Improving Patient-Provider Continuity in a Large Urban Academic Primary Care Network.

OBJECTIVE: Although patient-provider continuity improves care delivery and satisfaction, poor continuity with primary care providers (PCP) often exists in academic centers. We aimed to increase patient empanelment from 0% to 90% and then increase the percent of well-child care (WCC) visits scheduled with the PCP from 25.6% to 50%, without decreasing timely access that might result if patients waited for PCP availability. METHODS: Nationwide Children's Hospital Primary Care Network cares for >120,000 mostly Medicaid-enrolled patients across 13 offices. Before 2017, patients were empaneled to an office, not individual PCPs. We empaneled patients to PCPs, reduced provider floating, implemented continuity-promoting scheduling guidelines, scheduled future WCC visits for patients ≤15 months during check-in for their current one, and encouraged online scheduling. We tracked the percentage of all WCC visits that were scheduled with the patient's PCP and the percentage of subsequent WCC visits for patients ≤15 months that were scheduled during the current visit, and provided feedback to schedulers. We followed emergency department (ED) utilization and visit show rates. WCC visit completion rates were tracked using HEDIS metrics. RESULTS: Patient empanelment increased from 0% to >90% (P < .001). Patient-provider WCC continuity increased from 25.6% to 54.7% (P < .001). A 20.5% decrease in ED utilization rate was associated with continuity project initiation. Empaneled patients demonstrated higher show rates (76.9%) versus unempaneled patients (71.4%; P < .001). WCC completion rates increased from 52.6% to 60.7%. CONCLUSIONS: WCC continuity more than doubled after interventions and was associated with decreased ED utilization, higher show rates, and increased timely WCC completion.

Pediatric Cotton-Tip Applicator-Related Ear Injury Treated in United States Emergency Departments, 1990-2010.

OBJECTIVE: To evaluate the characteristics of children with cotton-tip applicator (CTA)-related ear injuries. STUDY DESIGN: Data on CTA-related ear injuries among children presenting to US emergency departments (EDs) from 1990 through 2010 were obtained from the National Electronic Injury Surveillance System. RESULTS: Between 1990 and 2010, an estimated 263 338 children aged <18 years were treated for CTA-related ear injuries in US hospital EDs. There was a nonsignificant increase in the annual number of injuries from 1990 through 2001 (78.2%) and a significant decrease from 2001 through 2010 (26.0%). Younger children sustained the highest rate of injury (32.2 per 100 000 for age 0-3 years). Ear cleaning was the most frequently documented circumstance at the time of injury (73.2%), and patients themselves were most commonly handling the CTA (76.9%). Foreign body sensation (39.2%) and bleeding (34.8%) were commonly documented reasons for visiting the ED. The presence of a foreign body (29.7%) and tympanic membrane perforation (25.3%) were common diagnoses. CONCLUSION: Most CTA-related injuries occurred with children themselves handling CTAs while cleaning their ears. Foreign body and tympanic membrane perforation were the most common associated diagnoses. Despite warnings against the use of CTAs in the ear canal and use of CTAs by children, these injuries continued to occur. Additional injury prevention strategies through further parent/caregiver and child education are warranted.

Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.

We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of ß-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling.

Bioactive phytochemicals from natural products, such as black raspberries (BRB; Rubus occidentalis), have direct anticancer properties on malignant cells in culture and in xenograft models. BRB components inhibit cancer progression in more complex rodent carcinogenesis models. Although mechanistic targets for BRB phytochemicals in cancer cells are beginning to emerge, the potential role in modulating host immune processes impacting cancer have not been systematically examined. We hypothesized that BRB contain compounds capable of eliciting potent immunomodulatory properties that impact cellular mediators relevant to chronic inflammation and tumor progression. We studied both an ethanol extract from black raspberries (BRB-E) containing a diverse mixture of phytochemicals and two abundant phytochemical metabolites of BRB produced upon ingestion (Cyanidin-3-Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R). BRB-E inhibited proliferation, and viability of CD3/CD28 activated human CD4(+) and CD8(+) T lymphocytes. BRB-E also limited in vitro expansion of myeloid-derived suppressor cells (MDSC) and their suppressive capacity. Pre-treatment of immune cells with BRB-E attenuated IL-6-mediated phosphorylation of signal transducer and activator of transcription-3 (STAT3) and IL-2-induced STAT5 phosphorylation. In contrast, pre-treatment of immune cells with the C3R and Q3R metabolites inhibited MDSC expansion, IL-6-mediated STAT3 signaling, but not IL-2-induced STAT5 phosphorylation and were less potent inhibitors of T cell viability. Together these data indicate that BRB extracts and their physiologically relevant metabolites contain phytochemicals that affect immune processes relevant to carcinogenesis and immunotherapy. Furthermore, specific BRB components and their metabolites may be a source of lead compounds for drug development that exhibits targeted immunological outcomes or inhibition of specific STAT-regulated signaling pathways.

Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner.

Pancreatic stellate cells (PSC) are a subset of pancreatic cancer-associated fibroblasts. These cells provide prosurvival signals to tumors; however, little is known regarding their interactions with immune cells within the tumor microenvironment. We hypothesized that factors produced by human PSC could enhance myeloid-derived suppressor cell (MDSC) differentiation and function, which promotes an immunosuppressive microenvironment. Primary PSC cell lines (n = 7) were generated from human specimens and phenotypically confirmed via expression of vimentin, α-smooth muscle actin (α-SMA), and glial fibrillary acidic protein (GFAP). Luminex analysis indicated that PSC but not human fetal primary pancreatic fibroblast cells (HPF; negative controls) produced MDSC-promoting cytokines [interleukin (IL-6), VEGF, macrophage colony-stimulating factor (M-CSF) ] and chemokines (SDF-1, MCP-1). Culture of peripheral blood mononuclear cells [peripheral blood mononuclear cell (PBMC), n = 3 donors] with PSC supernatants or IL-6/granulocyte macrophage colony-stimulating factor (GM-CSF; positive control) for 7 days promoted PBMC differentiation into an MDSC (CD11b+CD33+) phenotype and a subpopulation of polymorphonuclear CD11b+CD33+CD15+ cells. The resulting CD11b+CD33+ cells functionally suppressed autologous T-lymphocyte proliferation. In contrast, supernatants from HPF did not induce an MDSC phenotype in PBMCs. Culture of normal PBMCs with PSC supernatants led to STAT3 but not STAT1 or STAT5 phosphorylation. IL-6 was an important mediator as its neutralization inhibited PSC supernatant-mediated STAT3 phosphorylation and MDSC differentiation. Finally, the FLLL32 STAT3 inhibitor abrogated PSC supernatant-mediated MDSC differentiation, PSC viability, and reduced autocrine IL-6 production indicating these processes are STAT3 dependent. These results identify a novel role for PSC in driving immune escape in pancreatic cancer and extend the evidence that STAT3 acts as a driver of stromal immunosuppression to enhance its interest as a therapeutic target.