; 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...

Objective: Telemental health (TMH) is not well described for mental health service delivery during crises. Most child and adolescent psychiatry training programs have not integrated TMH into their curricula and are ill equipped to respond during crises to their patients' needs. In this study, we present the implementation of a home-based TMH (HB-TMH) service during the COVID-19 pandemic. Methods: We describe the technological, administrative, training, and clinical implementation components involved in transitioning a comprehensive outpatient child and adolescent psychiatry program to a HB-TMH virtual clinic. Results: The transition was accomplished in 6 weeks. Most in-clinic services were rapidly moved off campus to the home. Owing to challenges encountered with each implementation component, phone sessions bridged the transition from in-clinic to reliable virtual appointments. Within 3 weeks (March 20, 2020) of planning for HB-TMH, 67% of all appointments were conducted at home, and within 4 weeks (March 27, 2020), 90% were conducted at home. By week 6 (April 3, 2020), reliable HB-TMH appointments were implemented. Conclusions: The COVID-19 pandemic crisis created the opportunity to innovate a solution to disrupted care for our established patients and to create a resource for youth who developed problems during the crisis. Our department was experienced in providing TMH services that facilitated the transition to HB-TMH, yet still had to overcome known and unanticipated challenges. Our experience provides a roadmap for establishing a HB-TMH service with focus on rapid implementation. It also demonstrates a role for TMH during (rather than after) future crises when usual community resources are not available.

No abstract

OBJECTIVE Peripherally inserted central catheter (PICC) tip malposition is potentially associated with complications, and postplacement adjustment of PICCs is widely performed. We sought to characterize the association between central line–associated bloodstream infection (CLABSI) or venous thrombus (VT) and PICC adjustment. DESIGN Retrospective cohort study. SETTING University of Michigan Health System, a large referral hospital. PATIENTS Patients who had PICCs placed between February 2007 and August 2007. METHODS The primary outcomes were development of CLABSI within 14 days or VT within 60 days of postplacement PICC adjustment, identified by review of patient electronic medical records. RESULTS There were 57 CLABSIs (2.69/1,000 PICC-days) and 47 VTs (1.23/1,000 PICC-days); 609 individuals had 1, 134 had 2, and 33 had 3 or more adjustments. One adjustment was protective against CLABSI (P = .04), whereas 2 or 3 or more adjustments had no association with CLABSI (P = .58 and .47, respectively). One, 2, and 3 or more adjustments had no association with VT formation (P = .59, .85, and .78, respectively). Immunosuppression (P < .01), power-injectable PICCs (P = .05), and 3 PICC lumens compared with 1 lumen (P = .02) were associated with CLABSI. Power-injectable PICCs were also associated with increased VT formation (P = .03). CONCLUSIONS Immunosuppression and 3 PICC lumens were associated with increased risk of CLABSI. Power-injectable PICCs were associated with increased risk of CLABSI and VT formation. Postplacement adjustment of PICCs was not associated with increased risk of CLABSI or VT.