Introduction This paper describes the care coordination training program and results of an evaluation from its pilot in seven states. Despite the importance of practice-based care coordination, only 42.3% of children with special health care needs (CYSHCN) met all needed components of care coordination as defined by the Maternal Child Health Bureau. Recognizing that children with medically complex conditions often have lower rates of achieving care coordination within a medical home, the Region 4 Midwest Genetics Collaborative worked with families to develop a training to empower families in care coordination. The Care Coordination: Empowering Families(CCEF) training provides families with the knowledge, tools, and resources to engage with health, education and family support systems. This article gives an overview of the training and comprehensive evaluation. Methods Participants were family caregivers of children with genetic conditions and other special health care needs recruited in one of seven pilot states. Evaluation data were collected from 190 participants prior to and immediately following the training. An additional follow-up assessment one full year post training was completed by 80 participants (a response rate of 42%). Results Families who attended the training report being the primary source of care coordination for their children and 83.7% see their role in their child’s healthcare changing as a result of the training. The findings suggest that peer support and communication with providers increased as a result of the training over the course of the study. The data suggest that the training impacted how the family interacts with the child’s doctor, including initiating conversations to prepare their child for transition to adult health care. Further, families report system-level improvements 1 year later compared to the pre-training assessment. Discussion CCEF training is a promising practice for facilitating medical home use among CYSHCN.

Background Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. Methods CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Results Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. Conclusions This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.

BackgroundThe extent of cortical pathology is an important determinant of multiple sclerosis (MS) severity. Cortical demyelination and neurodegeneration are related to inflammation of the overlying leptomeninges, a more inflammatory CSF milieu and with parenchymal microglia and astroglia activation. These are all components of the compartmentalised inflammatory response. Compartmentalised inflammation is a feature of progressive MS, which is not targeted by disease modifying therapies. Complement is differentially expressed in the MS CSF and complement, and complement receptors, are associated with demyelination and neurodegeneration.MethodsTo better understand if complement activation in the leptomeninges is associated with underlying cortical demyelination, inflammation, and microglial activation, we performed a neuropathological study of progressive MS (n = 22, 14 females), neuroinflammatory (n = 8), and non-neurological disease controls (n = 10). We then quantified the relative extent of demyelination, connective tissue inflammation, complement, and complement receptor positive microglia/macrophages.ResultsComplement was elevated at the leptomeninges, subpial, and within and around vessels of the cortical grey matter. The extent of complement C1q immunoreactivity correlated with connective tissue infiltrates, whilst activation products C4d, Bb, and C3b associated with grey matter demyelination, and C3a receptor 1+ and C5a receptor 1+ microglia/macrophages closely apposed C3b labelled cells. The density of C3a receptor 1+ and C5a receptor 1+ cells was increased at the expanding edge of subpial and leukocortical lesions. C5a receptor 1+ cells expressed TNFα, iNOS and contained puncta immunoreactive for proteolipid protein, neurofilament and synaptophysin, suggesting their involvement in grey matter lesion expansion.InterpretationThe presence of products of complement activation at the brain surfaces, their association with the extent of underlying pathology and increased complement anaphylatoxin receptor positive microglia/macrophages at expanding cortical grey matter lesions, could represent a target to modify compartmentalised inflammation and cortical demyelination.

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