; and the Zilucoplan MG Study Group IMPORTANCE Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life. OBJECTIVE To evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled phase 2 clinical trial at 25 study sites across North America recruited participants between December 2017 and August 2018. Fifty-seven patients were screened, of whom 12 did not meet inclusion criteria and 1 was lost to follow-up after randomization but before receiving study drug, resulting in a total of 44 acetylcholine receptor autoantibody (AChR-Ab)-positive patients with gMG with baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12, regardless of treatment history. INTERVENTIONS Patients were randomized 1:1:1 to a daily SC self-injection of placebo, 0.1-mg/kg zilucoplan, or 0.3-mg/kg zilucoplan for 12 weeks. MAIN OUTCOMES AND MEASURES The primary and key secondary end points were the change from baseline to week 12 in QMG and MG Activities of Daily Living scores, respectively. Significance testing was prespecified at a 1-sided α of .10. Safety and tolerability were also assessed. RESULTS The study of 44 patients was well balanced across the 3 treatment arms with respect to key demographic and disease-specific variables. The mean age of patients across all 3 treatment groups ranged from 45.5 to 54.6 years and most patients were white (average proportions across 3 treatment groups: 78.6%-86.7%). Clinically meaningful and statistically significant improvements in primary and key secondary efficacy end points were observed. Zilucoplan at a dose of 0.3 mg/kg SC daily resulted in a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change,-2.8; P = .05) and 3.4 points in the MG Activities of Daily Living score (placebo-corrected change,-2.3; P = .04). Clinically meaningful and statistically significant improvements were also observed in other secondary end points, the MG Composite and MG Quality-of-Life scores. Outcomes for the 0.1-mg/kg SC daily dose were also statistically significant but slower in onset and less pronounced than with the 0.3-mg/kg dose. Rescue therapy (intravenous immunoglobulin or plasma exchange) was required in 3 of 15, 1 of 15, and 0 of 14 participants in the placebo, 0.1-mg/kg zilucoplan, and 0.3-mg/kg zilucoplan arms, respectively. Zilucoplan was observed to have a favorable safety and tolerability profile. CONCLUSIONS AND RELEVANCE Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab...

Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR). Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR. Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles.

Background: Erythropoiesis-stimulating agent (ESA) resistance remains incompletely understood among hemodialysis (HD) patients. Method: A retrospective, multicenter study was designed to analyze data from 1,934 patients followed for up to two years. The outcome measure was the erythropoietin resistance index (ERI), defined as erythropoietin dosage over a week divided by the post-HD weight and hemoglobin value. Results: Multivariate analysis revealed albumin, Kt/V, transferrin saturation, statin use and male gender to be inversely related to ERI, whereas parathyroid hormone and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) use were associated with higher ESA resistance. ERI was statistically lower in patients with higher levels of albumin (p < 0.001) and with higher transferrin saturation levels (p < 0.05). Discussion: The results allow for a better understanding of predictors of erythropoietin resistance among HD patients including not extensively studied factors such as statin and ACEI/ARB use.

Background Factors at multiple ecological levels, including the child, family, home, medical care, and community, impact adolescent asthma outcomes. Objective This systematic review characterizes behavioral interventions at the child, family, home, medical system, and community level to improve asthma management among adolescents. Methods A systematic search of PubMed, SCOPUS, OVID, PsycINFO, CINAHL, and reference review databases was conducted from January 1, 2000 through August 10, 2014. Articles were included if the title or abstract included asthma AND intervention AND (Education OR self-management OR behavioral OR technology OR trigger reduction); and the mean/median age of participants was between eleven and sixteen years. We compared populations, intervention characteristics, study designs, outcomes, settings, and intervention levels across studies to evaluate behavioral interventions to improve asthma management for adolescents. Results Of 1230 articles identified and reviewed, 24 articles (21 unique studies) met inclusion criteria. Promising approaches to improving adherence to daily controller medications include: objective monitoring of inhaled corticosteroid adherence with allergist/immunologist feedback on medication taking behavior and school nurse directly observed therapy. Efficacy at increasing asthma self-management skills was demonstrated using group interactive learning in the school setting. This systematic review is not a meta-analysis, thus limiting its quantitative assessment of studies. Publication bias may also limit our findings. Conclusions Novel strategies to objectively increase controller medication adherence for adolescents include allergist/immunologist feedback and school nurse directly observed therapy. Schools, the most common setting across studies in this review, provide the opportunity for group interactive learning to improve asthma knowledge and self-management skills.

The World Bank withholds loan disbursements in order to build a reputation for enforcing conditionality, and multinational firms lobby for these funds to be released. Using data drawn from World Bank reports, we find evidence that (1) participation by Fortune 500 multinational corporations as project contractors and (2) investments by these firms are associated with disbursements that are unjustified by project performance. In addition, these measures of corporate interest are associated with inflated project evaluations. These effects are limited to multinational corporations headquartered in the United States or Japan, suggesting that the influence of private actors depends on access to particular national policy networks. In contrast to the evidence of corporate influence, we find no consistent evidence of geopolitical influences.