Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets.

Pancreatic islet transplantation holds great potential as a curative therapy for treating type 1 diabetes. However, the need for lifelong systemic immunosuppression with inevitable side effects is an obstacle to clinical success. Here we devised a strategy for the site-specific delivery of an immunosuppressant (tacrolimus) using layer-by-layer assembly of polymeric particles and collagen on the islet surface. This approach aims to provide a continuous and sustained supply of tacrolimus in the vicinity of transplanted cells while avoiding systemic drug exposure. The dose and release rate of tacrolimus can be tunable to achieve therapeutic windows by varying layer-by-layer construction and chemistry of polymers. Transplanting 400 IEQ of pancreatic islets coated with particles containing ∼3 µg of TAC per recipient provided controlled drug release and rectified diabetes for up to 5 months in a xenogeneic rodent model of type 1 diabetes. We anticipate that the findings of this study will be found useful by those developing local immunomodulation strategies aimed at improving the outcomes and safety of cell therapies for curing type 1 diabetes.

Referral patterns, delays, and equity in access to advanced paediatric emergency care in Vietnam.

BACKGROUND: Quality emergency care is a critical component of a well-functioning health system. However, severely ill children often face barriers to timely, appropriate care in less-developed health systems. Such barriers disproportionately affect poorer children, and may be particularly acute when children seek advanced emergency care. We examine predictors of increased acuity and patient outcomes at a tertiary paediatric emergency department to identify barriers to advanced emergency care among children. METHODS: We analysed a sample of 557 children admitted to a paediatric referral hospital in Hanoi, Vietnam. We examined associations between socio-demographic and facility characteristics, referrals and transfers, and patient outcomes. We used generalized ordered logistic regression to examine predictors of increased acuity on arrival. RESULTS: Most children accessing advanced emergency care were under two years of age (68.4%). Pneumonia was the most prevalent diagnosis (23.7%). Children referred from lower-level facilities experienced higher acuity on arrival (p = .000), were more likely to be admitted to an ICU (p = .000), and were more likely to die during hospitalization (p = .009). The poorest children [OR = 4.98, (1.82-13.61)], and children entering care at provincial hospitals [OR = 3.66, (2.39-5.63)] and other lower-level facilities [OR = 3.24, (1.78-5.88)] had significantly higher odds of increased acuity on arrival. CONCLUSIONS: The poorest children, who were more likely to enter care at lower-level facilities, were especially disadvantaged. While delays in entry to care were not predictive of acuity, children referred to tertiary care from lower-level facilities experienced worse outcomes. Improvements in triage, stabilization, and referral linkages at all levels should reduce within-system delays, increasing timely access to advanced emergency care for all children.