A Residency Program Curriculum to Improve Health Care Transitions for Autistic Individuals.

OBJECTIVES: Physical and mental health outcomes of autistic individuals deteriorate during transition to adulthood. The study aims to identify opportunities to improve physician knowledge in health-care transitions (HCT) for autistic individuals by understanding perceived versus experienced facilitators and barriers in overall HCT curriculum implementation in graduate medical education. METHODS: Medicine-Pediatrics program directors participated in a Health Care Transition Residency Curriculum Collaborative Improvement Network and used an iterative process to develop and improve HCT curricula. Pre- and postcollaborative semistructured interviews were administered to program directors. The study occurred over 9 months (July 2018-February 2019). Recurring interview themes were analyzed utilizing Dedoose qualitative coding software and presented utilizing percentages and proportions. RESULTS: Most program directors developed curricula in response to a gap in their current transition curricula. All program directors partially or completely met their goals during the collaborative. The most common types of curricular delivery were didactic (65%) and clinical experience-based (53%). Some tested unique delivery platforms, like the electronic medical record system (29%) and online modules (24%). Program directors often involved residents in the curricular development process and overwhelmingly (65%) felt this was a major facilitator. Competing priorities of faculty (71%) and of residents (53%) were the most common barriers. CONCLUSIONS: Gaps in HCT curricula delivery were primarily attributed to suboptimal health care systems where training occurs, though existing clinical experiences and diverse learning modalities were successfully leveraged. Using a quality improvement framework and actively engaging resident trainees in curriculum development were successful strategies programs used in the development of HCT curricula.

The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning.

In the present NONA immune longitudinal study, we further examine the previously identified T cell immune risk phenotype (IRP), relative inflammatory activity, morbidity and 2-year mortality in very old individuals >90 years. T-cell subsets as well as the inflammatory markers IL-6, IL-10, C-reactive protein, transthyretin and albumin were evaluated. IRP and low-grade inflammation predicted 57% of observed deaths and 97% of survival over 2 years, and was not significantly affected by individuals' health status, suggesting that the physiological ageing processes of T-cell immunosenescence and low-grade inflammation are of primary importance in late life survival. IRP non-survivors showed only a minor inflammatory activity at baseline, but had in contrast to survivors developed increased activity at follow-up. The results suggest a sequence of stages for IRP individuals that begin with acquisition of CMV infection in earlier life, followed by generation of CD8+CD28- cells to control persistent CMV infection and eventually the development of an IRP. Intriguingly, we also found that rare individuals moved out of the IRP category by a process of immune suppression, including increases in IL-6 and IL-10 and decreases in the number of CD3+CD8+CD28- cells. The further characterisation of these exceptional individuals may allow insight into remedial approaches for those who remain in the IRP category until death.

An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans.

In the previous OCTO longitudinal study, we identified an immune risk phenotype (IRP) of high CD8 and low CD4 numbers and poor proliferative response. We also demonstrated that cognitive impairment constitutes a major predictor of nonsurvival. In the present NONA longitudinal study, we simultaneously examine in a model of allostatic load IRP and compromised cognition in 4-year survival in a population-based sample (n = 138, 86-94 years). Immune system measurements consisted of determinations of T-cell subsets, plasma interleukin 6 and cytomegalovirus and Epstein-Barr virus serology. Interleukin 2 responsiveness to concanavalin A, using data from the previous OCTO (octogenarians) immune study, hereafter OCTO immune, was also examined. Cognitive status was rated using a battery of neuropsychological tests. Logistic regression indicated that the IRP and cognitive impairment together predicted 58% of observed deaths. IRP was associated with late differentiated CD8+CD28-CD27- cells (p < .001), decreased interleukin 2 responsiveness (p < .05) and persistent viral infection (p < .01). Cognitive impairment was associated with increased plasma interleukin 6 (p < .001). IRP individuals with cognitive impairment were all deceased at the follow-up, indicating an allostatic overload.

Morbidity does not influence the T-cell immune risk phenotype in the elderly: findings in the Swedish NONA Immune Study using sample selection protocols.

A critical issue in our understanding of ageing and the immune system refers to the health status of the population from which inferences are drawn. The commonly used SENIEUR protocol, selecting individuals representing 'normal ageing' has recently been under debate because a substantial amount of individuals with various health problems are excluded. The aim of the present study was to investigate the influence of morbidity on immune parameters and to evaluate the associations with the T-cell immune risk phenotype (IRP), related to cytomegalovirus (CMV) seropositivity by applying the SENIEUR protocol and the OCTO-Immune protocol in the unselected population based sample (n=138) of oldest-olds, participating in the Swedish NONA Immune Study. The SENIEUR protocol excluded over 90% of the sample whereas the OCTO-Immune protocol excluded almost 65% of the sample. Three independent groups, very healthy (SENIEUR), moderately healthy (OCTO-Immune) and frail (non-SENIEUR/non-OCTO-Immune) were created. Flow cytometry studies on lymphocyte sub-populations revealed no significant difference in CD4/CD8 ratio, CD3+CD4-CD8+, CD3+CD4+CD8-, CD8+CD57+CD28-, CD8+CD56+CD57- or CD8+CD56+CD57+ between the very healthy, moderately healthy and the frail subsamples. Our findings indicate that morbidity does not significantly influence the T-cell immune risk profile in the elderly, and we suggest the inclusion of broader samples in future immunogerontological studies.

Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study.

Results from a previous longitudinal study, the Swedish OCTO-Immune study, indicated that the combination of higher CD8 peripheral blood lymphocytes (PBLs), decreased CD4 PBLs, and poor proliferative response to mitogenic stimulation in very old humans were associated with an increased 2 year mortality. In follow up studies this combination of immune parameters was significantly associated with a CD4/CD8 ratio less than one and positive IgG serologic titers to cytomegalovirus (CMV). The present study, the Swedish NONA-Immune study, was an extension of that study, using a new sample of the very old. The results of this study confirmed the results of the previous study and extended the surface marker profile of the PBLs, indicating that the CD4/CD8 ratio change is associated with increased CD8 cells, decreased CD4 cells, and lymphocyte activation. The predominant phenotypes of the CD3+CD8+ cells were CD27-, CD28-, CD56+, and CD57+, CD45RA+, and double marked CD45RA+RO+. As in the OCTO study, the NONA-Immune data indicated that the changes are associated significantly with seropositive responses to CMV.