Functional, Cognitive and Emotional Outcomes After Transient Ischemic Attack: a Prospective

Functional, cognitive and emotional outcomes after Transient Ischemic Attack: A prospective, controlled cohort study to inform future rehabilitative interventions

Protocol Version 2: Dated 30th March 2010

1. Management Team

Chief Investigator:

Professor Catherine Sackley

Professor of Physiotherapy

Primary care Clinical Sciences

University of Birmingham

B15 2TT

Tel: 0121 414 4198

Miss Nicola Brittle
Research assistant/PhD student
Primary care Clinical Sciences
University of Birmingham
B15 2TT
Tel: 0121 414 5483
/ Mr Roger Holder
Head of statistics/Senior lecturer
Primary care Clinical Sciences
University of Birmingham
B15 2TT
Tel: 0121 414 6368
/ Mrs Sheila Bailey
Project officer
Primary care Clinical Sciences
University of Birmingham
B15 2TT
Tel: 0121 414 7956

Professor Richard McManus
Professor of Primary Care Cardiovascular Research and Honorary Consultant
Primary Care Clinical Sciences
University of Birmingham
B15 2TT
Tel: 0121 414 2658
/ Dr Daniel Lasserson
Clinical Lecturer and GP
Public Health and Primary Care
University of Oxford
OX3 7LF
/ Ms Amunpreet Boyal
Research Nurse
Primary care Clinical Sciences
University of Birmingham
B15 2TT
Tel: 0121 414 8172

Professor Jonathan Mant
Professor of Primary Care Research
General Practice & Primary Care
University of Cambridge
CB2 0SR
Tel: 01223 330325
/ Ms Carron Sintler
Consultant Physiotherapist for Stroke Services
University Hospitals Birmingham NHS Foundation Trust
Selly Oak Hospital
B28 6JD
/ Dr Dawn Swancutt
Project Manager
Primary Care Clinical Sciences
University of Birmingham
B15 2TT
Tel: 0121 414

2. Steering Committee

Management Team

Patient representative

3. Lay Summary

The neurological symptoms associated with Transient Ischemic Attack (TIA), also known as mini-stroke, should persist for no longer than 24 hours. However little is known about the long term impact of TIA on patient reported outcomes such as mood, quality of life and return to usual activities/social life.

The aim of this study is to investigate whether or not patients have depressed mood, and/or residual functional or cognitive problems that adversely influence their day to day living, after being diagnosed with TIA. The study will also examine the costs associated with TIA, including personal economic losses e.g. time off work due to illness, and health and social care service provision.

The following three study groups will be monitored over a 12 month period:

·  Patients attending TIA clinics, diagnosed with first ever TIA (group A)

·  Patients attending TIA clinic diagnosed as NOT having had a TIA or stroke (group B)

·  Healthy controls from GP registers (group C)

In total we aim to recruit 600 individuals from NHS trusts throughout the West Midlands.

Questionnaires assessing function, mood and service use (the impact of TIA on the NHS and society) will be mailed out to participants at 0, 3, 6 and 12 months. A subset of the study population will also undergo cognitive screening (an assessment of mental processing). The data collected will invariably inform future trial design, providing information such as suitability of outcome measures.

4. Background

Transient Ischemic Attack (TIA) affects a huge proportion of the population. When standardised to the 2005 population of England, the annual incidence rate of probable and definite TIA was 1.08 (0.95–1.21) per thousand, which translates into approximately 54,610 individuals experiencing their first TIA in that year alone 1. National stroke guidelines and audits 2 recommend that people with a suspected TIA or minor stroke are referred to a TIA clinic and managed according to their risk of further stroke. It is suggested that there were approximately 150,000 new referrals to TIA clinics in England in 2005 1. This estimate includes patients with definite, probable and suspected TIA, of which incident-definite TIAs are thought to account for only about 18% of referrals.

Compared to the wealth of literature available on stroke there is relatively little follow-up data available on TIA and, where there is data, the emphasis tends to be on medical management and survival. Success with this group appears to be measured by time from event to clinic, prescription of prophylactic medications and prevention of further cardiovascular episodes and/or death. The World Health Organisation defines health “a state of complete physical, mental and social well-being and not merely the absence of diseases and infirmity”, but despite this little attention has been given to the effects of TIA on functional and psychosocial outcomes, and rehabilitation needs. With increased recognition that healthcare evaluations should incorporate patients’ perspectives, research needs to include self-report health rating scales as well as the inherent survival statistics and referral times 3.

The few studies to date that have included self-report measures suggest that following TIA, people experience prolonged functional impairments that can adversely influence their health, well being and activity levels. A study in Germany by Daffertshofer et al 4 followed up patients with both stroke and TIA and found that after six months 17% of their TIA patients were ‘dependent’. The results are of greater concern considering that the study sample had been hospitalised and, it might be argued, had access to more services than those in the community. In the OXVASC study 5, patients with TIA did not return to their normal levels of functional performance in activities of daily living. Almost a third of the sample reported having restricted function after TIA, as measured by the Nottingham Extended ADL scale.

5. Objectives

a) To investigate whether patients have depressed mood, and/or residual functional or cognitive problems that adversely influence their day to day living, after being diagnosed with TIA?

b) To investigate whether any other factors (e.g. age, gender, concurrent medical conditions) influence patient outcomes after TIA

c) To investigate the impact of TIA on the NHS and society e.g. Use of health and social care services, living situation and personal economic losses, including time off work due to illness

This work has been identified as a priority by the Stroke Network Rehabilitation and Primary Care Clinical Studies Groups and fits with the Birmingham and Black Country NIHR Collaborations for Leadership in the Applied Health Research and Care programme. This area of investigation is also recognised as important by service users; Quote, “Evidence I am aware of from stroke survivors whom I come into contact with in my social work practice would indicate that TIA or minor stroke can cause significant and lasting deficits physically, cognitively and emotionally”.

The data collected will inform trial design, providing information such as suitability of outcome measures. It is also hoped that the results can be used to assess the need for, and possible development of rehabilitative/preventative interventions.

6. Trial Design

6.1 Design

Prospective cohort study with two control groups

6.2 Setting

TIA clinics and GP practices in the West Midlands

6.3 Participants

We propose to monitor three groups longitudinally:

1. People attending TIA clinics diagnosed with a TIA (group A)
2. People attending TIA clinic diagnosed as NOT having had a TIA or stroke (group B)
3. Age and postcode matched controls from GP registers (group C)

7. Eligibility

7.1 Inclusion Criteria

Group A:

1. Diagnosis of TIA confirmed by consultant stroke physician or neurologist at the TIA clinic
2. Diagnosis made within 14 days of event
3. New episode (not follow-up appointment)
4. Patient deemed by consultant stroke physician or neurologist to be able to self-complete postal questionnaires (no severe cognitive impairment)

Group B:

1. Diagnosed as not having had a TIA or stroke by consultant stroke physician or neurologist at the TIA clinic
2. Diagnosis made within 14 days of event
3. New episode (not follow-up appointment)
4. Patient deemed by consultant stroke physician or neurologist to be able to self-complete postal questionnaires (no severe cognitive impairment)

Group C:

1. No known severe cognitive impairment that would prohibit self-completion of postal questionnaires (screen through MidReC/PCRN)

7.2 Exclusion Criteria (all groups)

1. Past medical history of stroke/TIA

7.3 Rational for choices

To rule out inappropriate referrals, patients diagnosed after 14 days of their event will not be included in the study. Patients attending follow-up appointments will also be rejected to avoid repetition of data collection, as will those with severe cognitive impairment to minimize the amount of incomplete data returned via postal questionnaires. To increase recruitment rates and therefore achieve a more representative sample, consent will be sought at TIA clinic appointments.

7.4 Defining the boundary between stroke and TIA:

TIA was traditionally defined as, “a sudden, focal neurologic deficit that lasts for less than 24 hours, is presumed to be of vascular origin, and is confined to an area of the brain or eye perfused by a specific artery” 6. This arbitrary 24-hour threshold has since been refuted 6; 7. The likelihood that symptoms will resolve completely within 24 hours was shown to be less than 15 percent if symptoms lasted more than 1 hour 8. Advances in diagnostic imaging have also demonstrated an inconsistency with the concept of TIA (ischemia causing transient symptoms but no infarction) and clinical diagnosis. A pooled analysis of Diffusion-weighted MRI (DWI)-studied patients revealed brain infarction in a clinically relevant location in approximately one third of patients with the 24-hour diagnosis of TIA 9. The median duration of symptoms was longer among patients with DWI abnormality than those without DWI abnormality suggesting that stroke and TIA form a continuum rather than distinct entities of cerebrovascular disease. Following such revelations, a shift from arbitrary definitions of TIA to tissue-based definitions has been proposed, e.g. “a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction” 6

In current practice brain imaging is not routinely available for diagnosing TIA. Consequently if we only adopted the reformed definition of TIA our results would not be pertinent in the present climate. Although we acknowledge that the reliability of diagnoses can be improved with MRI, including DWI, we will rely on the professional judgement of consultant stroke physicians or neurologists at participating TIA clinics to diagnose participants. The outcome of investigations including diagnostic imaging will be reported to help describe any covariance in the results however; as such investigations are not routinely available to all patients they will not be used as the basis of diagnosis.

8. Recruitment

Groups A and B will be identified by consultant stroke physicians or neurologists at participating TIA clinics. Consecutive patients will be told about the study invited to participate if they are judged by their consultant/neurologist to meet the selection criteria.

Potential healthy controls (group C) will be identified from GP systems with the help of the Midlands General Practice Consortium (MidReC) and the Primary Care Research Network (PCRN). GP practices will send out information to patients who are not on their TIA/stroke register and who are suitable age/gender/postcode matches for participants in group A.

9. Consent

A member of the research team will be available at participating TIA clinics to answer any questions and gain consent from those keen to participate. As the study is not experimental and will not impact on usual treatment in any way, participants in groups A and B will be asked to consent at their clinic appointment. We feel that this will give us a more representative sample of patients owing to consecutive recruitment. Each participant will be given an information sheet with details about study, rights to withdraw consent at any stage, and contact details for the research team (should they have any queries about the study after leaving the clinic). A copy of the Participant information sheet and consent form can be found in appendix 1 and 2 respectively.

By definition, TIA is a minor vascular event; therefore potential participants should not have impaired capacity to participate.

Individuals recruited via GP practices will receive participant information and consent forms by post with prepaid return envelope. They will therefore have longer to decide whether or not to accept the invitation to participate in the study. As with groups A and B, a contact telephone number will be provided, allowing patients the opportunity to ask questions pertaining to the study. If individuals have not responded within three months, it will be assumed that they do not wish to participate.

Patients in Groups A and B will be given the opportunity to consent to i) completing postal questionnaires only, or ii) completing both postal questionnaires and cognitive screening; a one hour face-to-face assessment with a trained assessor. The minimum level of consent required by participants in the control group will be determined by the level of consent given by their respective age/gender/postcode match in group A. The consent form sent to participants in group C will reflect this. For example, if someone in group A consents to questionnaires and cognitive screening, their matched control must also consent to both.

As part of the consent process, permission will be sought from the research participants to inform their GP that they are taking part in the study. A copy of the letter that will be sent out to inform GPs of their patient’s participation can be found in appendix 3.

10. Data sources/measurement

Outcome measures have been chosen based on their content and psychometric properties for use in stroke and/or elderly populations. Assessments will be conducted at 0 (baseline), 3, 6 and 12 months after diagnoses (or after consent with respect to the healthy control group). Data will be collected from medical records (M), postal questionnaires (P) and direct contact (D). Information that is missing from postal returns will be followed up by telephone interview.

10.1 Baseline assessment (M)

Data will be extracted from TIA clinic assessment forms (groups A and B) or GP databases (group C). Data will be collected on demographics, social history, past medical history and, for groups A and B, details of the presenting condition, investigations and medical management. The proposed data collection form has been informed by preliminary liaison with TIA clinics in the West Midlands. Discussions will be held with participating clinics to ensure these data form part of the routine assessment.

10.2 Outcome measures/assessment tools

1. Nottingham Extended ADL Scale (P) 10. A self-report measure of higher functional self-care independence.
2. Hospital Anxiety and Depression Scale (P) 11. A self-assessment scale, found to perform well in assessing severity and caseness of anxiety disorders and depression in both somatic and psychiatric cases and, not only in hospital practice for which it was first designed, in primary care patients and the general population.
3. Client service receipt inventory (P) 12. A questionnaire designed to aid economic analysis, yielding information on use of health and social care services, other economic impacts (such as time off work due to illness) and socio-demographic information. Although originally designed for use in mental health, the CSRI has been used in over 150 health and social care economic evaluations, each time being tailored to suit the data requirements for individual studies.
4. Birmingham University cognitive screen (D): 13. A measure of cognition (language, memory, perception and attention), using a series of simple tasks. The assessment takes approximately one hour to administer by trained assessor. Due to resources/logistics BUCS will only be done in a subset of the study population (random sample of group A and C, at 2 time points only).
5. Cardiovascular risk factors: Smoking, alcohol, exercise as measured by: International physical activities questionnaire-short form 14.

10.3 Clinical End points: