Absence of dystrophin makes skeletal muscle more susceptible to injury, resulting in breaches of the plasma membrane and chronic inflammation in Duchenne muscular dystrophy (DMD). Current management by glucocorticoids has unclear molecular benefits and harsh side effects. It is uncertain whether therapies that avoid hormonal stunting of growth and development, and/or immunosuppression, would be more or less beneficial. Here, we discover an oral drug with mechanisms that provide efficacy through anti-inflammatory signaling and membrane-stabilizing pathways, independent of hormonal or immunosuppressive effects. We find VBP15 protects and promotes efficient repair of skeletal muscle cells upon laser injury, in opposition to prednisolone. Potent inhibition of NF-κB is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. The translation of these drug mechanisms into DMD model mice improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens. These data demonstrate successful improvement of dystrophy independent of hormonal, growth, or immunosuppressive effects, indicating VBP15 merits clinical investigation for DMD and would benefit other chronic inflammatory diseases.
Coronavirus disease 2019 (COVID-19) is increasingly recognized as having significant long-term impact on physical and mental health. The Primary Care Wellbeing Service (PCWBS) in Bradford District Care NHS Foundation Trust (BDCFT) is a psychology-led specialist interdisciplinary team of health professionals specializing in persistent physical symptoms (PPS) and Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) with an emphasis on holistic integrated care. The PCWBS quickly recognized the risk of the long-term effects of COVID-19, particularly for social, health and care staff, and developed a 7-week virtual rehabilitation course which was piloted in October 2020. The “ Recovering from COVID” course takes a whole system, biopsychosocial approach to understanding COVID-19 and post-viral fatigue (PVF) and is delivered by an interdisciplinary team consisting of a clinical psychologist, physiotherapist, occupational therapist, dietitian, speech and language therapist, assistant psychologist, and a personal support navigator with support from a team administrator. The course focuses on understanding PVF, sleep optimization, nutrition, swallowing, activity management, energy conservation, stress management, breathing optimization, managing setbacks, and signposting to appropriate resources and services. Since the pilot, PCWBS has delivered 7 courses to support over 200 people suffering from post-COVID-19 syndrome. One hundred and forty-nine individuals that enrolled on the “ Recovering from COVID” course completed the EQ-5D-5L to assess Health-related quality of life (HRQoL) across 5 dimensions, including problems with mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Subsequently, 76 individuals completed these measures at the end of the rehabilitation course showing that patient ratings were significantly improved. In response to the NIHR recommendation for rapid evaluation of different service models for supporting people with post-COVID-19 syndrome, this data offers hope that rehabilitation is effective in reversing some of the problems faced by people living with the long-term effects of COVID-19.
ObjectiveAdvance care planning (ACP) is a core quality measure in caring for individuals with Parkinson disease (PD) and there are no best practice standards for how to incorporate ACP into PD care. This study describes patient and care partner perspectives on ACP to inform a patient- and care partner-centered framework for clinical care.MethodsThis is a qualitative descriptive study of 30 patients with PD and 30 care partners within a multisite, randomized clinical trial of neuropalliative care compared to standard care. Participants were individually interviewed about perspectives on ACP, including prior and current experiences, barriers to ACP, and suggestions for integration into care. Interviews were analyzed using theme analysis to identify key themes.ResultsFour themes illustrate how patients and care partners perceive ACP as part of clinical care: (1) personal definitions of ACP vary in the context of PD; (2) patient, relationship, and health care system barriers exist to engaging in ACP; (3) care partners play an active role in ACP; (4) a palliative care approach positively influences ACP. Taken together, the themes support clinician initiation of ACP discussions and interdisciplinary approaches to help patients and care partners overcome barriers to ACP.ConclusionsACP in PD may be influenced by patient and care partner perceptions and misperceptions, symptoms of PD (e.g., apathy, cognitive dysfunction, disease severity), and models of clinical care. Optimal engagement of patients with PD and care partners in ACP should proactively address misperceptions of ACP and utilize clinic teams and workflow routines to incorporate ACP into regular care.
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