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.

Impact of Janani Suraksha Yojana on institutional delivery rate and maternal morbidity and mortality: an observational study in India.

The Government of India initiated a cash incentive scheme--Janani Suraksha Yojana (JSY)--to promote institutional deliveries with an aim to reduce maternal mortality ratio (MMR). An observational study was conducted in a tertiary-care hospital of Madhya Pradesh, India, before and after implementation of JSY, with a sample of women presenting for institutional delivery. The objectives of this study were to: (i) determine the total number of institutional deliveries before and after implementation of JSY, (ii) determine the MMR, and (iii) compare factors associated with maternal mortality and morbidity. The data were analyzed for two years before implementation of JSY (2003-2005) and compared with two years following implementation of JSY (2005-2007). Overall, institutional deliveries increased by 42.6% after implementation, including those among rural, illiterate and primary-literate persons of lower socioeconomic strata. The main causes of maternal mortality were eclampsia, pre-eclampsia and severe anaemia both before and after implementation of JSY. Anaemia was the most common morbidity factor observed in this study. Among those who had institutional deliveries, there were significant increases in cases of eclampsia, pre-eclampsia, polyhydramnios, oligohydramnios, antepartum haemorrhage (APH), postpartum haemorrhage (PPH), and malaria after implementation of JSY. The scheme appeared to increase institutional delivery by at-risk mothers, which has the potential to reduce maternal morbidity and mortality, improve child survival, and ensure equity in maternal healthcare in India. The lessons from this study and other available sources should be utilized to improve the performance and implementation of JSY scheme in India.

Financial incentives to influence maternal mortality in a low-income setting: making available 'money to transport' - experiences from Amarpatan, India.

OBJECTIVES: Only 40.7% women in India deliver in an institution; leaving many vulnerable to maternal morbidity and mortality (India has 22% of global maternal deaths). While limited accessibility to functioning institutions may account in part, a common reason why women deliver at home is poverty. A lack of readily available financial resources for families to draw upon at the time of labor to transport the mother to an institution, is often observed. This paper reports a yearlong collaborative intervention (between the University and Department of Health) to study if providing readily available and easily accessible funds for emergency transportation would reduce maternal deaths in a rural, low income, and high maternal mortality setting in central India. It aimed to obviate a deterrent to emergency obstetric care; the non-availability of resources with mothers when most needed. Issues in implementation are also discussed. METHODS: Maternal deaths were actively identified in block Amarpatan (0.2 million population) over a 2-year period. The project, with participation from local government and other groups, trained 482 local health care providers (public and private) to provide antenatal care. Emergency transport money (in cash) was placed with one provider in each village. Maternal mortality in the adjacent block (Maihar) was followed (as a 'control' block). RESULTS: Maternal deaths in Amarpatan decreased during the project year relative to the previous year, or in the control block the same year. DISCUSSION AND CONCLUSIONS: Issues in implementation of the cash incentive scheme are discussed. Although the intervention reduced maternal deaths in this low-income setting, chronic poverty and malnutrition are underlying structural problems that need to be addressed.