; 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...

Plain English summary Whilst Patient and Public Involvement and Engagement (PPIE) are widely regarded as critical to developing clinical research, there is a perception that older adults may not be able to contribute and there is less emphasis on gaining a wide range of opinions before developing research questions or projects; for example an organisational change. This PPIE initiative used three PPIE processes including existing panels and wider networking to access older adults in the community who had used the hospital services and been discharged. Older adults expressed a range of views about their experience of discharge planning and this provided an important perspective on patients’ research priorities associated with their personal independence. Efforts were taken to ensure representative views across a cross section of the population. As a result of this initial PPIE, a permanent, co-ordinated ‘elders’ panel has been established to ensure a representation of older adult views for research, service development and evaluation. This panel has permanent, fully supported members who provide reflection and feedback on any projects and programmes relating to older people’s services in the City. Abstract Background Clinical academic research and service improvement is planned using Patient and Public Involvement and Engagement (PPIE) but older PPIE participants are consulted less often due to the perception that they are vulnerable or hard to engage. Objectives To consult frail older adults about a recently adopted service, discharge to assess (D2A), and to prioritise services improvements and research topics associated with the design and delivery of discharge from hospital. To use successive PPIE processes to enable a permanent PPIE panel to be established. Participants Following guidance from an established hospital PPI panel 27 older adult participants were recruited. Participants from Black, Asian and Minority Ethnic (BAME) communities, affluent and non-affluent areas and varied social circumstances were included. Methods Focus groups and individual interviews were conducted in participants own homes or nearby social venues. Results Priorities for discharge included remaining independent despite often feeling lonely at home; to remain in hospital if needed; and for services to ensure effective communication with families. The main research priority identified was facilitating independence, whilst establishing a permanent PPIE panel involving older adults was viewed favourably. Conclusions Taking a structured approach to PPIE enabled varied older peoples’ voices to express their priorities and concerns into early discharge from hospital, as well as enabling the development of health services research into hospital discharge planning and management. Older people as participants identified research...

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BackgroundDistress after prostate cancer treatment is a substantial burden for up to one-third of men diagnosed. Physical and emotional symptoms and health service use can intensify, yet men are reticent to accept support. To provide accessible support that can be cost effectively integrated into care pathways, we developed a unique, Web-based, self-guided, cognitive-behavior program incorporating filmed and interactive peer support.ObjectiveTo assess feasibility of the intervention among men experiencing distress after prostate cancer treatment. Demand, acceptability, change in distress and self-efficacy, and challenges for implementation in clinical practice were measured.MethodsA pre-post, within-participant comparison, mixed-methods research design was followed. Phase I and II were conducted in primary care psychological service and secondary care cancer service, respectively. Men received clinician-generated postal invitations: phase I, 432 men diagnosed <5 years; phase II, 606 men diagnosed <3.5 years. Consent was Web-based. Men with mild and moderate distress were enrolled. Web-based assessment included demographic, disease, treatment characteristics; distress (General Health Questionnaire-28); depression (Patient Health Questionnaire-9); anxiety (General Anxiety Disorder Scale-7); self-efficacy (Self-Efficacy for Symptom Control Inventory); satisfaction (author-generated, Likert-type questionnaire). Uptake and adherence were assessed with reference to the persuasive systems design model. Telephone interviews explored participant experience (phase II, n=10); interviews with health care professionals (n=3) explored implementation issues.ResultsA total of 135 men consented (phase I, 61/432, 14.1%; phase II, 74/606, 12.2%); from 96 eligible men screened for distress, 32% (30/96) entered the intervention (phase I, n=10; phase II, n=20). Twenty-four completed the Web-based program and assessments (phase I, n=8; phase II, n=16). Adherence for phase I and II was module completion rate 63% (mean 2.5, SD 1.9) versus 92% (mean 3.7, SD 1.0); rate of completing cognitive behavior therapy exercises 77% (mean 16.1, SD 6.2) versus 88% (mean 18.6, SD 3.9). Chat room activity occurred among 63% (5/8) and 75% (12/16) of men, respectively. In phase I, 75% (6/8) of men viewed all the films; in phase II, the total number of unique views weekly was 16, 11, 11, and 10, respectively. The phase II mood diary was completed by 100% (16/16) of men. Satisfaction was high for the program and films. Limited efficacy testing indicated improvement in distress baseline to post intervention: phase I, P=.03, r=−.55; phase II, P=.001, r=−.59. Self-efficacy improved for coping P=.02, r=−.41. Service assessment confirmed ease of assimilation into clinical practice and clarified health care practitioner roles.ConclusionsThe Web-based program is acceptable and innovative in clinical practice. It was endorsed by patients and has potential to positively impact the experience of men with distress after prostate cancer treatment. It can potentially b...