The clinical course of low back pain: a meta-analysis comparing outcomes in randomised clinical trials (RCTs) and observational studies.

BACKGROUND: Evidence suggests that the course of low back pain (LBP) symptoms in randomised clinical trials (RCTs) follows a pattern of large improvement regardless of the type of treatment. A similar pattern was independently observed in observational studies. However, there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials. To test this assumption, the aim of our study was to compare the course of LBP in RCTs and observational studies. METHODS: Source of studies CENTRAL database for RCTs and MEDLINE, CINAHL, EMBASE and hand search of systematic reviews for cohort studies. Studies include individuals aged 18 or over, and concern non-specific LBP. Trials had to concern primary care treatments. Data were extracted on pain intensity. Meta-regression analysis was used to compare the pooled within-group change in pain in RCTs with that in cohort studies calculated as the standardised mean change (SMC). RESULTS: 70 RCTs and 19 cohort studies were included, out of 1134 and 653 identified respectively. LBP symptoms followed a similar course in RCTs and cohort studies: a rapid improvement in the first 6 weeks followed by a smaller further improvement until 52 weeks. There was no statistically significant difference in pooled SMC between RCTs and cohort studies at any time point:- 6 weeks: RCTs: SMC 1.0 (95% CI 0.9 to 1.0) and cohorts 1.2 (0.7to 1.7); 13 weeks: RCTs 1.2 (1.1 to 1.3) and cohorts 1.0 (0.8 to 1.3); 27 weeks: RCTs 1.1 (1.0 to 1.2) and cohorts 1.2 (0.8 to 1.7); 52 weeks: RCTs 0.9 (0.8 to 1.0) and cohorts 1.1 (0.8 to 1.6). CONCLUSIONS: The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies. In addition to a shared 'natural history', enrolment of LBP patients in clinical studies is likely to provoke responses that reflect the nonspecific effects of seeking and receiving care, independent of the study design

Structural studies of neuropilin-1

Neuropilin-1 (Nrp1) is ~130kDa multidomain type I transmembrane protein with no intrinsic enzymatic activity. Instead, acting as co-receptor in conjunction with other membrane proteins such as vascular endothelial growth factor receptors VEGFRs and plexins, neuropilins regulate key processes in vasculogenesis and neuronal cell development. The functional flexibility of neuropilins can be attributed to their multidomain composition. NRPs contain five extracellular domains: two CUB domains (homologous to complement binding factors) labelled a1 and a2; two coagulation factor domains, labelled b1 and b2, with homology to C1/C2 domains of factor FV/VIII; and a membrane-proximal MAM (meprin/antigen 5/ receptor tyrosine phosphotase μ) domain, labelled c. The cytoplasmic portion of a neuropilin molecule, comprises a small 44 residue-long domain that is structurally uncharacterized. Most research efforts have focused on the extracellular ligand binding a1a2b1b2 domains. This thesis will describe my PhD work which has focused on structural determination of the two poorly characterized domains of human neuropilin-1: MAM (c) domain - believed to be required for neuropilin dimerization, and the short cytoplasmic domain which is linked to VEGF signalling, NRP1 recycling, association with PDZ domain-containing intracellular proteins, and blood vessels permeability. This work utilised a variety of complimentary techniques including x-ray crystallography, NMR, ITC and CD shedding light on how these domains carry out their biological function. Furthermore, the potential medical significance of Nrp1 means that it is a valid anti-cancer therapeutic target. A number of co-crystallised structures are presented of the b1 domain in complex with small ligands in an on-going drug development collaboration with an industry partner

Predictive ability of a modified Örebro Musculoskeletal Pain Questionnaire in an acute/subacute low back pain working population

The original ‘Örebro Musculoskeletal Pain Questionnaire’ (original-ÖMPQ) has been shown to have limitations in practicality, factor structure, face and content validity. This study addressed these concerns by modifying its content producing the ‘Örebro Musculoskeletal Screening Questionnaire’ (ÖMSQ). The ÖMSQ and original-ÖMPQ were tested concurrently in acute/subacute low back pain working populations (pilot n = 44, main n = 106). The ÖMSQ showed improved face and content validity, which broadened potential application, and improved practicality with two-thirds less missing responses. High reliability (0.975, p < 0.05, ICC: 2.1), criterion validity (Spearman’s r = 0.97) and internal consistency (α = 0.84) were achieved, as were predictive ability cut-off scores from ROC curves (112–120 ÖMSQ-points), statistically different ÖMSQ scores (p < 0.001) for each outcome trait, and a strong correlation with recovery time (Spearman’s, r = 0.71). The six-component factor structure reflected the constructs originally proposed. The ÖMSQ can be substituted for the original-ÖMPQ in this population. Further research will assess its applicability in broader populations