PhD-student
Mette Munk Lauridsen
Research Unit for Gatroenterology and Hepatology, Odense University Hospital
| Project management | ||
| Project status | Closed | |
| Data collection dates | ||
| Start | 12.08.2013 | |
| End | 31.10.2015 | |
Diagnosing Minimal Hepatic Encephalopathy using continous reaction time measurements
Short summary
A clinical study comprised of 3 sub-studies all focusing on how we can find hepatic encephalopathy before it requires hospital admission. We use to different psychometric methods in the study: A computerized continuous reaction time measurement and a paper-pencil test battery. The latter serves as a reference test and our primary focus is thus on validating the use of the continuous reaction time test, which is faster and simpler than the paper pencil test. We have included 135 patients with liver cirrhosis and 100 healthy controls. Apart form cognitive function we measured quality of life, graded comorbidity and liver disease severity.
Rationale
Liver cirrhosis is, in more than 50 % of cases, complicated by hepatic encephalopathy (HE). The earliest and subclinical form of HE is called minimal HE. Patients with minimal HE have poor quality of life, increased risk of falls, traffic accidents, overt HE and have a poor prognosis. Minimal HE can, in most cases, be treated with ammonium lowering agents such as lactulose. By definition, covert HE is unrecognizable at physical evaluation and must be diagnosed via sensitive psychometric methods. There are several available on the marked. This PhD project will lay the grounds for a rational and evidences based approach to managing minimal HE in daily clinic at OUH and in Denmark. Our project primarily focuses on the possibility of diagnosing hepatic encephalopathy by means of a computerized method called CRT - continuous reaction time measurements. In Denmark we have a longstanding tradition for using this test.
The main aim is to validate the CRT method in a healthy population (n=100) and in cirrhosis patients (n=120). Sensitivity and specificity will be assessed by a comparison between the CRT method and the closest we get to and gold standards, namely the PSE test - an old fashioned and time-consuming paper pencil test. The tests ability to detect a treatment response will be tested by giving 44 patients placebo or rifaximin, lactulose and branched chain amino acids. PhD student Mette Munk Lauridsen has visited the developers of the test, a highly esteemed research group lead by Professor Karin Weissenborn, at Medizinischer Hochschule Hannover in December 2012.
Description of the cohort
We have included 100 adult healthy men and women with different educational backgrounds and 135 patients with liver cirrhosis, men age 55 years, 173 are women, the cirrhosis aetiology is alcohol in 95%.
Data and biological material
Continuous reaction time measurements (CRT)
Use is based on studies showing that high intra-individual variability in response times can distinguish patients with hepatic encephalopathy in patients with chronic organic brain damage (Elsass 1981, Elsass 1984, Elsass 1985, Elsass 1986). CRT method's major advantages is that it is quick to perform, the principle of the study is easy for the patient and physician to understand that interpretation is simple and does not require the patient to have computer skills. This does not apply to the other 3-4 computer-based diagnostic tests developed abroad. The test is performed via a laptop which Ekho software available (Bitmatic, Aarhus). The entire test takes 10 minutes which time the instruction should be - ie. a total of approx. 10 minutes.
Porto Systemic Encephalopathy test (PSE) test
Paper-pencil test battery. Duration approx. 30 minutes. Test manual has been translated into Danish of project officers with the permission of the International Society for hepatic encephalopathy and nitrogen metabolism (ISHEN), right-holder. The test consists of 5 sub tests. In particular interpretation of line test can cause problems. It is proposed therefore to visit K. Weiss Born in Hannover, which is co-developer of the test, a view training in the proper use of the test. The result of the PSE test the psychometric hepatic encephalopathy score (PHES). Try controllers and a few trained research assistants perform the study.
Charlson Score: Charlson score or Charlson index is a comorbidities index that predicts 10-year mortality in patients with multiple competing disorders. Each chronic illness recorded and given a point value depending on how deadly the disease is. The patient fills itself or with the help of a questionnaire which asked for 19 disease categories. The higher Charlson index the poorer the prognosis.
Blood tests: All chronically ill controls get the consent measured liver enzymes at normal temperature. Blood test for that anyway blood samples for their usual outpatient follow-up.
Statistics: Results from CRT method and PSE used to calculate sensitivity and specificity and PPV and NPV as the gold standard for the diagnosis of MHE is assumed to be PSE. Possibly, covariates of interest (eg. gender, age, other diagnoses) may want.
Quality of Life Score
Sickness Impact profile (SIP) questionnaire is a study of MHE shown to detect a treatment response. SIP provides a measure of perceived health status, which is sensitive enough to detect changes or differences in health status that occur over time or between groups. SIP is a functional status of instrument, consisting of 136 statements that describe the disease-related behavioural disorders. Handling time is stated to be between 20-30 minutes by interviewing management (Bergner 1981). If there is any doubt about whether the patient is able to read and understand the many questions that reveal the quality of life in 12 areas, the patient should be guided through filling out the form. Try controllers and a trained research assistant perform the study.
SF-36: A questionnaire that patients can fill or can be filled via an interviewer. Operation time about 20 min.
MMSE
MMSE contains a series of short, simple tasks to illustrate eight different types of cognitive functions. Performance scores and summed into a raw score ranging from 0 - 30, where 30 represents the 'best' (flawless) performance. MMSE was originally developed to measure cognitive skills in a broad sense in the elderly and to record any changes in cognitive functioning over time, but MMSE is not specifically designed to identify signs of dementia. The test included in this study to test patients' orientation in time and place and to screen for memory problems. Handling time approximately 10 minutes.
Collaborating researchers and departments
Medical Department of Hepatology and Gastroenterology, Aarhus University Hospital
- Professor Hendrik Vilstrup
Medical Department, Hospital of South West Jutland
- Jeppe Gram, PhD
- Torben Knudsen, DMSc
Publications associated with the project