The use of cerebrospinal fluid in biomarker studies.

Cerebrospinal fluid (CSF) is an extremely useful matrix for biomarker research for several purposes, such as diagnosis, prognosis, monitoring, and identification of prominent leads in pathways of neurologic diseases. Such biomarkers can be identified based on a priori hypotheses around prominent protein changes, but also by applying -omics technologies. Proteomics is widely used, but metabolomics and transcriptomics are rapidly revealing their potential for CSF studies. The basis of such studies is the availability of high-quality biobanks. Furthermore, profound knowledge and consequent optimization of all aspects in biomarker development are needed. Here we discuss current knowledge and recently developed protocols for successful biomarker studies, from collection of CSF by lumbar puncture, processing, and biobanking protocols, preanalytic confounding factors, and cost-efficient development and validation of assays for implementation into clinical practice or research.

Orthotic devices for treating patellofemoral pain syndrome.

BACKGROUND: Patellofemoral pain syndrome is a frequently reported condition in active adults. A wide variety of conservative treatment strategies have been described. As yet, no optimal strategy has been identified. Application of orthotic devices e.g. knee braces, knee straps, forms of taping of the knee, active training devices, knee sleeves and in-shoe orthotics to support the foot have been advocated to treat this condition. OBJECTIVES: To assess the effectiveness of foot and knee orthotics for treatment of patellofemoral pain syndrome. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (December 2001), the Cochrane Controlled Trials register (Issue 2, 2000), MEDLINE (January 1966 to March 2000; EMBASE (January 1988 to March 2000); CINAHL (January 1982 to March 2000) and PEDro (up to March 2000). Relevant orthotic companies were contacted. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing the effectiveness of knee or foot orthotics for treatment of patellofemoral pain syndrome were selected. Trials describing the use of orthotic devices in conjunction with operative treatment were excluded. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed methodological quality of the identified trials by use of a modified version of the Cochrane Musculoskeletal Injuries Group assessment tool, consisting 11 items. Two reviewers extracted data without blinding. Trialists were contacted to obtain missing data. MAIN RESULTS: Five trials involving 362 participants were included in this review. Five other trials await possible inclusion if further information can be obtained and one awaits further assessment. Due to clinical heterogeneity, we refrained from statistical pooling and conducted analysis by grading the strength of scientific evidence. The level of obtained research-based evidence was graded as limited as all trials were of low methodological quality. This limited research-based evidence showed the Protonics orthosis at six week follow-up was significantly more effective for decrease in pain (weighted mean difference (WMD) between groups 3.2; 95% confidence interval (CI) 2.8 to 3.6), functional improvement on the Kujala score (WMD 45.6; 95% CI 43.4 to 47.7) and change in patellofemoral congruence angle (WMD 17.2; 95% CI 14.1 to 20.3) when compared to no treatment. A comprehensive programme including tape application was significantly superior to a monitored exercise programme without tape application for decrease in worst pain (WMD 1.6; 95% CI 0.4 to 2.8) and usual pain (WMD 1.2; 95% CI 0.2 to 2.1), and clinical change and functional improvement questionnaire scores (WMD 10, 95% CI 2.07 to 17.93) at four weeks follow-up. The trials reported statistically significant differences in patient satisfaction after applied therapy (WMD 3.3; 95% CI 0.5 to 6.1) in favour of the McConnell regimen compared with the Coumans bandage at six weeks follow-up. REVIEWER'S CONCLUSIONS: The evidence from randomised controlled trials is currently too limited to draw definitive conclusions about the use of knee and foot orthotics for the treatment of patellofemoral pain. Future high quality trials in this field are warranted.