Objective. We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized antiinterleukin-17 (anti-IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs).Methods. This randomized, double-blind, placebo- Results. Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821-combined groups (؊2.3, ؊2.4, and ؊2.3, respectively) than in the placebo group (؊1.7) at week 10 (P < 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events.Conclusion. LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA.

Objective. Tabalumab, a fully human IgG4 monoclonal antibody, neutralizes soluble and membranebound BAFF. The aim of this study was to examine the tolerability and efficacy of tabalumab in patients with active rheumatoid arthritis receiving methotrexate.Methods. In this randomized, double-blind, placebo-controlled, parallel, multiple-dose study, patients who were naive to biologic therapy received infusions of tabalumab (30, 60, or 160 mg) or placebo at weeks 0, 3, and 6 in combination with methotrexate and were evaluated for 24 weeks. The primary efficacy end point was the percentage of patients meeting American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16.Results. At week 16, the percentages of patients achieving an ACR20 response in the 30-mg (57.6%), 60-mg (67.6%), and 160-mg (51.5%) groups were significantly greater than the percentage of patients achieving an ACR20 response in the placebo group (29.4%; P < 0.05). There were initial transient increases from baseline in the frequency of CD20؉ and IgD؉/CD27؊ B cells, followed by reductions, although B cells were not completely depleted. Also, the frequency of IgD؊/CD27؉ B cells increased in all tabalumab groups compared with the placebo group and returned toward baseline levels by the end of the study. The incidence of adverse events was similar across all treatment groups; no deaths occurred. Serum IgM levels decreased significantly in all tabalumab groups combined compared with the placebo group. There were no significant decreases in serum IgG or IgA levels in the tabalumab groups compared with the placebo group.Conclusion. Tabalumab treatment significantly reduces the signs and symptoms of rheumatoid arthritis and has a safety profile similar to that seen with placebo treatment.

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Although the review found increased risk of open-angle glaucoma with pars plana vitrectomy, the studies were heterogenous or inconsistent regarding ocular hypertension and intraocular pressure increase. Larger studies should be conducted in homogenous cohorts of patients undergoing macular surgery, excluding complex conditions such as retinal detachment or diabetic retinopathy.

Purpose: To assess the impact of uncorrected hyperopia and hyperopic spectacle correction on children's academic performance. Design: Systematic review and meta-analysis Methods: We searched 9 electronic databases from inception to July 26, 2021, for studies assessing associations between hyperopia and academic performance. There were no restrictions on language, publication date, or geographic location. A quality checklist was applied. Random-effects models estimated pooled effect size as a standardized mean difference (SMD) in 4 outcome domains: cognitive skills, educational performance, reading skills, and reading speed. (PROSPERO registration: CRD-42021268972). Results: Twenty-five studies (21 observational and 4 interventional) out of 3415 met the inclusion criteria. No full-scale randomized trials were identified. Meta-analyses of the 5 studies revealed a small but significant adverse effect on educational performance in uncorrected hyperopic compared to emmetropic children {SMD À0.18 [95% confidence interval (CI), À0.27 to À0.09]; P < 0.001, 4 studies} and a moderate negative effect on reading skills in uncorrected hyperopic compared to emmetropic children [SMD À0.46 (95% CI, À0.90 to À0.03); P ¼ 0.036, 3 studies]. Reading skills were significantly worse in hyperopic than myopic children [SMD À0.29 (95% CI, À0.43 to À0.15); P < 0.001, 1 study]. Qualitative analysis on 10 (52.6%) of 19 studies excluded from metaanalysis found a significant (P < 0.05) association between uncorrected hyperopia and impaired academic performance. Two interventional studies found hyperopic spectacle correction significantly improved reading speed (P < 0.05). Conclusions: Evidence indicates that uncorrected hyperopia is associated with poor academic performance. Given the limitations of current methodologies, further research is needed to evaluate the impact on academic performance of providing hyperopic correction.