Factors associated with rehospitalizations of very low birthweight infants: impact of a transition home support and education program.

OBJECTIVE: To determine the effects of a transition-home education and support program, BPD, and health insurance type on VLBW infant rehospitalizations at 3 and 7 months corrected age. It was hypothesized that the transition-home program would be associated with decreased rehospitalizations between Phase 1 and 2, and public health insurance and BPD would be associated with increased rehospitalizations. METHODS: 274 infants with birth weight <1500 g were enrolled in two successive years of a transition-home program (Phase 1-start-up) and (Phase 2-full implementation) and followed to 7 months CA. RESULTS: The Phase 2 rehospitalization rates were lower but not statistically significant at both 3 months (20% and 15%; p=0.246), and 7 months (24% and 17%; p=0.171). Infants with public insurance had twice as many rehospitalizations by 3 months (28% versus 11%; p=0.018) in Phase 1. In regression analyses the intervention effects did not achieve significance for the cohort at 3 months (OR=0.63; CI=0.33 to 1.20) or 7 months (OR=0.61; CI=0.33 to 1.13). BPD and public insurance did not reach significance in the models whereas siblings were significantly associated with increased odds of rehospitalization. In subgroup analyses for infants on pubic health insurance the intervention significantly decreased the odds of rehospitalization between Phase 1 and 2(OR=0.43; CI=0.19 to 0.96) at 3 months. CONCLUSIONS: Our findings suggest that a transition-home program may be beneficial to reduce the rehospitalization rate for VLBW infants, and infants on public insurance may derive greater benefit.

First-week protein and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants.

OBJECTIVE: We sought to evaluate the association between early protein and energy intake and neurodevelopment and growth of extremely low birth weight (<1000 g) infants. STUDY DESIGN: Daily protein and energy intakes were collected by chart review for the first 4 weeks of life on 148 extremely low birth weight survivors. A total of 124 infants (84%) returned for evaluation at 18 months' corrected age. Bivariate analysis tested correlations between weekly protein or energy intakes and Bayley Mental Development Index, Psychomotor Development Index, or growth at 18 months. Separate regression models evaluated contributions of protein (grams per kilogram per day) and energy intake (kilojoules per kilogram per day) to the Mental Development Index, Psychomotor Development Index, and growth, while controlling for known confounders. RESULTS: After adjusting for confounding variables, week 1 energy and protein intakes were each independently associated with the Mental Development Index. During week 1, every 42 kJ (10 kcal)/kg per day were associated with a 4.6-point increase in the Mental Development Index and each gram per kilogram per day in protein intake with an 8.2-point increase in the Mental Development Index; higher protein intake was also associated with lower likelihood of length <10th percentile. CONCLUSIONS: Increased first-week protein and energy intakes are associated with higher Mental Development Index scores and lower likelihood of length growth restrictions at 18 months in extremely low birth weight infants. Emphasis should be placed on providing more optimal protein and energy during this first week.

Directed evolution generates a novel oncolytic virus for the treatment of colon cancer.

BACKGROUND: Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term "Directed Evolution" for creating highly potent oncolytic viruses. METHODOLOGY/PRINCIPAL FINDINGS: Taking the "Directed Evolution" approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2-3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1's efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent. CONCLUSIONS/SIGNIFICANCE: Using the "Directed Evolution" methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies.

Postnatal corticosteroids in the treatment of chronic lung disease in the preterm infant: past, present, and future.

Over the past 20 years, corticosteroid use in the preterm infant has fallen in and out offavor. Steroids were introduced in the 1980s as a mode of preventing and treating chronic lung disease (CLD) in the preterm infant population. This use has been targeted toward low birth weight infants who are unable to wean off the ventilator. Dose, duration, and timing of treatment with dexamerhasone, the steroid typically used in NICUs, has varied. This article examines why the medication has fallen out of favor and whether postnatal corticosteroids still have a place in preventing and treating CLD.