Reference/Citation: Collins N, Bisset L, McPoil T, Vicenzino B. authors, and author affiliations of included RCTs were masked from 2 of the reviewers who independently assessed the included RCTs for methodologic quality using a altered PEDro level plus 3 additional items (justification of sample size, use of end result steps with known validity and reliability, and reporting of adverse or side effects). Disagreements on methodologic quality were resolved with consensus or by a third reviewer. The effect sizes for CD74 the included 803712-79-0 manufacture RCTs were represented by relative risk (RR) for dichotomous outcomes and standardized mean difference (SMD) for continuous data. Confidence intervals (CIs) were reported for RR and SMD. Study data were extracted directly from each of the included studies. If provided, data from intention-to-treat analysis were extracted. Study authors were contacted when insufficient data were reported. A meta-analysis (random-effects model) was conducted using Review Manager (version 4.2; The Nordic Cochrane Centre, Copenhagen, Denmark). Main Results: The search recognized 3192 potentially relevant studies. Full articles were retrieved for 327 studies. Twenty-two of the 327 studies met the inclusion criteria. Because the authors of 1 1 study used the same methods to statement on 2 populations, a total of 23 RCTs were included in the systematic review. Prevention of lower limb overuse conditions with the use of foot orthoses was reported in 8 RCTs (7 studies). The effect of foot orthoses in the treatment of lower 803712-79-0 manufacture limb overuse conditions was reported in 15 RCTs. Of the 23 RCTs, the cost-effectiveness of foot orthoses was reported in 2 and the adverse effects of foot orthoses were reported in 8. Across the prevention RCTs, data were available for analysis for 803712-79-0 manufacture a range of 47 to 417 participants with 8 to 16?weeks of follow-up. Based on 4 RCTs in which the experts examined prevention of lower limb overuse conditions with foot orthoses versus control in military staff, the RR was 1.49 (95% CI ?=? 1.07, 2.08). A clinically beneficial effect size was set a priori at 1.5 or greater for the foot-orthoses group or at 0.7 or less for the comparison group. Based on 2 RCTs reported in 1 study of the use of custom versus prefabricated foot orthoses for prevention of lower limb overuse conditions, no significant difference in risk was found (RR ?=? 1.14, 95% CI ?=? 0.90, 1.44). In their calculating and reporting of RR, the authors do not appear to have followed convention. Across the treatment RCTs, data were available for analysis for a range of 18 to 133 participants with 8 to 52?weeks of follow-up. The authors of the treatment RCTs reported a variety of outcome steps. Two of these, patient-perceived treatment effect (PPE) and pain on the visual analog level (VAS), were used to calculate an overall treatment effect 803712-79-0 manufacture (PPE as RR and VAS as SMD). Based on 2 RCTs examining foot orthoses versus control, no significant difference in PPE was found (RR ?=? 1.01, 95% CI ?=? 0.61, 1.68). Based on 2 RCTs in which 803712-79-0 manufacture custom versus prefabricated foot orthoses were examined, no significant difference in PPE was found (RR ?=? 0.88, 95% CI ?=? 0.42, 1.81). The VAS data reported in the text appear to contradict the VAS.