Background Effective colorectal cancer screening depends on timely diagnostic evaluation in patients with abnormal fecal immunochemical tests (FIT). Although prior studies suggest low rates of follow-up colonoscopy, there is little information among patients in safety-net health systems and few data characterizing reasons for low follow-up rates. Aims Characterize factors contributing to lack of follow-up colonoscopy in a racially diverse and socioeconomically disadvantaged cohort of patients with abnormal FIT receiving care in an integrated safety-net health system. Methods We performed a retrospective electronic medical record review of patients aged 50-64 years with abnormal FIT at a population-based safety-net health system between January 2010 and July 2013. Review of electronic medical record focused on patients without follow-up colonoscopy to characterize patient-, provider-, and system-level reasons for lack of diagnostic evaluation. We used logistic regression analysis to identify predictors of follow-up colonoscopy within 12 months of abnormal FIT. Results Of 1267 patients with abnormal FIT, 536 (42.3%) failed to undergo follow-up colonoscopy within one year. Failure was attributable to patient-level factors in 307 (57%) cases, provider factors in 97 (18%) cases, system factors in 118 (22%) cases. In multivariate analysis, follow-up colonoscopy was less likely among those aged 61-64 years (OR 0.63, 95%CI 0.46–0.87) compared to 50-55 year-olds. Conclusions Nearly half (42%) of patients with abnormal FIT failed to undergo follow-up colonoscopy within one year. Lack of diagnostic evaluation is related to a combination of patient-, provider-, and system-level factors, highlighting the need for multi-level interventions to improve follow-up colonoscopy completion rates.
This study provides evidence to support that albumin nanoparticles are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs are a novel delivery system against lung injury with potential antioxidant activity.
a b s t r a c tThe potential of amphiphilic chitosan formed by grafting octanoyl chains on the chitosan backbone for pulmonary delivery of levofloxacin has been studied. The success of polymer synthesis was confirmed using FT-IR and NMR, whilst antimicrobial activity was assessed against Pseudomonas aeruginosa. Highly dispersible dry powders for delivery as aerosols were prepared with different amounts of chitosan and octanoyl chitosan to study the effect of hydrophobic modification and varying concentration of polymer on aerosolization of drug. Powders were prepared by spray-drying from an aqueous solution containing levofloxacin and chitosan/amphiphilic octanoyl chitosan. L-leucine was also used to assess its effect on aerosolization. Following spray-drying, the resultant powders were characterized using scanning electron microscopy, laser diffraction, dynamic light scattering, HPLC, differential scanning calorimetry, thermogravimetric analysis and X-ray powder diffraction. The in vitro aerosolization profile was determined using a Next Generation Impactor, whilst in vitro antimicrobial assessment was performed using MIC assay. Microparticles of chitosan have the property of mucoadhesion leading to potential increased residence time in the pulmonary mucus, making it important to test the toxicity of these formulations. In-vitro cytotoxicity evaluation using MTT assay was performed on A549 cell line to determine the toxicity of formulations and hence feasibility of use. The MTT assay confirmed that the polymers and the formulations were non-cytotoxic. Hydrophobically modifying chitosan showed significantly lower MIC (4-fold) than the commercial chitosan against P. aeruginosa. The powders generated were of suitable aerodynamic size for inhalation having a mass median aerodynamic diameter less than 4.5 lm for formulations containing octanoyl chitosan. These highly dispersible powders have minimal moisture adsorption and hence an emitted dose of more than 90% and a fine particle fraction (FPF) of 52%. Powders with non-modified chitosan showed lower dispersibility, with an emitted dose of 72% and FPF of 20%, as a result of high moisture adsorption onto the chitosan matrix leading to cohesiveness and subsequently decreased dispersibility.
Objective Examine parental perspectives/rankings of the most important weight-management clinical practices; and, determine whether preferences/rankings differ when parents disagree that their child is overweight. Methods Mixed-methods analysis of a 32-question survey of parents of 2-18 year-old overweight children assessing parental agreement that their child is overweight, the single most important thing providers can do to improve weight status, ranking AAP-recommended clinical practices, and preferred follow-up interval. Four independent reviewers analyzed open-response data to identify qualitative themes/subthemes. Multivariable analyses examined parental rankings, preferred follow-up interval, and differences by agreement with their child’s overweight assessment. Results Thirty-six percent of 219 children were overweight, 42% were obese, and 22% severely obese; 16% of parents disagreed with their child’s overweight assessment. Qualitative analysis of the most important practice to help overweight children yielded 10 themes; unique to parents disagreeing with their children’s overweight assessments was, “change weight-status assessments.” After adjustment, the three highest-ranked clinical practices included, “check for weight-related problems,” “review growth chart,” and “recommend general dietary changes” (all P<.01);” parents disagreeing with their children’s overweight assessments ranked “review growth chart” as less important, and “reducing screen time” and “general activity changes” as more important. The mean preferred weight-management follow-up interval (10-12 weeks) did not differ by agreement with children’s overweight assessments. Conclusions Parents prefer weight-management strategies that prioritize evaluating weight-related problems, growth-chart review, and regular follow-up. Parents who disagree that their child is overweight want changes in how overweight is assessed. Using parent-preferred weight-management strategies may prove useful in improving child weight status.
Nucleobase-containing isoxazolidines spiro-bonded to an indane core have been synthesized in very good yields by regio- and diastereoselective 1,3-dipolar cycloaddition starting from indanyl nitrones and N-vinylnucleobases by using environmentally benign microwave technology. The contemporary presence of various structural groups that are individually active scaffolds of different typology of drugs, has directed us to speculate that these compounds may act as inhibitors of MDM2–p53 interaction. Therefore, both computational calculations and antiproliferative screening against A549 human lung adenocarcinoma cells and human SH-SY5Y neuroblastoma cells were carried out to support this hypothesis.
A B S T R A C TPulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGAco-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64 AE 06.01 nm and zeta-potential: +42.32 AE 02.70 mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01 AE1.19 mg of BSA per mg of NPs. The BSA adsorbed NPs (5 mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5 mg/ml, corresponding to a ratio of 1:1.5/NP:L-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae < 4.46 mm) of 70.67 AE 4.07% and mass median aerodynamic diameter (MMAD) of 2.80 AE 0.21 mm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76 AE 03.55% (A549 cell line) at 156.25 mg/ml concentration after 24 h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76 AE 1.54% relative esterolytic activity compared to standard BSA.2015 Published by Elsevier B.V.
Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted periods. Hence direct inhalation to the respiratory epithelium has been investigated extensively in the past decade, and seems to be an attractive approach to eradicate and hence overcome this widespread problem. Moreover, engineering inhalation formulations wherein the antibiotics are encapsulated within nanoscale carriers could serve to overcome many of the limitations faced by conventional antibiotics, like difficulty in treating intracellular pathogens such as mycobacteria spp. and salmonella spp., biofilmassociated pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, passage through the sputum associated with disorders like cystic fibrosis and chronic obstructive pulmonary disorder, systemic side effects following oral/parenteral delivery and inadequate concentrations of antibiotic at the site of infection leading to resistance. Encapsulation of antibiotics in nanocarriers may help in providing a protective environment to combat antibiotic degradation, confer controlled-release properties, hence reducing dosing frequency, and may increase uptake via specific and non-specific targeting modalities. Hence nanotechnology combined with direct administration to the airways using commercially available delivery devices, is a highly attractive formulation strategy to eradicate microorganisms from the lower respiratory tract, which might otherwise present opportunities for multi-drug resistance.
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