Cognitive and Blood Biomarker Assessment After CO Exposure

Study Overview
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Brief Summary
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Carbon monoxide (CO) is reported to cause around 30 deaths, 200 admissions and 4000 presentations to Emergency Departments each year in the UK. In the longer term, CO poisoning is recognised to cause persistent neurological problems (including impairments of thinking and behavioural changes), which can develop days to weeks after the initial exposure. However, the incidence of these long-term sequelae is unknown. In addition, there is evidence of long-lasting inflammatory changes in the brain and on-going brain cell injury, although how long this persists is also unknown. Initial assessments of CO exposure can be unreliable if blood tests are not carried out within a relatively short period after the exposure and other biomarkers (such as imaging) are insensitive to detecting previous CO exposure. Certain proteins that are found in brain cells can be detected in the blood of individuals following brain injury and brain cell death. These proteins have been found to be raised in the acute period after minor head injury, persistently raised in patients with a traumatic brain injury and evidence of on going neurodegeneration (i.e. on going brain cell death) and in patients with various types of dementia. The investigators will assess the presence of these proteins in the blood of 50 participants with proven CO exposure in the sub-acute to chronic timescale (2 weeks to 2 years). This has not been done before and will allow assessment of the presence of on going brain injury in these participants. The investigators will also assess cognitive (e.g. memory, attention and speed of thinking) and behavioural impairments in these participants to help characterise the common impairments suffered following CO exposure and relate these to evidence of persistent brain injury and severity of CO exposure.

Official Title
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Cognitive, Behavioural and Blood Biomarker Assessment After Carbon Monoxide (CO) Exposure

Conditions
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Carbon Monoxide Poisoning

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals identified as having confirmed exposure to CO between 2 weeks to 2 years at time of assessment. CO exposure determined by either; documented COHb levels above 1.6% in non-smokers and above 6.3% in smokers. or, individuals with evidence of being exposed to raised levels of CO and symptoms Exclusion Criteria: age <18 years actual or suspected smoke inhalation significant neurological or psychiatric illness prior to CO exposure inability to provide consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Carbon monoxide exposure<br>Confirmed exposure to carbon monoxide | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood biomarker level of neurofilament light in participants with proven CO exposure. | Plasma levels of neurofilament light will be measured | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood biomarker level of tau in participants with proven CO exposure. | Plasma levels of tau will be measured | 18 months | 
| Blood biomarker level of glial fibrillary acidic protein in participants with proven CO exposure. | Plasma levels of glial fibrillary acidic protein will be measured | 18 months | 
| Behavioural questionnaire: depression (Patient Health Questionnaire - part 9) | Participants will be asked to complete a validated questionnaire assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Behavioural questionnaire: anxiety (Generalised Anxiety Disorder Questionnaire - GAD7) | Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Behavioural questionnaire: post-traumatic stress symptoms (Impact of Events Scale) | Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Behavioural questionnaire: Attentional behaviour (Rating Scale of Attentional Behaviour) | Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Behavioural questionnaire: fatigue (Visual Analogue Scale of Fatigue) | Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Behavioural questionnaire: Quality of life (The Short Form (36) Health Survey) | Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Behavioural questionnaire: return to work/social activities (Work and Social Adjustment Scale) | Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score. | 18 months | 
| Cognitive assessment | Participants will complete a battery of cognitive assessments with a large normative control population. Cognitive tests will assess speed of information processing, reasoning, memory and visuospatial abilities. All results will be a numerical result. | 18 months |