Targeted Intraceptor Nanoparticle for Neovascular Macular Degeneration: Preclinical Dose Optimization and Toxicology Assessment.

Neovascular age-related macular degeneration (AMD) is treated with anti-VEGF intravitreal injections, which can cause geographic atrophy, infection, and retinal fibrosis. To minimize these toxicities, we developed a nanoparticle delivery system for recombinant Flt23k intraceptor plasmid (RGD.Flt23k.NP) to suppress VEGF intracellularly within choroidal neovascular (CNV) lesions in a laser-induced CNV mouse model through intravenous administration. In the current study, we examined the efficacy and safety of RGD.Flt23k.NP in mice. The effect of various doses was determined using fluorescein angiography and optical coherence tomography to evaluate CNV leakage and volume. Efficacy was determined by the rate of inhibition of CNV volume at 2 weeks post-treatment. RGD.Flt23k.NP had peak efficacy at a dose range of 30-60 µg pFlt23k/mouse. Using the lower dose (30 µg pFlt23k/mouse), RGD.Flt23k.NP safety was determined both in single-dose groups and in repeat-dose (three times) groups by measuring body weight, organ weight, hemoglobin levels, complement C3 levels, and histological changes in vital organs. Neither toxicity nor inflammation from RGD.Flt23k.NP was detected. No side effect was detected on visual function. Thus, systemic RGD.Flt23k.NP may be an alternative to standard intravitreal anti-VEGF therapy for the treatment of neovascular AMD.

Why providers transfuse blood products outside recommended guidelines in spite of integrated electronic best practice alerts.

BACKGROUND: Best practice alerts (BPAs) provide clinical decision support (CDS) at the point of care to reduce unnecessary blood product transfusions, yet substantial transfusions continue outside of recommended guidelines. OBJECTIVE: To understand why providers order blood transfusions outside of recommended guidelines despite interruptive alerts. DESIGN: Retrospective review. SETTING: Tertiary care hospital. PARTICIPANTS: Inpatient healthcare providers. INTERVENTION: Provider-BPA interaction data were collected from January 2011 to August 2012 from the hospital electronic medical record. MEASUREMENTS: Provider (free-text) responses to blood transfusion BPA prompts were independently reviewed and categorized by 2 licensed physicians, with agreement assessed by χ(2) analysis and kappa scoring. RESULTS: Rationale for overriding blood transfusion BPAs was highly diverse, acute bleeding being the most common (>34%), followed by protocolized behaviors on specialty services (up to 26%), to "symptomatic" anemia (11%-12%). Many providers transfused in anticipation of surgical or procedural intervention (10%-15%) or imminent hospital discharge (2%-5%). Resident physicians represented the majority (55%) of providers interacting with BPAs. CONCLUSION: Providers interacting with BPAs (primarily residents and midlevel providers) often do not have the negotiating power to change ordering behavior. Protocolized behaviors, unlikely to be influenced by BPAs, are among the most commonly cited reasons for transfusing outside of guidelines. Symptomatic anemia is a common, albeit subjective, indication cited for blood transfusion. With a wide swath of individually uncommon rationales for transfusion behavior, secondary use of electronic medical record databases and integrated CDS tools are important to efficiently analyze common practice behaviors.

Cost and turn-around time display decreases inpatient ordering of reference laboratory tests: a time series.

OBJECTIVE: Reference tests, also known as send-out tests, are commonly ordered laboratory tests with variable costs and turn-around times. We aim to examine the effects of displaying reference laboratory costs and turn-around times during computerised physician order entry (CPOE) on inpatient physician ordering behaviour. DESIGN: We conducted a prospective observational study at a tertiary care hospital involving inpatient attending physicians and residents. Physician ordering behaviour was prospectively observed between September 2010 and December 2012. An intervention was implemented to display cost and turn-around time for reference tests within our CPOE. We examined changes in the mean number of monthly physician orders per inpatient day at risk, the mean cost per order, and the average turn-around time per order. RESULTS: After our intervention, the mean number of monthly physician orders per inpatient day at risk decreased by 26% (51 vs 38, p<0.0001) with a decrease in mean cost per order (US$146.50 vs US$134.20, p=0.0004). There were no significant differences in mean turn-around time per order (5.6 vs 5.7 days, p=0.057). A stratified analysis of both cost and turn-around time showed significant decreases in physician ordering. The intervention projected a mean annual savings of US$330 439. Reference test cost and turn-around time variables were poorly correlated (r=0.2). These findings occurred in the setting of non-significant change to physician ordering in a control cohort of non-reference laboratory tests. CONCLUSIONS: Display of reference laboratory cost and turn-around time data during real-time ordering may result in significant decreases in ordering of reference laboratory tests with subsequent cost savings.