Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is an autoimmune disease with a heterogenous clinical presentation and unpredictable response to available therapies. This personalized transcriptomics study sought proof-of-concept for single-cell RNA sequencing to characterize patient-specific immune profiles. METHODS: Whole blood samples from six untreated children, newly diagnosed with JIA, and two healthy controls were cultured for 24 h with or without ex vivo TNF stimulation and subjected to scRNAseq to examine cellular populations and transcript expression in PBMCs. A novel analytical pipeline, scPool, was developed wherein cells are first pooled into pseudocells prior to expression analysis, facilitating variance partitioning of the effects of TNF stimulus, JIA disease status, and individual donor. RESULTS: Seventeen robust immune cell-types were identified, the abundance of which was significantly affected by TNF stimulus, which resulted in notable elevation of memory CD8 + T-cells and NK56 cells, but down-regulation of naïve B-cell proportions. Memory CD8 + and CD4 + T-cells were also both reduced in the JIA cases relative to two controls. Significant differential expression responses to TNF stimulus were also characterized, with monocytes showing more transcriptional shifts than T-lymphocyte subsets, while the B-cell response was more limited. We also show that donor variability exceeds the small degree of possible intrinsic differentiation between JIA and control profiles. An incidental finding of interest was association of HLA-DQA2 and HLA-DRB5 expression with JIA status. CONCLUSIONS: These results support the development of personalized immune-profiling combined with ex-vivo immune stimulation for evaluation of patient-specific modes of immune cell activity in autoimmune rheumatic disease.

Older adult falls prevention behaviors 60 days post-discharge from an urban emergency department after treatment for a fall.

BACKGROUND: Falls are a common and debilitating health problem for older adults. Older adults are often treated and discharged home by emergency department (ED)-based providers with the hope they will receive falls prevention resources and referrals from their primary care provider. This descriptive study investigated falls prevention activities, including interactions with primary care providers, among community-dwelling older adults who were discharged home after presenting to an ED with a fall-related injury. METHODS: We enrolled English speaking patients, aged ≥ 65 years, who presented to the ED of an urban level one trauma center with a fall or fall related injury and discharged home. During subjects' initial visits to the ED, we screened and enrolled patients, gathered patient demographics and provided them with a flyer for a Matter of Balance course. Sixty-days post enrollment, we conducted a phone follow-up interview to collect information on post-fall behaviors including information regarding the efforts to engage family and the primary care provider, enroll in a falls prevention program, assess patients' attitudes towards falling and experiences with any subsequent falls. RESULTS: Eighty-seven community-dwelling people between the ages of 65 and 90 were recruited, the majority (76%) being women. Seventy-one percent of subjects reported talking to their provider regarding the fall; 37% reported engaging in falls prevention activities. No subjects reported enrolling in a fall prevention program although two reported contacting falls program staff. Fourteen percent of subjects (n=12) reported a recurrent fall and 8% (7) reported returning to the ED after a recurrent fall. CONCLUSIONS: Findings indicate a low rate of initiating fall prevention behaviors following an ED visit for a fall-related injury among community-dwelling older adults, and highlight the ED visit as an important, but underutilized, opportunity to mobilize health care resources for people at high risk for subsequent falls.

A statewide baseline inventory of evidence-based fall prevention programs for older adults.

BACKGROUND: The Massachusetts (MA) Department of Public Health engaged the Injury Prevention Center at Boston Medical Center to develop a statewide baseline (2012) inventory of evidence-based (EB) community falls prevention programs for community-dwelling older adults. METHODS: A web-based survey of organizations (n = 825) serving older adults was deployed in two parts. The Directors' survey determined if a falls prevention program had been offered in 2012, the salience (rating of importance) of falls prevention for the organization, and intention to offer future falls prevention programming. A falls prevention program offered in 2012 triggered a second survey of Director-designated Coordinators to obtain information on programs' dates and locations. For the last program offered, data were collected on the number of participants, the training and occupations of program facilitators, and program funding. The last programs served as a cross-sectional sample of all programs offered during 2012. RESULTS: Response rates were 55 % (N = 457) and 86 % (N = 112) for the Directors' and Coordinators' surveys, respectively. The mean salience score for falls prevention was 3.68, on a 1-5 (most salient) scale; 12 % of respondents indicated offering ≥1 evidence-based program during 2012. We documented 107 EB programs, the majority of which (83 %) were offered by public agencies that serve older adults. CONCLUSIONS: Infrastructure for deployment of EB falls prevention programs is developing in MA, despite the absence of institutionalized funding, legislative mandates, widespread referrals from healthcare providers, or health insurance reimbursement.

Using surveillance data to inform a SUID reduction strategy in Massachusetts.

BACKGROUND: Non-supine infant sleep positions put infants at risk for sudden unexpected infant death (SUID). Disparities in safe sleep practices are associated with maternal income and race/ethnicity. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) is a nutrition supplement program for low-income (≤185% Federal Poverty Level) pregnant and postpartum women. Currently in Massachusetts, approximately 40% of pregnant/postpartum women are WIC clients. To inform the development of a SUID intervention strategy, the Massachusetts Department of Public Health (MDPH) investigated the association between WIC status and infant safe sleep practices among postpartum Massachusetts mothers using data from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. METHODS: PRAMS is an ongoing statewide health surveillance system of new mothers conducted by the MDPH in collaboration with the Centers for Disease Control and Prevention (CDC). PRAMS includes questions about infant sleep position and mothers' prenatal WIC status. Risk Ratio (RR) and 95 percent confidence intervals (CI) were calculated for infant supine sleep positioning by WIC enrollment, yearly and in aggregate (2007-2010). RESULTS/OUTCOMES: The aggregate (2007-2010) weighted sample included 276,252 women (weighted n ≈ 69,063 women/year; mean survey response rate 69%). Compared to non-WIC mothers, WIC mothers were less likely to usually or always place their infants in supine sleeping positions [RR = 0.81 (95% CI: 0.80, 0.81)]. Overall, significant differences were found for each year (2007, 2008, 2009, 2010), and in aggregate (2007-2010) by WIC status. CONCLUSION: Massachusetts WIC mothers more frequently placed their babies in non-supine positions than non-WIC mothers. While this relationship likely reflects the demographic factors associated with safe sleep practices (e.g., maternal income and race/ethnicity), the finding informed the deployment of an intervention strategy for SUID prevention. Given WIC's statewide infrastructure and the large proportion of pregnant/postpartum women in Massachusetts that are enrolled in WIC, a WIC-based safe sleep intervention may be an effective SUID reduction strategy with potential national application.