ABSTRACT
Background & Aim: Umbilical cord blood (CB) and mesenchymal stromal cells (MSC) have shown safety in children with cerebral palsy (CP). While early phase clinical trials suggest potential functional benefit, small sample sizes, heterogeneous populations, and variable cell doses have impaired accurate assessment of motor gains following treatment. Aim: Describe change in gross motor function in young children with CP after treatment with high-dose allogeneic unrelated donor CB or allogeneic, third party human cord tissue-derived MSC (hCT-MSC) 12 months post treatment. Methods, Results & Conclusion: We conducted a phase 2 randomized trial of 90 children ages 2-4 years with hypertonic CP due to hypoxic ischemic encephalopathy, periventricular leukomalacia, or in utero stroke/bleed. Randomization, stratified by etiology and severity (Gross Motor Function Classification System (GMFCS) level), was to: (a) 10×107 total nucleated cells (TNC)/kg allogeneic CB at baseline, (b) three doses of 2×106 cells/kg hCT-MSC given at baseline, 3, and 6 months, or (c) Natural History in which 10×107 TNC/kg allogeneic CB was given at one year. Infusions were intravenous and premedicated with diphenhydramine and methylprednisolone without immunosuppression. Primary outcome was change in motor function one-year post enrollment, measured by the Gross Motor Function Measure-66 (GMFM-66). Ninety children (median 3.5 years) were randomized and completed baseline and 6-month evaluations. Due to the COVID pandemic, only 68 completed 12-month assessments. The only adverse events (AEs) related to the cell products were 8 transient infusion reactions (3 CB, 5 hCT-MSC). An additional 95 non-severe AEs and 33 severe AEs were unrelated to the products. At 6 months, there was no statistical difference in change in GMFM-66 scores between Natural History (n=31) and either treatment group (CB n=31, hCTMSC n=28). At 12 months, after adjustment for baseline GMFCS level, GMFM-66 score, and etiology of CP, the mean GMFM-66 score of the hCT- MSC group (n=23) was 1.4 points higher than Natural History (n=25;95% CI: -1.1, 4.0;p=0.27) and the CB group (n=20) was 3.3 points higher than Natural History (95% CI: 0.59, 5.93;p=0.02). High dose allogeneic CB, but not hCT-MSC, infusion is associated with gross motor improvement in young children with CP, consistent with the dose effect in a prior study of autologous CB. A phase 3 randomized placebo-controlled study should be performed to confirm the CB observation.
ABSTRACT
Introduction: COVID-19 has brought to the fore an urgent need for secure information and communication technology (ICT) supported healthcare delivery, as the pertinence of infection control and social distancing continues. Telehealth for pediatric care incorporates additional layers of complexity compared with adult services for a variety of reasons including logistical, privacy, parental consent, child assent, child welfare, and quality concerns. There is no systematic evidence synthesis available that outlines the implementation issues for incorporating telehealth to pediatric services generally, or how users perceive these issues. Methods: We conducted a rapid mixed-methods evidence synthesis to identify barriers, facilitators, and documented stakeholder experiences of implementing pediatric telehealth, to inform the pandemic response. A systematic search was undertaken by a research librarian in MEDLINE for relevant studies. All identified records were blind double-screened by two reviewers. Implementation-related data were extracted, and studies quality appraised using the Mixed-Methods Appraisal Tool. Qualitative findings were analyzed thematically and then mapped to the Consolidated Framework for Implementation Research. Quantitative findings about barriers and facilitators for implementation were narratively synthesized. Results: We identified 27 eligible studies (19 quantitative;5 mixed-methods, 3 qualitative). Important challenges highlighted from the perspective of the healthcare providers included issues with ICT proficiency, lack of confidence in the quality/reliability of the technology, connectivity issues, concerns around legal issues, increased administrative burden and/ or fear of inability to conduct thorough examinations with reliance on subjective descriptions. Facilitators included clear dissemination of the aims of ICT services, involvement of staff throughout planning and implementation, sufficient training, and cultivation of telehealth champions. Families often expressed preference for in-person visits but those who had tried tele-consultations, lived far from clinics, or perceived increased convenience with technology considered telemedicine more favorably. Concerns from parents included the responsibility of describing their child's condition in the absence of an examination. Conclusion: Healthcare providers and families who have experienced tele-consultations generally report high satisfaction and usability for such services. The use of ICT to facilitate pediatric healthcare consultations is feasible for certain clinical encounters and can work well with appropriate planning and quality facilities in place.