Health literacy of parents of very preterm infants at NICU admission and discharge: a prospective cohort study.

OBJECTIVE: To determine the prevalence of limited health literacy in parents of infants born ≤32 and 0/7 weeks and if health literacy changes during hospitalization. STUDY DESIGN: Multi-site, prospective cohort study measuring health literacy using the Parent Health Literacy Activities Test, which estimates caregivers' ability to complete tasks such as reading prescription labels and preparing bottles. Data were analyzed using parametric and nonparametric comparison tests and multivariable regression to control for confounders. RESULT: Of the 137 participants, 31% missed ≥3 questions of 8. Scores were not associated with admission characteristics or NICU complications. Lower scores were associated with lower nurses' (rho 0.20, p = 0.04) but not parents' (rho -0.12, p = 0.22) ratings of discharge readiness. Scores improved slightly from admission to discharge (p = 0.049). CONCLUSION: Many parents have difficulty answering questions related to basic infant care tasks. NICUs should ensure that communication and discharge planning are mindful of health literacy.

Continuity of Care in Infancy and Early Childhood Health Outcomes.

BACKGROUND AND OBJECTIVES: Continuity of care is a key aspect of the patient-centered medical home and improves pediatric outcomes. Health care reform requires high-quality data to demonstrate its continued value. We hypothesized that increased provider continuity in infancy will reduce urgent health care use and increase receipt of preventive services in early childhood. METHODS: Continuity, using the Usual Provider of Care measure, was calculated across all primary care encounters during the first year of life in a prospectively-constructed cohort of 17 773 infants receiving primary care from birth through 3 years at 30 clinics. Health care utilization and preventive care outcomes were measured from ages 1 to 3 years. Confounders, including chronic conditions, number of sick visits in the first year, socioeconomic status, and site, were addressed by using multivariable regression models incorporating a propensity score. RESULTS: Demographics associated with the lowest continuity quartile included white race (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.25-1.64), Medicaid insurance (aOR 1.41; 95% CI 1.23-1.61), and asthma (aOR 1.59; 95% CI 1.30-1.93). Lower continuity was associated with more ambulatory care-sensitive hospitalizations (adjusted incidence rate ratio 2.74; 95% CI 1.49-5.03), ambulatory sick visits (adjusted incidence rate ratio 1.08; 95% CI 1.05-1.11), and lower odds of lead screening (aOR 0.61; 95% CI 0.46-0.79). These associations were stronger for children with chronic conditions. Continuity measured during well visits was not associated with outcomes. CONCLUSIONS: Continuity may improve care quality and prevent high-cost health encounters, especially for children with chronic conditions. Novel solutions are needed to improve continuity in the medical home.

Perspectives of Low Socioeconomic Status Mothers of Premature Infants.

BACKGROUND AND OBJECTIVES: Transitioning premature infants from the NICU to home is a high-risk period with potential for compromised care. Parental stress is high, and families of low socioeconomic status may face additional challenges. Home visiting programs have been used to help this transition, with mixed success. We sought to understand the experiences of at-risk families during this transition to inform interventions. METHODS: Mothers of infants born at <35 weeks' gestation, meeting low socioeconomic status criteria, were interviewed by telephone 30 days after discharge to assess caregiver experiences of discharge and perceptions of home visitors (HVs). We generated salient themes by using grounded theory and the constant comparative method. Interviews were conducted until thematic saturation was achieved. RESULTS: Twenty-seven mothers completed interviews. Eighty-five percent were black, and 81% had Medicaid insurance. Concern about infants' health and fragility was the primary theme identified, with mothers reporting substantial stress going from a highly monitored NICU to an unmonitored home. Issues with trust and informational consistency were mentioned frequently and could threaten mothers' willingness to engage with providers. Strong family networks and determination compensated for limited economic resources, although many felt isolated. Mothers appreciated HVs' ability to address infant health but preferred nurses over lay health workers. CONCLUSIONS: Low-income mothers experience significant anxiety about the transition from the NICU to home. Families value HVs who are trustworthy and have relevant medical knowledge about prematurity. Interventions to improve transition would benefit by incorporating parental input and facilitating trust and consistency in communication.

Every three-hour versus every six-hour oral feeding in preterm infants: a randomised clinical trial.

AIM: This trial compares two oral feeding schedules, every three-hour and every six-hour oral feeding attempts, to determine which schedule allows for more rapid attainment of full oral feeding in preterm infants. METHODS: Infants born at ≤33-week gestation were randomly assigned to receive oral feeding every three hours or every six hours if feeding cues were present. The primary outcome was time to full oral feeding; secondary outcomes include respiratory and apnoea rates, growth and length of stay. RESULTS: A total of 55 infants were recruited. There was no difference between the groups in the primary or secondary outcomes. CONCLUSION: For preterm infants fed when oral feeding cues are present, an every six-hour schedule did not alter the time to full oral feeding and had no effect on rates of tachypnoea, apnoea or length of hospital stay compared to every three-hour feeding schedule. An every six-hour oral feeding schedule led to only small reductions in number of oral feeding attempts per day.

Mucus-penetrating nanoparticles made with "mucoadhesive" poly(vinyl alcohol).

Nanoparticles that readily penetrate mucosal layers are desirable for a variety of biomedical applications. Nevertheless, most nanoparticles tend to be immobilized in mucus via steric and/or adhesive interactions. Contrary to the established opinion that poly(vinyl alcohol) (PVA) is mucoadhesive, we discovered that coating otherwise mucoadhesive nanoparticles with certain partially hydrolyzed PVAs can aid particle mobility in mucus. We describe two approaches to producing such mucus-penetrating particles (non-covalent modification of pre-formed nanoparticles and emulsification in the presence of PVA) and provide mobility data in human cervicovaginal mucus ex vivo as measured by multiple particle tracking and bulk permeation. When coated with PVAs that are ≥95% hydrolyzed, nanoparticles as small as ~210nm were immobilized in mucus similarly to well-established mucoadhesive controls (P>0.05). However, nanoparticles coated with PVAs that are <95% hydrolyzed penetrated mucus with velocities significantly exceeding those for the mucoadhesive controls (P<0.001) and were mobile in the bulk permeation assay.

Sustained Pulmonary Delivery of a Water-Soluble Antibiotic Without Encapsulating Carriers.

PURPOSE: Traditional polymeric nanoparticle formulations for prolonged local action during inhalation therapy are highly susceptible to muco-ciliary clearance. In addition, polymeric carriers are typically administered in high doses due to finite drug loading. For toxicological reasons, these carriers and their degradation byproducts are undesirable for inhalation therapy, particularly for chronic use, due to potential lung accumulation. METHODS: We synthesized a novel, insoluble prodrug (MRPD) of a time-dependent ß-lactam, meropenem, and formulated MRPD into mucus-penetrating crystals (MRPD-MPCs). After characterizing their mucus mobility (in vitro) and stability, we evaluated the lung pharmacokinetics of intratracheally-instilled MRPD-MPCs and a meropenem solution in guinea pigs. RESULTS: Meropenem levels rapidly declined in the lungs of guinea pigs receiving meropenem solution compared to those given MRPD-MPCs. At 9 h after dosing, drug levels in the lungs of animals that received meropenem solution dropped to 12 ng/mL, whereas those that received MRPD-MPCs maintained an average drug level of ≥1,065 ng/mL over a 12-h period. CONCLUSIONS: This work demonstrated that the combination of prodrug chemistry and mucus-penetrating platform created nanoparticles that produced sustained levels of meropenem in guinea pig lungs. This strategy represents a novel approach for sustained local drug delivery to the lung without using encapsulating matrices.

The role of social determinants in explaining racial/ethnic disparities in perinatal outcomes.

In the United States, there continue to be significant racial/ethnic disparities in preterm birth (PTB) rates, infant mortality, and fetal mortality rates. One potential mediator of these disparities is social determinants of health, including individual socioeconomic factors; community factors such as crime, poverty, housing, and the racial/ethnic makeup of the community; and the physical environment. Previous work has identified statistically significant associations between each of these factors and adverse pregnancy outcomes. However, there are recent studies that provide new, innovative insights into this subject, including adding social determinant data to population-based datasets; exploring multiple constructs in their analysis; and examining environmental factors. The objective of this review will be to examine this recent research on the association of each of these sets of social determinants on racial/ethnic disparities PTB, infant mortality, and fetal mortality to highlight potential areas for targeted intervention to reduce these differences.

Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles.

PURPOSE: Enhanced drug exposure to the ocular surface typically relies on inclusion of viscosity-enabling agents, whereas delivery to the back of the eye generally focuses on invasive means, such as intraocular injections. Using our novel mucus-penetrating particle (MPP) technology, which rapidly and uniformly coats and penetrates mucosal barriers, we evaluated if such drug formulations could increase ocular drug exposure and improve topical drug delivery. METHODS: Pharmacokinetic (PK) profiling of topically administered loterprednol etabonate formulated as MPP (LE-MPP) was performed in rabbits and a larger species, the mini-pig. Pharmacodynamic evaluation was done in a rabbit model of VEGF-induced retinal vascular leakage. Cellular potency and PK profile were determined for a second compound, KAL821, a novel receptor tyrosine kinase inhibitor (RTKi). RESULTS: We demonstrated in animals that administration of LE-MPP increased exposure at the ocular surface and posterior compartments. Furthermore using a rabbit vascular leakage model, we demonstrated that biologically effective drug concentrations of LE were delivered to the back of the eye using the MPP technology. We also demonstrated that a novel RTKi formulated as MPPs provided drug levels to the back of the eye above its cellular inhibitory concentration. CONCLUSIONS: Topical dosing of MPPs of LE or KAL821 enhanced drug exposure at the front of the eye, and delivered therapeutically relevant drug concentrations to the back of the eye, in animals. TRANSLATIONAL RELEVANCE: These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases.

Ocular Pharmacokinetics of a Novel Loteprednol Etabonate 0.4% Ophthalmic Formulation.

INTRODUCTION: Topical ophthalmic formulations of corticosteroids are commonly used to treat a variety of ocular diseases and conditions that have an inflammatory component. The purpose of this study was to evaluate the effect of the mucus-penetrating particle (MPP) technology on the pharmacokinetic profile of loteprednol etabonate in the ocular tissues of rabbits. METHODS: Forty-eight New Zealand White rabbits were randomly assigned to two groups (n = 3 rabbits or 6 eyes per time point) and treated with either the novel loteprednol etabonate MPP suspension formulation, 0.4% (LE-MPP 0.4%), or the commercial Lotemax(®)-brand loteprednol etabonate ophthalmic suspension, 0.5% (Lotemax 0.5%) (Bausch & Lomb Incorporated, Inc., Rochester, NY, USA). Samples of aqueous humor, various ocular tissues, and plasma were collected from animals over a 12-h period after a single dose of the test articles. Loteprednol etabonate concentrations were assayed using liquid chromatography-tandem mass spectrometry (LC/MS/MS). RESULTS: Loteprednol etabonate was rapidly absorbed into ocular tissues following administration of either formulation. A higher ocular exposure was achieved using LE-MPP 0.4%, with peak concentrations of approximately threefold higher in ocular tissues and the aqueous humor than Lotemax 0.5%. CONCLUSIONS: Administration of LE-MPP 0.4% improved loteprednol etabonate pharmacokinetic profile in ocular tissues of rabbits. The results of this study support the premise that the MPP technology can be used to enhance ocular exposure for topically applied therapeutic agents. Further studies to assess the clinical efficacy and safety of the LE-MPP formulation are warranted.

Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft.

The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently led to increased tumor exposure of Docetaxel from 0 to 168h (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. FROM THE CLINICAL EDITOR: In this study, the plasma, tumor, and tissue pharmacokinetics of different Docetaxel nanoparticles of precise shape and size were characterized in mice with human ovarian carcinoma xenograft. It is concluded that the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system.

Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer.

Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32-46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer.

Potent engineered PLGA nanoparticles by virtue of exceptionally high chemotherapeutic loadings.

Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT (particle replication in nonwetting templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere.

Discrimination of nylon polymers using attenuated total reflection mid-infrared spectra and multivariate statistical techniques.

Nylons are an important class of synthetic polymers, from an industrial, as well as forensic, perspective. A spectroscopic method, such as Fourier transform infrared (FT-IR) spectroscopy, is necessary to determine the nylon subclasses (e. g., nylon 6 or nylon 6,6). Library searching using absolute difference and absolute derivative difference algorithms gives inconsistent results for identifying nylon subclasses. The objective of this study was to evaluate the usefulness of peak ratio analysis and multivariate statistics for the identification of nylon subclasses using attenuated total reflection (ATR) spectral data. Many nylon subclasses could not be distinguished by the peak ratio of the N-H vibrational stretch to the sp(3) C-H(2) vibrational stretch intensities. Linear discriminant analysis, however, provided a graphical visualization of differences between nylon subclasses and was able to correctly classify a set of 270 spectra from eight different subclasses with 98.5% cross-validated accuracy.