Awareness screening and referral patterns among pediatricians in the United States related to early clinical features of spinal muscular atrophy (SMA).

BACKGROUND: Spinal Muscular Atrophy (SMA), a leading genetic cause of death in infants, is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. While early diagnosis of SMA is critical to modifying disease progression and improving outcomes, serious diagnostic delays persist. There is a need to improve SMA awareness, screening, and referral patterns. METHODS: Two online surveys, developed by Cure SMA for general pediatricians, were distributed by Medscape Education via email (September 2018, n = 300, December 2019, n = 600). The surveys asked about adherence to the American Academy of Pediatrics (AAP) developmental screening and surveillance guidelines, comfort with identification of early signs of neuromuscular disease (NMD), familiarity with SMA, and barriers to timely referral. RESULTS: In 2018, 70.3% of survey respondents indicated comfort in identifying early signs of NMD and 67.3% noted familiarity with SMA. 52.7% correctly indicated the need for genetic testing to make a definitive diagnosis of SMA, 74.0% meet or exceed developmental screening recommendations, and 52.0% said they would immediately refer to a specialist. In 2019, with a larger sample, 73.0% adhere to developmental screening guidelines, and awareness of the genetic testing requirement for SMA was significantly lower by 7.7% (p < 0.03). Specialist wait times emerged as a barrier to referral, with 64.2% of respondents citing wait times of 1-6 months. CONCLUSIONS: Many pediatricians underutilize developmental screening tools and lack familiarity with diagnostic requirements for SMA. Continuing efforts to expand awareness and remove barriers to timely referral to SMA specialists, including reducing appointment wait times, are needed.

In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.

RATIONALE: One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes-a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ. OBJECTIVE: To develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle. METHODS AND RESULTS: We optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell-laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease. CONCLUSIONS: This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.

Medication Regimen Complexity in Patients Receiving Consultant Pharmacy Services in Home Health Care.

An interprofessional, team-based approach has become common in a variety of settings. However, consultant pharmacist participation in home health care (HHC) has been limited. To evaluate a potential need for pharmacists in HHC, the objective of this project was to document the medication complexity of patients seen by an established HHC consultant pharmacist service. This retrospective review reports on medication regimen complexity in 79 patients receiving this service using the Patient-Level Medication Regimen Complexity Index (MRCI) tool. The average MRCI score was 30 (± 15 standard deviation), suggesting a high level of medication regimen complexity in this population. High scores have been correlated with increased potential adverse drug events, 30-day hospital readmissions, and reduced adherence. Further research is needed for both the utilization of consultant pharmacists in HHC and the use of MRCI in identifying HHC patients needing pharmacist services.