeting. Members from the Calgary Stroke Program who served on the committee included: Dr. Demchuk who stood on the Emergency Services and Acute Care Committee, Dr. Tim Watson, who was the Southern Alberta Stroke Physician Lead, and Michael Suddes, who was on the Quality Improvement Subcommittee, and was the Lead for Alberta Stroke Improvement.

Over the 6 year period, quality improvement initiatives and guidelines implemented by the APSS helped improve the speed and efficiency of stroke care across the province. The number of centres in the province capable of giving alteplase more than tripled from 5 to 18, the number of stroke prevention clinics tripled, the median ED arrival to treatment times decreased, more TIA patients were treated within 3.5 to 4.0 hours, and the number of stroke patients treated at a stroke unit increased, all of which resulted in a decreased percentage of post-stroke complications and shorter length of hospital stay (and it corollary – faster discharge home times . The Calgary zone excelled in these areas and was the only zone that was able to achieve a median door to treatment time less than 60 minutes.

Along with participating in establishing provincial care, the program also sponsored its first multi-center clinical trial as a lead coordinating centre: the FASTER trial, which was published in the Lancet in 2007. Although the group did not pursue a second FASTER trial, the data from FASTER launched the POINT and CHANCE trials, both of which confirmed the initial results from FASTER.

Quality Improvement and Diversifying Research Areas (2010-2020)
Moving into the 2010’s, the team pursued Accreditation, an intensive process which surveys stroke centres for all the recommendations outlined in the Stroke Best Practice Recommendations, which cover stroke treatment from hyperacute to rehabilitation ( https://accreditation.ca/stroke-distinction/ ). After an 8 month preparation process, and a week-long survey period, the Calgary Stroke Program was awarded the Award of Distinction from Accreditation Canada. The program was the first stroke centre to seek out and receive the award from Accreditation Canada.

Through the process to organize and prepare for Accreditation, the program installed several new initiatives and facilities, and vastly improved the organization of their rehabilitation facilities. The program installed a new screening tool for dysphagia, TOR-BSST, and a new assessment tool for oral care. In 2012, the team, along with the help of Christianne Krassman and Darren Knox, also established an Early Supported Discharge Program, a rehabilitation service which provides patients with home-based support through Allied Health members, allowing patients to be discharged from hospital early.

In the early 2010’s interest grew for testing the use of endovascular thrombectomy (EVT) in the treatment of ischemic stroke. EVT had been used ‘off-label’ for the past 20 years, and it was known to have a Lazarus effect showing individual patient success; however, many had repeatedly failed in proving its efficacy in a clinical trial. The “Randomized assessment of Rapid endovascular Treatment of Ischemic Stroke” (ESCAPE) trial, led by program members Drs. Goyal, Demchuk and Hill, was the first trial to prove that use of EVT in the treatment of acute ischemic stroke improved outcomes, and increased the number of people who were able to return to independent living from 30% to 55%. As explained in interview with Dr. Goyal and Dr. Hill, the trial incorporated rapid brain imaging, and a novel workflow process to allow for faster treatment of patients, a focus that hadn’t been evident in the previous EVT trials done in the past years.

Following the ESCAPE trial,  establishing infrastructure across the province to facilitate EVT treatment meant improving acute care overall. Along with the stroke team in Edmonton, the CSP received funding for the “The Quality Improvement and Clinical Research” (QuICR) initiative in 2014. The funding permitted a three-pronged approach of clinical research, clinical care improvement and education. Clinical trials such as ESCAPE and ESCAPE NA-1, led by Dr. Hill and Dr. Mayank Goyal,  and TEMPO-1 and TEMPO-2, led by Dr. Shelagh Coutts, were launched and the team focused efforts on facilitating the provincial provisioning of EVT treatment by improving door-to-needle (DTN) times across the province. Many ideas used in the Hurry up and Start Treatment Early (HASTE) initiative run at the Foothills Medical Centre, led by Dr. Eric Smith, were used in the QuICR DTN improvement initiatives. The Strategic Clinical Network for Cardiovascular was created in 2013, and led many of the initiatives to implement workflow procedures across the province, including the Stroke Action Plan.

In addition to workflow studies and quality improvement funded by QuICR, team members urged a constant push for faster DTN times through small initiatives such as contests for the fastest DTN time, awarding small brain-shaped pins to the winners. The entire stroke collaborative effort across the province, directed by Dr. Noreen Kamal, was a milestone provincial initiative that has left its mark as a model program for improving care in an entire health system.

Throughout the 2010’s, the team also focused on expanding imaging research. Dr. Bijoy Menon, hired in 2010, and Dr. Mohammed Almekhlafi, who joined in 2018, developed and tested use of multiphase CTA in the PROVE-IT study, and in parallel, detailed analysis of the in vivo effect of thrombolytic drugs were tested in the INTERSECT clinical trial led by Dr. Demchuk. Multiphase CTA offered a pragmatic way of visualizing the pial collateral circulation on a mCTA scan.

Near the end of the 2010’s, the group  expanded their stroke rehabilitation research. After Dr. Sean Dukelow was hired in 2008, he established the Dukelow Lab, which focuses on researching stroke-specific rehabilitation treatments. Their current studies are the RESTART study, and the rTMS study. RESTART combines use of the KINARM, co-developed by Dr. Dukelow in the mid 2000s, with neuroimaging to get a detailed analysis of a patient's rehabilitation process. The combined use of robotics and neuroimaging helps to give patients a more personalized treatment. The rTMS study is currently on hold, but it looks at using magnetic pulses to stimulate and alter brain activity to help patients with aphasia to speak well again.

ASPECTS

 * Initially developed in 1996 as a way to monitor patients, the “Alberta Stroke Program Early CT Score”, or ASPECTS score, developed primarily by Dr. Buchan became a tool to assess CT-based stroke severity, and determine appropriate treatment, or eligibility for alteplase treatment.

CASES

 * From February 1999-2001 patients were recruited nationally for the Canadian Alteplase for Stroke Effectiveness Study (CASES), which examined the real-world effectiveness of thrombolysis for acute ischemic stroke . The study led to the final licensure of alteplase for stroke in Canada.

FASTER

 * The “Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence” (FASTER) pilot study, published in the Lancet, Neurology . showed that giving patients a combination of clopidogrel (antiplatelet drug) and aspirin within 24 hours if a transient ischemic attack prevented early recurrent stroke. It was the “first ever randomized trial of acute prevention in minor stroke and TIA patients”, and the first trial that the program sponsored as the lead coordinating centre.

CATCH

 * The “CT/CT Angiography and MRI Findings Predict Recurrent Stroke After Transient Ischemic Attack and Minor Stroke” (CATCH) study, published in 2012, found that in patients with TIA, narrowing in blood vessels was a strong predictor that the patient was at risk of a second attack . Results from the study showed that TIA patients could be safely managed as outpatients in a specialized TIA clinic if they had no arterial abnormality demonstrated on CTA. On July 22nd, 2013, the team opened a TIA clinic, the TIARA clinic, at the Foothills Medical Centre.

ENACT

 * In October 2012, the “Safety and efficacy of NA-a in patients with iatrogenic stroke after endovascular aneurysm repair” (ENACT) trial led by Dr. Hill was published in the Lancet.  It was a phase II study of nerinetide (NA-1) and showed that iatrogenic stroke associated with aneurysm coiling could be reduced by treatment with NA-1.

INTERSeCT

 * The “Association of Clinical, Imaging, and Thrombus Characteristics with Recanalization of Visible Intracranial Occlusion in Patients with Acute Ischemic stroke” (INTERSeCT) led primarily by Dr. Demchuk was published in 2018 in JAMA, providing detailed quantitative understanding of the rates of reperfusion after intravenous alteplase treatment depending upon where the occluding thrombus was located.

PROVE-IT

 * The study “Measuring Collaterals with Multi-phase CT Angiography in Patients with Ischemic Stroke” (PRoVE-IT) was completed in 2015 . Led by Dr. Bijoy Menon, the study examined the use of multiphase CTA comparatively against CTP and provided pragmatic imaging assessment of the pial collaterals.

TEMPO-1

 * The “Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke with Proven Occlusion” (TEMPO-1) trial, led by Shelagh Coutts, was published in 2015. While previously, most patients with minor stroke had been treated conservatively and not thrombolysed with alteplase, this study provided evidence of the safety and utility of tenecteplase, thereby setting the stage for TEMPO-2.

ESCAPE

 * The breakthrough trial, “Randomized assessment of Rapid endovascular Treatment of Ischemic Stroke” (ESCAPE), was published in The New England Journal of Medicine in March 2015. Led by Drs. Goyal, Demchuk and Hill, the study was a global trial that demonstrated the efficacy of endovascular thrombectomy in the treatment of ischemic stroke .  The ESCAPE trial was the second major trial to report this result and ultimately was one of several large trials that have resulted in a massive change in the way acute ischemic stroke is managed around the world.

ESCAPE NA-1

 * The “Efficacy and safety of nerinetide for the treatment of acute ischemic stroke” (ESCAPE NA-1) was published in the Lancet in February 2020 . Led by Drs. Hill and  Goyal, the trial tested use of the neuroprotectant nerinetide combined with EVT for treatment of acute ischemic stroke.  The trial was neutral overall, but further studies of nerinetide are planned.  As Dr. Hill explained in an interview with the Department of Clinical Neurosciences (DCNS) regarding the results in the trial, “not only is it possible to restore blood flow, but it’s possible to manipulate the biochemical processes that occur when blood flow to the brain is stopped” , link to interview , link to interview

HASTE
“Hurry up and Start Treatment Early” (HASTE) was an ongoing quality improvement project, which aimed to find methods to improve door-to-needle (DTN) times for acute ischemic stroke. The final report, published in 2017, proposed four protocol changes, two of which were novel, that proved to greatly decrease DTN times: taking the patient to CT on the ambulance stretcher, registering patient as unknown in the emergency department, implementing a STAT stroke protocol so that all team members are notified before the patient arrives, and administering alteplase while the patient is in the CT scanner 22.

QuICR
The Quality Improvement and Clinical Research (QuICR) initiative was a $5 million, 5-year AIHS Collaborative research and Innovates Opportunities (CRIO) grant which supported research from 2014-2019 28. The initiative aimed to reduce the median DTN times to 30 minutes, and treat 80% of all patients within 60 minutes by funding research and quality improvement ( https://www.ucalgary.ca/quicr/ ). As of 2019, the Foothills Medical Centre reached an average DTN time of close to 30 minutes 18.

The Calgary Stroke Program collaborated with the University of Alberta and the Strategic Clinical Network (SCN) to help implement findings from QuICR across Alberta. After the findings from the ESCAPE trial were published, the SCN formed the Endovascular Reperfusion Alberta (ERA) project to increase access to EVT throughout the province by mapping out EMS pathways. One of the statistical analysis done in partnership with Dr. Noreen Kamal, tested the efficiency of “drip and ship” versus the “mothership” method, to calculate if it was better to 1) receive alteplase at the nearest stroke centre, and then receive EVT at the primary stroke centre, or 2) travel directly to the primary stroke centre and receive both 33.

Major Awards/Grants/Recognition

 * Accreditation- In 2010, the Calgary Stroke Program was the first stroke centre to receive the Award of Distinction from Accreditation Canada . Since then, the CSP has been accredited 3 times, in 2012, 2014, and 2018.
 * 2020- Science Breakthrough Award. American Brain Foundation. ESCAPE Trial. Awarded to Mayank Goyal, Andrew Demchuk, Michael Hill for leadership of the ESCAPE Trial.
 * 2017- CARNA Award: Partners in Health.  Awarded to the Calgary Stroke Program
 * 2016- AHS President’s Excellence Award for Outstanding Achievement in Research for the ESCAPE trial
 * 2015- ASTECH Award 2015 for Society Impact for the ESCAPE trial
 * 2012- CIHR CMAJ Top Achievements in Health Research 2012 for developments in Stroke Research

Fellowship Program
The CSP fellowship program has educated a total of 88 fellows since its inception in 1999, and has expanded internationally. Fellows participate in the clinical and/or research part of the program. Fellows participate in the weekly Thursday morning stroke rounds, present at the weekly Thursday lunch rounds, attend weekly journal clubs Tuesday afternoons, and participate in the fellow academic half day every Wednesday.

== Current Facilities ==

Hyper acute stroke care

 * Telehealth
 * Working with Emergency Medical Services (EMS)


 * In 2017, EMS personell were trained on Los Angeles Motor Scale (LAMS) to help identify potential endovascular therapy (EVT) patients


 * Referral, Access, Advice, Placement, Information and Destination (RAAPID) team working with the FMC emergency department
 * Patient Care Unit (PCU) 112. Neuro step down ICU with TPA bed

Acute stroke care

 * Acute stroke unit: PCU 100 at FMC. Opened November 16th, 2001. Currently has 17 beds. Interprofessional team with nurses, clerical, allied health, and medical team. Acute stroke and early rehabilitation.
 * General neurosciences unit: PCU 111 at FMC

Rehabilitation

 * PCU 58 at FMC, providing tertiary neuro-rehabilitation


 * Dr. Vernon Fanning Centre, providing tertiary neuro-rehabilitation
 * Community Accessible Rehabilitation (CAR), provided at Peter Lougheed Centre, Sheldon M. Chumir Health Centre, and South Calgary Health Centre
 * Early Supported Discharge (ESD)

Stroke Prevention and Ambulatory Care Services

 * Stroke prevention clinic at FMC and South Health Campus


 * TIA Rapid Assessment (TIARA) clinic at FMC
 * Stroke Rehabilitation clinic

Community Re-Integration

 * INSPIRES program
 * Alberta Healthy Living Chronic Disease Management Programs

Current Clinical Trials
The Calgary Stroke Program is currently participating in approximately 30 trials, some of which are initiated by team members, and others which are run by colleagues who have sought out the CSP as a participating site. Some of the current trials include the ACT trial, EVOLVE, TEMPO-2, and ESCAPE NEXT. 

Affiliations

 * Member of Hotchkiss Brain Institute since 2004
 * Flagship program of the Department of Clinical Neurosciences, University of Calgary
 * Foothills Medical Centre
 * Alberta Health Services
 * Affiliations with the Heart and Stroke Foundation of Canada
 * Affiliations with the Stroke Clinical Network

See as Well

 * Department of Clinical Neurosciences (DCNS)
 * Cumming School of Medicine
 * University of Calgary (U of C)
 * Hotchkiss Brain Institute (HBI)
 * Seaman Family MR Research Centre
 * Alberta Health Services (AHS)
 * Foothills Medical Centre (FMC)
 * Fluid Biotech
 * Circle Neurovascular