Pro-inflammatory immune responses in leukocytes of premature infants exposed to maternal chorioamnionitis or funisitis.

BACKGROUND: Acute chorioamnionitis contributes to premature birth, and is associated with postbirth complications. How chorioamnionitis impacts neonate's developing immune system has not been well defined. METHODS: Blood from extremely preterm infants (≤28 wk gestation) was drawn at the first, second, and fourth week of life. Blood was either left unstimulated or stimulated for 4 h with PMA/ionomycin. mRNA expression of transcription factors in unstimulated cells (RORC, TBET, GATA3, and Forkhead box protein 3 (FOXP3)) and inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, and IL-6) in unstimulated and stimulated cells were analyzed. Data were analyzed based on the diagnosis of chorioamnionitis, funisitis and bronchopulmonary dysplasia (BPD). RESULTS: At 1 wk of life, exposure to funisitis, but not maternal chorioamnionitis was associated with an increased expression of RORC and RORC/FOXP3 ratio. These increases in RORC and RORC/FOXP3 ratio were sustained over the 4 wk of follow-up. Leukocytes from infants who developed BPD had increased stimulated and unstimulated IL-4 at the first week of life, but these increases were not sustained over time. In contrast, infants with mild BPD had a sustained decrease in stimulated IL-2. CONCLUSION: Chorioamnionitis exposure, in particular to funisitis, lead to enhanced Th17-like responses that persist for 4 wk after birth. Infants who later developed BPD did not exhibit a strikingly distinct immune profile.

Development and implementation of ambulatory care pharmacy services at an internal medicine clinic.

PURPOSE: This report describes the step-by-step process that led to expansion of ambulatory care pharmacy services at a newly established internal medicine clinic within a patient-centered medical home in North Carolina. SUMMARY: Implementation of clinical pharmacist services at the clinic was led by a postgraduate year 2 (PGY2) pharmacy resident and guided by the 9 steps described in the book Building a Successful Ambulatory Care Practice: A Complete Guide for Pharmacists. After a needs assessment and review of the demographics and insurance status of the clinic's target population, it was determined that pharmacist services would focus on quality measures including diabetes nephropathy screening, diabetes eye examination, blood glucose control in diabetes, discharge medication reconciliation, annual wellness visits, and medication adherence in diabetes, hypercholesterolemia, and hypertension. Clinic appointments were conducted under 3 models: a pharmacist-physician covisit model, a "floor model" of pharmacist consultation on drug information or medication management issues during medical resident sign-out sessions with supervising physicians (medical residents could also see patients along with the pharmacist at a covisit appointment), and a covisit model of stacked physician and pharmacist appointments. The pharmacist's services were expanded from 2 half-day clinic sessions per week initially to 5 or 6 half-day clinic sessions by the end of the residency year. CONCLUSION: By the fourth quarter of the first PGY2 residency year in which ambulatory care pharmacy services were provided in the clinic, the clinical and financial impact of those services justified the addition of a second full-time pharmacist to the clinic team.

Comprehensive and Collaborative Pharmacist Transitions of Care Service for Underserved Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Mortality risk from chronic obstructive pulmonary disease (COPD) increases significantly in the first year after a 30-day hospital readmission. OBJECTIVE: To evaluate a comprehensive and collaborative pharmacist transitions of care service for patients hospitalized with COPD compared to usual care. METHODS: In this within-site, retrospective study, discharge counseling, medication reconciliation, medication access assistance, therapy changes, and post-discharge long-term follow-up were provided to underserved adult patients with a primary care provider at the study clinic and admitted to the affiliated hospital with a primary diagnosis of COPD exacerbation. Primary outcome was a 180-day composite of COPD-related hospitalizations and emergency department (ED) visits. Secondary outcomes were 30-, 60-, 90-, and 180-day events, costs, pharmacist interventions, time to follow-up, and pneumonia. RESULTS: Sixty-five patients were identified with a total of 101 index admissions. The mean age was 62.5 years, approximately 55.3% were female, and 67.7% were black or African American. The primary composite was significantly lower in the pharmacist intervention group compared to usual care (mean difference 0.82, P=0.0364, 95% confidence interval [CI] 0.05-1.60), driven by lower 30-day hospitalizations in the intervention group (mean difference 0.15, P=0.0099, 95% CI 0.04-0.27). Cost associated with COPD-related hospitalizations was significantly lower in the pharmacist intervention group compared to usual care ($173,808, P = 0.0330) as well as before intervention ($79,662, P=0.0233). There was no significant difference in time to follow-up or pneumonia. CONCLUSIONS: A comprehensive, collaborative pharmacist transitions of care service significantly reduced 30-day COPD-related hospital readmissions, ED re-visits, and associated costs in an underserved population.

Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants.

OBJECTIVE: To determine whether exposure to acute chorioamnionitis and fetal inflammation caused short-term adverse outcomes. DESIGN: This is a prospective observational study: subjects were mothers delivering at 32-36 weeks gestation and their preterm infants at a large urban tertiary level III perinatal unit (N=477 infants). Placentae and fetal membranes were scored for acute histological chorioamnionitis based on the Redline criteria. Fetal inflammation was characterised by histological diagnosis of funisitis (umbilical cord inflammation), increased cord blood cytokines measured by ELISA, and activation of the inflammatory cells infiltrating the placenta and fetal membranes measured by immunohistology. Maternal and infant data were collected. RESULTS: Twenty-four per cent of 32-36-week infants were exposed to histological chorioamnionitis and 6.9% had funisitis. Immunostaining for leucocyte subsets showed selective infiltration of the placenta and fetal membranes with activated neutrophils and macrophages with chorioamnionitis. Interleukin (IL) 6, IL-8 and granulocyte colony-stimulating factor were selectively increased in the cord blood of preterm infants with funisitis. Compared with infants without chorioamnionitis, funisitis was associated with increased ventilation support during resuscitation (43.8% vs 15.4%) and more respiratory distress syndrome postnatally (27.3% vs 10.2%) in univariate analysis. However, these associations disappeared after adjusting for prematurity. CONCLUSIONS: Despite fetal exposure to funisitis, increased cord blood cytokines and activated placental inflammatory cells, we could not demonstrate neonatal morbidity specifically attributable to fetal inflammation after adjusting for gestational age in moderate and late preterm infants.

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates.

Regulatory T-cells (Treg) have a protective role for the control of immune activation and tissue damage. The effects of chorioamnionitis (chorio) on Treg in moderate/late preterm newborns are not known. We hypothesized that infants exposed to chorio would have decreased Treg frequency and/or function. We isolated mononuclear cells from adult peripheral blood and cord blood from term and moderate/late preterm infants who were classified for severity of chorio exposure. Mononuclear cells were analyzed by flow cytometry for Treg frequency and phenotype. Treg suppression of activation of conventional T-cells (Tcon) was also quantified. Treg frequencies were similar in all groups of neonates, but lower than that found in adults. Newborn Treg had a naïve phenotype, with decreased levels of CD45RO, HLA-DR, CD39 and TIGIT compared to adult Treg and chorio did not affect the phenotype. Treg from preterm newborns exposed to severe chorio had higher expression of Ki67 compared to the other groups. Treg from preterm newborns were less suppressive than Treg from adults or term, and the level of suppression was reduced with severe chorio. Relative to term, Treg frequency and phenotype were not affected by prematurity and chorio but their functionality was decreased. Lower Treg activity may contribute to inflammation in newborns that is often associated with chorioamnionitis.