Investigating the Poverty-Reducing Effects of SNAP on Non-nutritional Family Outcomes: A Scoping Review.

INTRODUCTION/PURPOSE: Poverty-reduction efforts that seek to support households with children and enable healthy family functioning are vital to produce positive economic, health, developmental, and upward mobility outcomes. The Supplemental Nutrition Assistance Program (SNAP) is an effective poverty-reduction policy for individuals and families. This study investigated the non-nutritional effects that families experience when receiving SNAP benefits. METHODS: We conducted a scoping review using the PRISMA Guidelines and strategic search terms across seven databases from 01 January 2008 to 01 February 2023 (n=2456). Data extraction involved two researchers performing title-abstract reviews. Full-text articles were assessed for eligibility (n=103). Forty articles were included for data retrieval. RESULTS: SNAP positively impacts family health across the five categories of the Family Stress Model (Healthcare utilization for children and parents, Familial allocation of resources, Impact on child development and behavior, Mental health, and Abuse or neglect). DISCUSSION/CONCLUSION: SNAP is a highly effective program with growing evidence that it positively impacts family health and alleviates poverty. Four priority policy actions are discussed to overcome the unintentional barriers for SNAP: distributing benefits more than once a month; increasing SNAP benefits for recipients; softening the abrupt end of benefits when wages increase; and coordinating SNAP eligibility and enrollment with other programs.

Six years of progress in the oral biopharmaceutics area - A summary from the IMI OrBiTo project.

OrBiTo was a precompetitive collaboration focused on the development of the next generation of Oral Biopharmaceutics Tools. The consortium included world leading scientists from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with thirteen pharmaceutical companies. The goal of the OrBiTo project was to deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This goal was achieved through novel prospective investigations to define new methodologies or refinement of existing tools. Extensive validation has been performed of novel and existing biopharmaceutics tools using historical datasets supplied by industry partners as well as laboratory ring studies. A combination of high quality in vitro and in vivo characterizations of active drugs and formulations have been integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of gastrointestinal drug absorption and some of the best practices has been highlighted. This approach has given an unparalleled opportunity to deliver transformational change in European industrial research and development towards model based pharmaceutical product development in accordance with the vision of model-informed drug development.

In vivo models and decision trees for formulation development in early drug development: A review of current practices and recommendations for biopharmaceutical development.

The ability to predict new chemical entity performance using in vivo animal models has been under investigation for more than two decades. Pharmaceutical companies use their own strategies to make decisions on the most appropriate formulation starting early in development. In this paper the biopharmaceutical decision trees available in four EFPIA partners (Bayer, Boehringer Ingelheim, Bristol Meyers Squibb and Janssen) were discussed by 7 companies of which 4 had no decision tree currently defined. The strengths, weaknesses and opportunities for improvement are discussed for each decision tree. Both pharmacokineticists and preformulation scientists at the drug discovery & development interface responsible for lead optimization and candidate selection contributed to an overall picture of how formulation decisions are progressed. A small data set containing compound information from the database designed for the IMI funded OrBiTo project is examined for interrelationships between measured physicochemical, dissolution and relative bioavailability parameters. In vivo behavior of the drug substance and its formulation in First in human (FIH) studies cannot always be well predicted from in vitro and/or in silico tools alone at the time of selection of a new chemical entity (NCE). Early identification of the risks, challenges and strategies to prepare for formulations that provide sufficient preclinical exposure in animal toxicology studies and in FIH clinical trials is needed and represents an essential part of the IMI funded OrBiTo project. This article offers a perspective on the use of in vivo models and biopharmaceutical decision trees in the development of new oral drug products.

In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.

The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.

Near-point string: Simple method to demonstrate anticipated near point for multifocal and accommodating intraocular lenses.

UNLABELLED: We present a technique that uses a near-point string to demonstrate the anticipated near point of multifocal and accommodating intraocular lenses (IOLs). Beads are placed on the string at distances corresponding to the near points for diffractive and accommodating IOLs. The string is held up to the patient's eye to demonstrate where each of the IOLs is likely to provide the best near vision. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Use of the pentagastrin dog model to explore the food effects on formulations in early drug development.

The ability to extrapolate dosage performance from in vitro to in vivo situations has an important role in early drug development. In parallel, the Beagle dog has come to represent a useful animal model for extrapolation to humans especially when drugs formulated for humans are to be tested. In this article, the pentagastrin-induced Beagle dog model was validated internally to show that in the colony the dogs were generally responsive to known doses of pentagastrin that produces effects similar to gastrin in the stomach, i.e., increasing gastric acid production and lowering gastric pH. The effect was observed with a short time course, maximum pH lowering was observed between 0.5 and 1h with return to baseline at 2-4h. The dog stomach pH is a better representative of the human fasted stomach with this pretreatment. The ultimate goal was to use these animals in a food effect studies to predict the behavior of formulations in humans. The results for 4 compounds were provided in the dog and a clear relationship between the effect of food in the dog and the effect of food in humans was observed. While the directionality (positive or negative) of the effect could be adequately predicted, the extent of the effect could not be predicted for all the tested formulations of the 4 compounds. The data will be used to generate a database of known compounds from which a correlation can be drawn to make future predictions using the pentagastrin dog model.

Patients discharged with a prescription for acetaminophen-containing narcotic analgesics do not receive appropriate written instructions.

To determine whether patients given prescriptions for acetaminophen-containing narcotic analgesics receive appropriate discharge instructions to reduce their intake of or stop taking other acetaminophen-containing products, we evaluated discharge instructions given by an urban, tertiary-care emergency department from September 1 to September 18, 2001 to find patients discharged while taking narcotic-analgesic compounds containing acetaminophen. We evaluated these discharge instructions to determine whether they included instructions to reduce or discontinue the use of acetaminophen compounds. Among the 1,505 discharge instructions evaluated, we found that 108 patients were discharged with a narcotic-analgesic combination product containing acetaminophen. Of these 108 patients, none of those given a prescription for such an acetaminophen-containing product was instructed to reduce or discontinue the use of other acetaminophen products. Emergency physicians, during the specified study period, did not explain to their patients the need to reduce the use of other acetaminophen-containing products when prescribing acetaminophen-containing medications. Further inquiry into this potentially dangerous activity is warranted.

Validation of procedures for quantitative whole-body autoradiography using digital imaging.

The objective of this study was to demonstrate that tissue concentrations of radioactivity derived by digital analysis of autoradiograms were comparable to values derived from direct sampling and analysis of tissues. In addition, we describe the preparation and calibration of standards for use in quantitative whole-body autoradiography. For this study, three male Long-Evans hooded rats were administered 14C radioactivity intravenously. The animals were sectioned for whole-body autoradiography, with concomitant sampling of blood and 16 selected tissues. After 3 weeks of film exposure, the optical densities of the resulting autoradiograms were analyzed with a RAS3000 digital imaging system to estimate tissue concentrations of radioactivity. These concentrations were then compared with those obtained by direct analysis of the tissue samples. The concentrations derived from digital analysis of the autoradiograms were very highly correlated with those determined from direct tissue analysis (r = 0.956). Linear regression analysis yielded a straight line with a slope of 0.97 and a goodness of fit (r2) of 0.913. This analysis suggested that there is an approximate 1:1 correlation between concentration values determined by the two methods. Marked differences between the values derived via the two techniques were observed for only three tissues. However, this subset of the data accounted for only 6% of the total data, and the differences were probably due to contamination from adjacent tissues during excision. Overall, the concentrations of radioactivity derived from digital analysis of the autoradiograms were comparable to those derived from direct analysis of tissue samples. The results indicated that the digital analysis procedure for film can serve as a valuable adjunct to conventional tissue analysis for radioactivity.

Automated-extraction, high-performance liquid chromatographic method and pharmacokinetics in rats of a highly A2-selective adenosine agonist, CGS 21680.

CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N- ethylcarboxamidoadenosine, I) is a highly A2-selective (A2/A1 = 140), high-affinity adenosine agonist. A method has been devised to extract the compound from biological matrices with automated solid-phase extraction using C18 bonded silica columns. This is followed by reversed-phase, paired-ion chromatography on a Supelco LC-18-S column with fluorescence detection. The limit of quantitation is 5 ng/ml, but 1 ng/ml (five times the signal-to-noise ratio) can readily be detected. Tritium-labeled compound was used to study the pharmacokinetics in rats. After an intravenous dose of 0.3 mg/kg, biphasic elimination kinetics were observed for parent I, characterized by half-lives of 1.8 min (distribution) and 15 min (elimination). The volume of distribution in the terminal phase (V beta) was low (0.27 l/kg) and plasma clearance was moderate (0.83 l/kg/h). Although the compound was rapidly absorbed (mean Tmax = 13 min), low concentrations (mean Cmax = 94 ng/ml) were observed after an oral dose of 3.0 mg/kg, and bioavailability was only approximately 1.4%. Radioactivity persisted in plasma longer than parent compound after either dose, but levels were too low for isolation and structure identification of drug-derived compounds.

Physicochemical factors associated with binding and retention of compounds in ocular melanin of rats: correlations using data from whole-body autoradiography and molecular modeling for multiple linear regression analyses.

The relationship between the physicochemical characteristics of 27 new drug candidates and their distribution into the melanin-containing structure of the rat eye, the uveal tract, was examined. Tissue distribution data were obtained from whole-body autoradiograms of pigmented Long-Evans rats sacrificed at 5 min and 96 hr after dosing. The physicochemical parameters considered include molecular weight, pKa, degree of ionization, octanol/water partition coefficient (log Po/w), drug-melanin binding energy, and acid/base status of the functional groups within the molecule. Multiple linear regression analysis was used to describe the best model correlating physicochemical and/or biological characteristics of these compounds to their initial distribution at 5 min and to the retention of residual radioactivity in ocular melanin at 96 hr post-injection. The early distribution was a function primarily of acid/base status, pKa, binding energy, and log P(o/w), whereas uveal tract retention in rats was a function of volume of distribution (V1), log P(o/w), pKa, and binding energy. Further, there was a relationship between the initial distribution of a compound into the uveal tract and its retention 96 hr later. More specifically, the structures most likely to be distributed and ultimately retained at high concentrations were those containing strongly basic functionalities, such as piperidine or piperazine moieties and other amines. Further, the more lipophilic and, hence, widely distributed the basic compound, the greater the likelihood that it interacts with ocular melanin. In summary, the use of multiple linear regression analysis was useful in distinguishing which physicochemical characteristics of a compound or group of compounds contributed to melanin binding in pigmented rats in vivo.

Calculation of drug-melanin binding energy using molecular modeling.

Conformational analysis and molecular graphics are used to model a representative melanin structure to estimate a chemical's in vitro affinity for melanin. The modelling data fit to a simple linear equation relative to a logarithmic transformation of the experimentally-derived binding data (r = 0.901). The goodness of fit, as evidenced by the F-statistic, F (1,14) = 60.09 (p = 0.000002), for the regression indicates that this technique gives an accurate representation of the interaction of these chemicals with melanin in vitro.