Clinical audit research and evaluation of motor neuron disease (CARE-MND): a national electronic platform for prospective, longitudinal monitoring of MND in Scotland.

Objectives: Launched in 1989, the Scottish Motor Neuron Disease Register (SMNDR) has provided a resource for prospective clinical data collection. However, in 2015 we aimed to evolve a system to allow: i) A patient-centered approach to care based on recognized standards, ii) Harmonized data sharing between Scottish health professionals in "real-time", iii) Regular audit of care to facilitate timely improvements in service delivery, and iv) Patient participation in a diverse range of observational and interventional research studies including clinical trials. Methods: We developed a standardized national electronic data platform-Clinical Audit Research and Evaluation of MND (CARE-MND) which integrates clinical audit and research data fields. Data completion pre- and post-CARE-MND were compared, guided by recently published National Institute for Clinical Excellence (NICE) recommendations. Statistical difference in data capture between time periods was assessed using Z-test of proportions. Results: Data field completion for the historical 2011-2014 period ranged from 4 to 95%; median 50%. CARE-MND capture ranged from 32 to 98%; median 87%. 15/17 fields were significantly more complete post-CARE-MND (p < 0.001). All MND nurse/allied health specialists in Scotland use the CARE-MND platform. Management of MND in Scotland is now coordinated through a standardized template. Conclusions: Through CARE-MND, national audits of MND care and interventions have been possible, leading to protocols for harmonized service provision. Stratification of the MND population is facilitating participation in observational and interventional studies. CARE-MND can act as a template for other neurological disorders.

Interleukin 12-augmented T cell proliferation of peripheral blood mononuclear cells from HIV-seropositive individuals is associated with interleukin 12 receptor beta 2 upregulation.

Interleukin 12 (IL-12) production is believed to be impaired in individuals with HIV infection and this impairment manifests early in disease, when the CD4(+) cell counts are within normal values. The reduced antigen-specific and mitogen-stimulated T cell-proliferative responses that occur in HIV infection can be corrected by the addition of recombinant human interleukin 12 (rhIL-12). As the IL-12 receptor (IL-12R) is central to the IL-12 signaling pathway, we examined whether the augmentation of antigen-specific proliferation of HIV(+) peripheral blood mononuclear cells (PBMCs) related to altered IL-12R expression. rhIL-12 augmented antigen-specific proliferation of HIV(+) PBMCs but not of HIV(-) PBMCs. Examination of resting PBMCs from HIV(+) and HIV(-) donors showed that neither of these populations expressed IL-12R beta 1 or IL-12R beta 2 chains on their cell surface as detected by flow cytometry. However, examination of mRNA showed that both IL-12R beta 1 and IL-12R beta 2 mRNAs were markedly reduced in HIV(+) PBMCs when compared with HIV(-) PBMCs. After mitogen activation there was an increase in IL-12R beta 1 expression on the cell surface of HIV(+) and HIV(-) PBMCs and this level was not altered by coculture with rhIL-12 or interferon gamma (IFN-gamma). However, coculture of phytohemagglutinin (PHA)-activated HIV(+) or HIV(-) PBMCs with rhIL-12 (but not IFN-gamma) increased IL-12R beta 2 expression on the cell surface of both populations. Examination at the message level showed a correction of IL-12R beta 1 to normal levels with activation that was further enhanced by rhIL-12 coculture for both the HIV(+) and HIV(-) PBMCs. However, although the level of IL-12R beta 2 for the HIV(+) PBMCs was normalized by PHA, rhIL-12 caused a further augmentation. This information provides a strong link between IL-12R upregulation, and the significant improvement in antigen-specific HIV-proliferative responses seen with the addition of rhIL-12. It also reveals that the dysfunction in IL-12R expression seen in cells from HIV(+) patients occurs at the transcriptional level. In addition, we provide further evidence that IL-12R beta 1 and IL-12R beta 2 regulation in human PBMCs is independent of IFN-gamma.