Clinical decision rule for primary care patient with acute low back pain at risk of developing chronic pain

Background context Primary care clinicians need to identify candidates for early interventions to prevent patients with acute pain from developing chronic pain. Purpose We conducted a 2-year prospective cohort study of risk factors for the progression to chronic pain and developed and internally validated a clinical decision rule (CDR) that stratifies patients into low-, medium-, and high-risk groups for chronic pain. Study design/Setting This is a prospective cohort study in primary care. Patient sample Patients with acute low back pain (LBP, ≤30 days duration) were included. Outcome measures Outcome measures were self-reported perceived nonrecovery and chronic pain. Methods Patients were surveyed at baseline, 6 months, and 2 years. We conducted bivariate and multivariate regression analyses of demographic, clinical, and psychosocial variables for chronic pain outcomes, developed a CDR, and assessed its performance by calculating the bootstrapped areas under the receiver-operating characteristic curve (AUC) and likelihood ratios. Results Six hundred five patients enrolled: 13% had chronic pain at 6 months and 19% at 2 years. An eight-item CDR was most parsimonious for classifying patients into three risk levels. Bootstrapped AUC was 0.76 (0.70-0.82) for the 6-month CDR. Each 10-point score increase (60-point range) was associated with an odds ratio of 11.1 (10.8-11.4) for developing chronic pain. Using a less than 5% probability of chronic pain as the cutoff for low risk and a greater than 40% probability for high risk, likelihood ratios were 0.26 (0.14-0.48) and 4.4 (3.0-6.3) for these groups, respectively. Conclusions A CDR was developed that may help primary care clinicians classify patients with strictly defined acute LBP into low-, moderate-, and high-risk groups for developing chronic pain and performed acceptably in 1,000 bootstrapped replications. Validation in a separate sample is needed

Validation of the Repetitive Behavior Scale-Revised in Spanish-Speakers Participants with Autism Spectrum Disorder

Restricted and repetitive behavior (RRB) is one of the two key diagnostic features of autism spectrum disorder (ASD). DSM-5 highlights the importance of severitybased diagnostic modifiers assigned on the basis of intensity of needed supports. Therefore, there is a need for available measures that assess the severity of RRB. The repetitive behavior scale-revised (RBS-R) is probably the most used informant-based rating scale for the assessment of RRB and interests observed in ASD. The present study examined the psychometric properties of the Spanish version of the RBS-R in a sample of 233 participants with ASD, aged 3 to 63 years. Results revealed a six-factor model, good internal consistency, and concurrent-divergent validity. These findings suggest the utility of the Spanish version of RBS-R

AKP-11 - A Novel S1P1 Agonist with Favorable Safety Profile Attenuates Experimental Autoimmune Encephalomyelitis in Rat Model of Multiple Sclerosis

Sphingosine-1-phosphate receptor 1 (S1P1) mediated regulation of lymphocyte egress from lymphoid organs is recognized as the mechanism of FTY720 (Fingolimod, Gilenya) efficacy in relapsing-remitting forms of multiple sclerosis (RRMS). In this study we describe a novel S1P1 agonist AKP-11, next generation of S1P1 agonist, with immunomodulatory activities in cell culture model and for therapeutic efficacy against an animal model of MS, i.e. experimental autoimmune encephalomyelitis (EAE) but without the adverse effects observed with FTY720. Like FTY720, AKP-11 bound to S1P1 is internalized and activates intracellular AKT and ERKs cellular signaling pathways. In contrast to FTY720, AKP-11 mediated S1P1 downregulation is independent of sphingosine kinase activity indicating it to be a direct agonist of S1P1. The S1P1 loss and inhibition of lymphocyte egress by FTY720 leads to lymphopenia. In comparison with FTY720, oral administration of AKP-11 caused milder and reversible lymphopenia while providing a similar degree of therapeutic efficacy in the EAE animal model. Consistent with the observed reversible lymphopenia with AKP-11, the S1P1 recycled back to cell membrane in AKP-11 treated cells following its withdrawal, but not with withdrawal of FTY720. Accordingly, a smaller degree of ubiquitination and proteolysis of S1P1 was observed in AKP-11 treated cells as compared to FTY720. Consistent with previous observations, FTY720 treatment is associated with adverse effects of bradycardia and lung vascular leaks in rodents, whereas AKP-11 treatment had undetectable effects on bradycardia and reduced lung vascular leaks as compared to FTY720. Taken together, the data documents that AKP-11 treatment cause milder and reversible lymphopenia with milder adverse effects while maintaining therapeutic efficacy similar to that observed with FTY720, thus indicating therapeutic potential of AKP-11 for treatment of MS and related autoimmune disorders