Closing the Gap: A Comparison of Engagement Interventions to Achieve Equitable Breast Cancer Screening in Rural Illinois.

Mammography screening rates are typically lower in those with less economic advantage (EA). This study, conducted at an integrated health care system covering a mixed rurality population, assessed the ability of interventions (text messages linking to a Web microsite, digital health care workers, and a community health fair) to affect mammography screening rates and disparity in those rates among different EA populations. Payor type served as a proxy for greater (commercially insured) versus lower (Medicaid insured) EA. 4,342 subjects were included across the preintervention ("Pre") and postintervention ("Post") periods. Interventions were prospectively applied to all Medicaid subjects and randomly selected commercial subjects. Applying interventions only to lower EA subjects reversed the screening rate disparity (2.6% Pre vs. -3.7% Post, odds ratio [OR] 2.4 P < 0.01). When intervention arms ("Least," "More," "Most") were equally applied, screening rates in both EA groups significantly increased in the More arm (Medicaid OR = 2.04 P = 0.04, Commercial OR = 3.08 P < 0.01) and Most arm (Medicaid OR 2.57 P < 0.01, Commercial OR 2.33 P < 0.01), but not in the Least (text-only) arm (Medicaid OR 1.83 P = 0.11, Commercial OR 1.72 P = 0.09), although this text-only arm was inadequately powered to detect a difference. In summary, targeting interventions to those with lower EA reversed screening rate disparities, text messaging combined with other interventions improved screening rates in both groups, and future research is needed to determine whether interventions can simultaneously improve screening rates for all without worsening the disparity.

Risk Factors for Longer Pediatric Intensive Care Unit Length of Stay Among Children Who Required Escalation of Care Within 24 Hours of Admission.

OBJECTIVE: Children who require early escalation of care (EOC) to the pediatric intensive care unit (PICU) after floor admission have higher mortality and increased hospital length of stay (LOS) as compared with direct emergency department (ED) admissions. This study was designed to identify subgroups of patients within this cohort (EOC to PICU within 24 hours of hospital admission) who have worse outcomes (actual PICU LOS [aLOS] > predicted PICU LOS [pLOS]). METHODS: This was a retrospective single-center cohort study. Patients who required EOC to PICU from January 2015 to December 2019 within 24 hours of admission were included. Postoperative patients, missing cause of EOC, and mortality were excluded. Predicted LOS was calculated based on Pediatric Risk of Mortality scores. Patients with aLOS > pLOS (group A) were compared with patients with aLOS ≤ pLOS (group B). Multivariable logistic regression was performed to adjust for confounders. RESULTS: Of 587 patients transferred to PICU after hospital admission during the study period, 286 patients met the study criteria (group A, n = 69; group B, n = 217). The 2 groups were similar in age, race, the severity of illness, and ED vitals and therapies. A higher proportion of patients in group B had EOC ≤ 6 hours of admission (51.1% vs 36.2%, P = 0.03), and a higher proportion in group A required Mechanical ventilation (56% vs 34%, P = 0.01). On multivariable regression, patients who required EOC to PICU after 6 hours after admission (adjusted odds ratio, 2.27; 95% confidence interval [CI] 1.2, 4.0), p,<0.01) and patients admitted to the floor from referral hospitals (adjusted odds ratio, 1.8; 95% confidence interval, 1.0-3.2), P = 0.04) had higher risk of greater than PLOS. CONCLUSIONS: Among patients who required EOC to PICU, risk factors associated with aLOS > pLOS were patients who required EOC to PICU longer than 6 hours after admission to the hospital and patients admitted to the floor as a transfer from referral hospitals.

ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder.

Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACCELERATE natural history registry. ACCELERATE includes a traditional physician-reported arm and a patient-powered arm, which enables patients to directly contribute medical data and biospecimens. This study design enables successful enrollment, with the 5-year minimum enrollment goal being met in 2 years. A median of 683 clinical, laboratory, and imaging data elements are captured per patient in the patient-powered arm compared with 37 in the physician-reported arm. These data reveal subgrouping characteristics, identify off-label treatments, support treatment guidelines, and are used in 17 clinical and translational studies. This feasibility study demonstrates that the direct-to-patient design is effective for collecting natural history data and biospecimens, tracking therapies, and providing critical research infrastructure.

Increased mTOR activation in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly understood hematologic disorder characterized by lymphadenopathy, systemic inflammation, cytopenias, and life-threatening multiorgan dysfunction. Interleukin-6 (IL-6) inhibition effectively treats approximately one-third of patients. Limited options exist for nonresponders, because the etiology, dysregulated cell types, and signaling pathways are unknown. We previously reported 3 anti-IL-6 nonresponders with increased mTOR activation who responded to mTOR inhibition with sirolimus. We investigated mTOR signaling in tissue and serum proteomes from iMCD patients and controls. mTOR activation was increased in the interfollicular space of iMCD lymph nodes (N = 26) compared with control lymph nodes by immunohistochemistry (IHC) for pS6, p4EBP1, and p70S6K, known effectors and readouts of mTORC1 activation. IHC for pS6 also revealed increased mTOR activation in iMCD compared with Hodgkin lymphoma, systemic lupus erythematosus, and reactive lymph nodes, suggesting that the mTOR activation in iMCD is not just a product of lymphoproliferation/inflammatory lymphadenopathy. Further, the degree of mTOR activation in iMCD was comparable to autoimmune lymphoproliferative syndrome, a disease driven by mTOR hyperactivation that responds to sirolimus treatment. Gene set enrichment analysis of serum proteomic data from iMCD patients (n = 88) and controls (n = 42) showed significantly enriched mTORC1 signaling. Finally, functional studies revealed increased baseline mTOR pathway activation in peripheral monocytes and T cells from iMCD remission samples compared with healthy controls. IL-6 stimulation augmented mTOR activation in iMCD patients, which was abrogated with JAK1/2 inhibition. These findings support mTOR activation as a novel therapeutic target for iMCD, which is being investigated through a trial of sirolimus (NCT03933904).