Predictors for Prehospital Delay in Stroke Treatment
Predictors for Prehospital Delay in Stroke Treatment
Stroke is the second-leading cause of death worldwide and a leading cause of long-term
 disability. Annually 12,000 people in Denmark suffers a stroke; half of them will have
 long-term disabilities that may affect the activities of daily living. In addition to
 substantial individual suffering, stroke is also associated with considerable costs to
 society. Acute reperfusion therapies started within 4.5 to 6 hours (in some up to 24 hours)
 from symptom onset for acute ischaemic stroke (AIS) have revolutionized the acute stroke
 treatment and considerably improved the overall prognosis and mortality. However, only 15-25%
 of Danish patients are eligible to acute treatment. Numerous attempts to reduce both
 prehospital and in-hospital delay in stroke have been made, but much time is still lost in
 the prehospital phase.

 Many stroke patients do not recognize their own symptoms as signs of a stroke or do not
 understand the importance of calling Emergecy Medical Services (EMS) immediately. Others
 cannot call for help unless they have a bystander, because of cognitive impairment or
 aphasia. Some patients have a wait-and-see attitude, contact their GP or out-of-hours GP,
 which also can increase the delay. Educational stroke campaigns can increase knowledge,
 improve help-seeking behaviour and increase the number of patients eligible for reperfusion
 therapies. The foundation TrygFonden is planning a national stroke campaign in 2019.

 Aims:

 1. To explore the knowledge of stroke in stroke patients and bystanders.

 2. To explore the process from onset of symptoms until admission to hospital and the
 reasons for prehospital delay.

 3. To explore the association between stroke knowledge, help-seeking behaviour and
 receiving revascularization therapy.

 4. To evaluate the immediate effect of the national campaign six months after initiation.

 Material and methods:

 Study 1:

 Structured interviews of stroke patients (and bystanders) admitted to the Department of
 Neurology at Aarhus University Hospital and Regional Hospital West Jutland (Holstebro). The
 investigators will use the patient's medical record (EPJ) and the Danish Stroke Register
 (DSR) and map the patient's route from onset of symptoms to admission to stroke centre,
 including contact to general practitioner (GP), out-of-hours GP or Emergency Medical Services
 (EMS). For patients who have been in contact with their GP, the GP will receive an electronic
 questionnaire to explore the time- and event pathway from first contact until admitting the
 patient to hospital. The investigators will interview 500 patients and approximately 300
 bystanders over a period of 3 months.

 Study 2:

 The investigators will evaluate the effect of the national stroke campaign by conducting a
 similar study in 2020 when the campaign has been running for six months.

 Perspectives:

 This study will provide new information about stroke patients and bystanders, their knowledge
 of stroke and their help-seeking behaviour. If more knowledge about the factors that cause
 prehospital delay in stroke treatment are obtained, the investigators will know which areas
 to focus on in the future to improve the outcome for stroke patients. Part of this project
 will examine the effect of TrygFondens national stroke campaign, which is expected to have
 impact on general knowledge and help-seeking behaviour. If more people know the core symptoms
 of stroke, hopefully more people will also know how to react to these symptoms by calling
 EMS. This will eventually increase reperfusion therapy rates, considerably improve stroke
 morbidity and mortality and reduce both individual suffering and the societal costs.
Stroke awareness and help-seeking behaviour: predictors for prehospital delay in stroke
 treatment

 Ane Bull Iversen, MD Section for General Medical Practice Department of Public Health and
 Department of Neurology Department of Clinical Medicine Aarhus University

 Supervisors:

 Professor Bo Christensen, PhD, MD Section for General Medical Practice Department of Public
 Health Aarhus University

 Professor Grethe Andersen, PhD, MD Department of Neurology Department of Clinical Medicine
 Aarhus University

 Senior researcher Morten Bondo Christensen, PhD, MD Research Unit for General Practice
 Department of Public Health Aarhus University

 Professor Søren Paaske Johnsen, PhD, MD Center for Clinical Health Services Research
 Department of Clinical Medicine Aalborg University and Aalborg University Hospital

 Background Stroke is the second-leading cause of death worldwide and a leading cause of
 long-term disability. Each year 12,000 people in Denmark are hit by a stroke. In addition to
 substantial individual suffering, stroke is also associated with considerable costs to
 society.

 The World Health Organization (WHO) has estimated a marked increase in the stroke prevalence
 in 2025 as a result of ageing populations. This development will increase the need to
 identify areas with potential for improvement in the treatment of stroke. Acute reperfusion
 therapies started within 4.5 to 6 hours (in some up to 24 hours) from symptom onset for AIS
 have revolutionized the acute stroke treatment and considerably improved the overall
 prognosis and mortality. However, only 15-25% of Danish patients are eligible to acute
 treatment. This is primarily due to presentation outside the time window for intravenous
 thrombolysis and endo¬vascular treatment at the stroke centre. Time is also of utmost
 importance in patients receiving reperfusions therapies, as the chance of functional
 independence decreases rapidly during the first few hours after stroke onset.

 Numerous attempts have been made to reduce both prehospital and in-hospital delay in stroke
 by educating hospital personal, physicians, emergency medical services (EMS) and the public,
 and by reorganizing stroke centres and EMS systems. Nevertheless, much time is still lost
 before the patient arrives at the hospital. There are many causes for prehospital delay, but
 most are related to patient-dependent factors and not system delay. Many stroke patients do
 not recognize their own symptoms as signs of a stroke, do not understand the severity of
 these symptoms and the importance of contacting EMS immediately. Besides, acute cognitive
 impairment, aphasia and/or hemiplegia makes it difficult to call for medical assistance
 without help from a bystander. Increased prehospital delay can also be caused by
 inappropriate help-seeking behaviour, such as using a private vehicle, visiting a general
 practitioner (GP) or having a wait-and-see attitude.

 Half of the patients and bystanders choose not to contact the EMS, but call their GP or the
 out-of-hours GP instead. Therefore, it is of great importance that persons working with
 telephone triage in these health services (e.g. GPs) recognize stroke symptoms and
 immediately refer the patient to a stroke centre. In a recent German study, GPs generally
 perceived stroke and transient ischemic attack (TIA) as medical emergencies. However, when
 using stroke case scenarios, only two thirds of the patients with clear stroke symptoms were
 referred as a medical emergency.

 Several studies have evaluated the effect of educational campaigns on stroke knowledge and
 help-seeking behaviour. Many of the campaigns have successfully increased the awareness of
 stroke symptoms in the public, but they have had little effect in improving the behavioural
 response; this implies that the higher level of knowledge does not necessary result in
 appropriate actions in the emergency situation. On the other hand, two recent studies found
 an association between number of stroke symptoms correctly reported and the intention to call
 an ambulance. Another study found that the ability to recall two core stroke symptoms (facial
 weakness, limb weakness, or speech problems) was associated with seeking immediate ambulance
 assistance. The few studies that have examined the effect of stroke educational campaigns on
 revascularization therapies and reduced symptom to admission times have had inconsistent
 findings. If future stroke campaigns are to have an impact on the number of patients
 presenting within the reperfusion time window, it is of great importance to have a detailed
 knowledge of the reasons for prehospital delay.

 To our experience, no former studies have systematically collected detailed information about
 stroke knowledge in patients and bystanders and combined these data with a complete
 time-and-event mapping of the prehospital phase for all patients.

 Hypotheses

 1. Prehospital delay in stroke treatment is mainly caused by:

 1. Patient delay: patients and/or bystanders who do not recognize stroke symptoms as
 signs of severe illness that require immediate contact to the emergency medical
 services (EMS).

 2. System delay: low accuracy in telephone triage and the diagnostic process.

 2. National multimedia stroke campaigns can improve the general knowledge of stroke, ensure
 expedient help-seeking behaviour and increase the number of patients calling EMS
 directly.

 Research plan

 Study 1: Characterization of stroke symptom knowledge, help-seeking behaviour and prehospital
 delay in a cohort of consecutive stroke patients and their bystanders (cross sectional
 descriptive study).

 Aims:

 1. To explore the knowledge of stroke in stroke patients and their bystanders.

 2. To explore the process from onset of symptoms until admission to hospital (including
 contact to EMS and/or GP/out-of-hours GP) and the reasons for prehospital delay.

 3. To explore the association between stroke knowledge, help-seeking behaviour and
 receiving revascularization therapy.

 Primary objectives:

 To determine:

 -  The proportion of stroke patients/bystanders knowing at least two core symptoms of
 stroke (defined as facial palsy, palsy of extremities and aphasia/dysarthria).

 -  The proportion of stroke patients/bystanders making a direct EMS call.

 Secondary objectives:

 To determine:

 -  The proportion of stroke patients/bystanders contacting their GP or out-of-hours GP
 in first line.

 -  The proportion of patients contacting a family member or friend in first line.

 -  The average number of stroke symptoms each patient/bystander can identify.

 -  The proportion of patients arriving at hospital within 3 hours of symptom onset
 overall and stratified by whether the patients made a direct EMS call or had
 knowledge of at least to core stroke symptoms.

 -  The proportion of patients receiving revascularization therapy overall and
 stratified by whether the patients made a direct EMS call or had knowledge of at
 least to core stroke symptoms.

 -  Whether stroke characteristics (stroke severity, type of stroke, stroke
 lateralization), medical history with earlier stroke and/or socioeconomic status
 are associated with prehospital delay.

 Method:

 Based on detailed pilot interviews with 30 consecutive stroke patients from The
 Department of Neurology at Aarhus University Hospital, the investigators developed a
 structured interview assessing the knowledge in both the patient and the bystander of
 stroke risk factors, symptoms of stroke and their help-seeking behaviour.

 The interview will be combined with background demographic characteristics and clinical
 information. The investigators will use the patient's medical record (EPJ) and the
 Danish Stroke Register (DSR) to complete this form. Registration of the patient's route
 from onset of symptoms to admission to stroke centre will provide us with a complete
 overview of the timeline.

 For patients arriving by ambulance, the investigators will use the prehospital patient
 journal (PPJ) to document the different phases of prehospital delay. For patients who
 have been in contact with their GP, the GP will receive an electronic questionnaire to
 explore the time- and event pathway from first contact until admitting the patient to
 hospital, alternatively encouraging the patient/ bystander to contact EMS. The GPs will
 be remunerated for returning a completed questionnaire, and the investigators expect a
 response rate of 80%. For patients who have been in contact with the out of-hours GP,
 the investigators will use the out of-hours medical record. Number of contacts to GP,
 out-of-hours GP or EMS will be registered.

 Selection of patients and bystanders:

 All consecutive patients (and bystanders) with AIS, transient ischemic attack (TIA) and
 intracerebral haemorrhage (ICH) admitted to the Department of Neurology and the vascular
 out-patient clinic at Aarhus University Hospital and Regional Hospital West Jutland
 (Holstebro) in the period 28 January 2018 - 10 May 2018 will be interviewed.

 The investigators expect a total of 500 eligible patients and 300 bystanders included
 during the 3-month period. Patients will be interviewed during the acute in-hospital
 stroke phase.

 The bystander is defined as the person who was with the patient, or was called for by
 the patient, when the patient got ill. This is usually a close relative, but can also be
 a friend, college or a nurse in home-nursing. Every effort will be made to interview the
 bystander, either in person or by telephone.

 Inclusion /exclusion criteria: see other section

 Interview:

 The structured interviews will be performed by trained research nurses or a research
 physician from the Department of Neurology, Aarhus University Hospital (AUH), or
 Regional Hospital West Jutland (Holstebro).

 Study 2: Stroke awareness and help-seeking behaviour before and 6 months after
 initiation of a national stroke awareness campaign.

 Aim: To evaluate the immediate effect of the national campaign six months after
 initiation.

 Primary objectives:

 To determine

 -  Whether a stroke campaign has increased the proportion of stroke-patients and
 bystanders making a primary EMS call.

 -  Whether a stroke campaign has increased the proportion of stroke patients,
 bystanders and patients with risk factors of stroke, knowing at least two core
 symptoms of stroke.

 Secondary objectives:

 Objectives from study 1

 Method:

 The national stroke awareness campaign is planned to run in 2019 and 2020 and is
 organized through the network of Danish Council for Resuscitation in collaboration with
 TrygFonden. The TrygFonden supports projects that contribute to better health and safety
 in the Danish population; from first aid courses to research projects. Coinciding this
 campaign Danish Regions have taken initiative to a nationwide networking between the
 pre-hospital organization and acute stroke hospitals in order to increase stroke
 identification by EMS and paramedics and reduce prehospital time-delays.

 This initiative has started in 2017 and will run through 2018 and several years. The
 stroke awareness campaign will therefore run in an optimal situation of collaboration
 between stroke health care professionals and public service.

 The investigators will evaluate the effect of the campaign and optimization of the
 prehospital service by comparing the results from study 1 described above and will
 conduct a similar study in 2020 when the campaign has been running for six months.

 Methodological considerations

 Sample size calculation:

 Study 1 (and 2):

 The sample size calculation is based on data from the pilot study examining stroke
 knowledge and help seeking behavior in patients with acute stroke. The proportion of
 stroke patients (bystanders) who made a direct call to EMS was 40%. To detect a 15 %
 absolute increase in in patients/bystanders making a direct EMS call after a national
 stroke campaign, at a power of 80% and a significance level of 5%, a sample size of at
 least 346 will be required. To account for patients with pre-stroke modified Rankin
 Scale (mRS) ≥ 3, patients who cannot be reached and patients/bystanders not willing to
 participate the investigators therefore plan to include 500 patients and 300 bystanders.

 Planned statistical analyses:

 Cohort characteristics are summarized using percentages or medians and interquartile
 range (Q1-Q3) as appropriate. Data with non-normal distributions and/or with unequal
 variance are compared using the Mann-Whitney U-test. In addition, comparisons will be
 made using multivariable linear and binary regression with adjustment for potential
 confounding factors.

 Data handling and records:

 All study data will be recorded in an electronic Case Report Form (REDCap) with
 identification via a study identification number. The study will be governed by the
 rules and regulations laid down in the Danish Act on Processing of Personal Data.
 Approval is obtained from the Danish Data Protection Agency. No personal data will be
 shared with any foreign countries.

 Patient participation will be recorded in the medical record. Data will be deleted after
 15 years.

 Feasibility The PhD-fellow, M.D. Ane Bull Iversen (ABI) will be part of "acute
 conditions" - group led by Senior researcher, GP, PhD Morten Bondo Christensen at the
 Research Unit for General Practice, Department of Public Health, Aarhus University,
 where also the main supervisor Professor, GP, PhD Bo Christensen is employed. The group
 and the academic environment possess the required expertise in general practice
 medicine, epidemiology, data management and biostatistics to fully support this project
 during the entire PhD programme.

 ABI will be employed at the Department of Neurology, Aarhus University Hospital, where
 co-supervisor Grethe Andersen is professor and head of the Danish Stroke Center.
 Co-supervisor Søren Paaske Johnsen is professor at the Department of Clinical Medicine,
 Aalborg University and Aalborg University Hospital.

 ABI will be responsible for the development and the execution of the structured
 interviews and questionnaires and cooperation with other departments. She will also be
 responsible for the data collection and the data analysis. In addition to writing her
 PhD thesis, she will also be responsible for writing the first drafts and the final
 versions of all papers.

 ABI is a medical doctor in residency for general practice. She has obtained clinical
 experience with general practice through 18 months of specialty training in general
 medicine.

 Ethics and approvals Approval is obtained from the Danish Data Protection Agency and the
 Multipractice Study Committee of the Danish College of General Practitioners. Approval
 from The Central Denmark Region Committees on Health Research Ethics is not necessary.

 Economy A grant from TrygFonden will cover most of the salary for the PhD-fellow and for
 part-time research nurses during the three-year period. The research group has received
 a grant from the Committee for Quality Improvement and Continuing Medical Education in
 general practice in the Central Denmark Regions and the Multipractice Study Committee of
 the Danish College of General Practitioners. (The latest to compensate participating GPs
 for answering the questionnaire).

 Publication policy The results of the study, both negative, inconclusive and positive,
 will be disseminated as widely as possible. This will take place through publication of
 scientific papers in international peer-reviewed journals, conference presentations and
 press releases (if relevant).

 Perspectives This study will provide new information about stroke patients, bystanders
 and persons at high risk of getting a stroke, their knowledge on stroke and their
 help-seeking behaviour. If more knowledge about the factors that cause prehospital delay
 in stroke treatment are obtained, the investigators will also know which areas to focus
 on in the future to improve the outcome for stroke patients.

 Part of this project will examine the effect of TrygFondens national stroke campaign,
 which is expected to have impact on general knowledge and help-seeking behaviour. If
 more people know about the core symptoms of stroke, more people will also know how to
 react to these symptoms by calling EMS which will eventually increase reperfusion
 therapy rates. This is expected to considerably improve stroke morbidity and mortality
 and to reduce both the individual suffering and the societal costs.
Inclusion Criteria:

 -  Diagnosed with AIS, TIA or ICH

 -  Admitted to the Department of Neurology at Aarhus University Hospital or Regional
 Hospital West Jutland (Holstebro)

 -  Age ≥ 18 years

 -  Onset of symptoms ≤ 7 days before time of interview

 Exclusion Criteria:

 -  Modified Rankin Scale (mRS) ≥ 3* (pre-stroke)

 -  Transferred from other regions in Denmark or abroad

 -  Not willing to participate in the study

 -  Cannot be reached ("out of office")

 -  Non-Danish speaking