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Purpose To investigate intraocular pharmacokinetics of 10-fold dose of intravitreally injected ranibizumab compared with the conventional dose in an experimental model. Methods Ranibizumab 30 µL at 10 mg/mL (conventional) and 100 mg/mL (10-fold) doses was injected separately into each eye of 28 rabbits. Ranibizumab concentrations in the aqueous humor, vitreous, and retina were estimated at each time period after injection, using enzyme-linked immunosorbent assay. The pharmacokinetic properties of ranibizumab were determined using a one-compartment model in all three ocular tissues. The time-concentration profile and predictive trends were plotted to determine drug efficacy in the retina. Results Maximum concentrations after conventional and 10-fold dosing were observed in the retina at 1 and 4 days after injection, respectively. The half-life of ranibizumab after conventional and 10-fold dosing did not differ in the anterior chamber and vitreous, whereas the half-life was prolonged approximately twice with the 10-fold dose in the retina (36.74 h vs. 76.85 h) and serum (91.93 h vs. 179.01 h). Similarly, the estimated time for ranibizumab concentration in the retina over 27 ng/mL (minimum effective concentration of ranibizumab) was prolonged approximately twice with the 10-fold dose (1315 h [55 days] vs. 2393 h [100 days]). No adverse effects were observed in either group. Conclusions The retinal half-life and concentration of ranibizumab in rabbit eyes were increased approximately twice after a 10-fold dose compared with the conventional dose. This finding indicates a possibility to lengthen the injection interval to improve the efficacy of ranibizumab in human eyes. Translational relevance Our results highlight the potential for clinical application of a high-dose (10-fold) of anti-VEGF agents to prolong the intravitreal injection intervals, simultaneously improving the drug efficacy.

Purpose: Volunteer service learning activities, including Student Run Clinics (SRCs), are becoming an increasingly popular extracurricular component of medical education. While there are reports that student clinicians generally enjoy their educational experiences at SRCs, it is not understood how to optimize and measure student engagement in them. To identify key drivers of student engagement a tool was created to measure volunteer experience at the Crimson Care Collaborative (CCC), a primary care SRC. Methods: CCC volunteers were asked to complete an online engagement survey. Cross-sectional survey data were collected for 149 CCC volunteers (53% response rate). Results: Multivariate linear regression showed that overall ‘likelihood to recommend CCC to a friend’ was significantly associated with students’ perception of the clarity of their role within the clinic, frequency of interprofessional interactions, and overall quality of medical education. Students who volunteer more frequently and for longer periods of time had higher engagement scores. Conclusions: Measuring engagement is feasible in volunteer settings. Engagement appears to be dependent on both structural and experiential components. Easily modifiable components of job design (role definition, expected frequency of volunteering), are key drivers of volunteer engagement.

Purpose Seasonal influenza vaccination is recommended in children aged 6–59 months, but little is known about child vaccination coverage and determinants in Asian settings. We report the results of a survey of knowledge, attitudes, practices, and determinants of child influenza vaccination in Singapore. Methods In December 2015-March 2016, we conducted a survey of 332 parents of children aged 6 months to 5 years attending pre-schools. We assessed child influenza vaccine coverage and parental knowledge, attitudes, and practices of child influenza vaccination. We used multivariable regression and structural equation models to identify factors associated with child influenza vaccination. Results Knowledge about influenza, perceived benefit of vaccination, and willingness to vaccinate were high. However, only 32% of children had ever received influenza vaccine, and only 15% in the past year. Factors independently associated with child influenza vaccination included: being recommended influenza vaccine by a child’s doctor (prevalence ratio (PR) = 2.47, 95% CI: 1.75–3.48); receiving influenza vaccine information from a private general practitioner (PR = 1.47, 95% CI: 1.05–2.04); regularly receiving pre-travel influenza vaccine (PR = 1.64, 95% CI: 1.19–2.25); higher willingness to vaccinate (PR = 1.58, 95% CI:1.24–2.04 per unit increase in willingness score); and feeling well-informed about influenza vaccine (PR = 1.44, 95% CI: 1.04–1.99). Parents who obtained influenza vaccine information from television were less likely to have vaccinated their child (PR = 0.44, 95% CI: 0.23–0.85). Path analysis indicated that being recommended vaccination by a child's doctor increased willingness to vaccinate and self-efficacy (feeling well-informed about influenza vaccine). Median willingness-to-pay for a dose of influenza vaccine was SGD30 (interquartile range: SGD20-SGD50), and was higher in parents of vaccinated compared with unvaccinated children (SGD45 vs SGD30, p = 0.0012). Conclusion Knowledge and willingness to vaccinate was high in this parent population, but influenza vaccine uptake in children was low. Encouraging medical professionals to recommend vaccination of eligible children is key to improving uptake.