PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).
EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.
KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.
CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.
DESIGN: Cross-sectional survey.
SETTING: Community, 22 countries including all World Health Organization regions.
PARTICIPANTS: Persons (N=12,591) with traumatic or nontraumatic SCI aged 18 years or older.
INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: We estimated the prevalence of problems in 53 areas of functioning from the Brief International Classification of Functioning, Disability and Health (ICF) core set for SCI, long-term context, or ICF rehabilitation set covering 4 domains: impairments in body functions, impairments in mental functions, independence in performing activities, and restrictions in participation. Associations between areas of functioning were identified and visualized using conditional independence graphs.
RESULTS: Participants had a median age of 52 years, 73% were male, and 63% had paraplegia. Feeling tired, bowel dysfunction, sexual functions, spasticity, pain, carrying out daily routine, doing housework, getting up off the floor from lying on the back, pushing open a heavy door, and standing unsupported had the highest prevalence of problems (>70%). Clustering of associations within the 4 functioning domains was found, with the highest numbers of associations within impairments in mental functions. For the whole International Spinal Cord Injury sample, areas with the highest numbers of associations were circulatory problems, transferring bed-wheelchair, and toileting, while for the World Health Organization European and Western Pacific regions, these were dressing upper body, transferring bed-wheelchair, handling stress, feeling downhearted and depressed, and feeling happy.
CONCLUSIONS: In each domain of functioning, high prevalence of problems and high connectivity of areas of functioning were identified. The understanding of problems and the identification of potential targets for intervention can inform decision makers at all levels of the health system aiming to improve the situation of people living with SCI.