Gender Equality, Drinking Cultures and Second-Hand Harms from Alcohol in the 50 US States.

BackgroundGender inequality and cultures of binge drinking may increase the risk of second-hand harms from alcohol.MethodsUsing the 2014-2015 National Alcohol Survey and 2015 National Alcohol's Harm to Others Survey (N = 7792), we examine associations of state-level gender equality measures (contraceptive access, abortion rights, women's economic equality) and binge drinking cultures (rates of men's and women's binge drinking) with individual-level indicators of second-hand harms by drinking strangers and partners/spouses.ResultsIn main effects models, only male binge drinking was associated with greater odds of harms from drinking strangers. There were significant interactions of gender equality with male binge drinking: High male binge drinking rates were more strongly associated with stranger-perpetrated harms in states low on contraceptive access or abortion rights compared to states high on these measures. Conversely, male binge drinking was more strongly associated with spouse/partner-perpetrated second-hand harms in states with more economic equality, compared to states lower on this measure.ConclusionsDetrimental effects of high male binge drinking rates may be modified by gender equality. Targeted interventions may reduce alcohol-related harms experienced by women in states with high rates of male binge drinking. Restrictions in access to contraception and abortion may exacerbate harms due to men's drinking

Integrated Approaches to Identify and Predict Pharmacokinetic-Based Dietary Substance-Drug Interactions

The large variation in bioactive ingredient composition inherent to natural products, including dietary substances, can confound the design and interpretation of natural product-drug interaction studies. The purpose of this dissertation was to address this overlooked issue by developing a framework to evaluate pharmacokinetic-based dietary substance-drug interactions such that ultimately, firm clinical recommendations can be made. Fruit juices represent a diverse market of popular foods containing phytochemicals that can inhibit drug metabolizing enzymes and transporters in the intestine. The potential increase or decrease in systemic drug exposure could lead to adverse effects or therapeutic failure, respectively. A multi-experimental approach utilizing in vitro (bioactivity-guided fractionation), in vivo (clinical study), and in silico (modeling and simulation) methods was applied to the exemplar dietary substance grapefruit juice (GFJ). GFJ has been shown to inhibit oral absorption of certain drugs that require the uptake transporter family of organic anion transporting polypeptides (OATPs) located in the intestine. The inhibitory effects of GFJ and a unique food-grade GFJ devoid of two classes of candidate OATP inhibitors, furanocoumarins and polymethoxyflavones, on intestinal OATP activity were evaluated in OATP1A2- and OATP2B1-transfected cells and in healthy volunteers. Results from the in vitro study were predictive of the in vivo study, demonstrating that furanocoumarins and polymethoxyflavones do not contribute to intestinal OATP inhibition. Bioactivity-guided fractionation of GFJ using estrone 3-sulfate as a probe substrate and OATP2B1-transfected cells yielded several potent groups of OATP2B1 inhibitors. GFJ also has been shown to inhibit the metabolism of drugs that require the cytochrome P450 3A4 (CYP3A4) enzyme in the intestine. A population-based modeling and simulation program incorporating in vitro and in vivo data from the literature evaluated two furanocoumarins, 6',7'-dihydroxybergamottin and bergamottin, as candidate marker compounds predictive of the GFJ effect on select CYP3A4 drug substrates. Results from the in silico study supported both furanocoumarins as potential marker compounds. These integrated approaches address the challenges of, and begin to establish best practices for, the study of dietary substance-drug interactions. Such research methods must be refined and reinforced as concomitant intake of new (and older) natural products and drugs continues to rise.Doctor of Philosoph

Internet Use for Health Information among American Indians: Facilitators and Inhibitors

Our research team explored Internet use among a heterogeneous American Indian (AI) population to determine Internet use in relation to health information seeking behaviors. Participants examined an AI culturally-tailored tobacco website as an example to explain what they wanted in an AI Internet health site. Using community-based participatory research, we conducted 10 focus groups with non-college AI men and women (N=96), stratified by age (18-29, 30-49, and 50 and over) to better understand their perceptions of Internet use and health information needs. We found that Internet use varied greatly among all strata. Participants referenced WebMD© more than any other website, but participants were not pleased with the design and navigation. When examining the sample website, participants across strata stressed that recreational and traditional tobacco use should be discussed. Participants in all strata desired a simple website design with easy to read text accompanied by images. In order to gain and maintain cultural respect, participants stated that web designers should be aware that some images hold cultural meaning, particularly tobacco. Baseline data are needed for AI’s use of the Internet to obtain health information; this research is helpful to address health inequalities among AI, particularly access to web-based health information

Development of a Bamlanivimab Infusion Process in the Emergency Department for Outpatient COVID-19 Patients

The coronavirus disease 2019 (COVID-19) pandemic has prompted the creation of new therapies to help fight against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Bamlanivimab is a SARS-CoV-2 monoclonal antibody that is administered as an intravenous infusion to ambulatory patients with mild or moderate COVID-19, but a concern that arose was deciding the optimal location for patients to receive the medication. This report describes the development and implementation of a bamlanivimab infusion center in the emergency department of three hospitals in Orange County, California, shortly after bamlanivimab received emergency use authorization. As a result, a total of 601 patients received bamlanivimab in one of these three emergency departments between December 2020 to April 2021. The emergency department was shown to be an optimal setting for administration of bamlanivimab due to its convenience, accessibility, and capabilities for monitoring patients

Barriers to colorectal cancer screening among American Indian men aged 50 or older, Kansas and Missouri, 2006-2008

American Indian (AI) men have some of the highest rates of colorectal cancer (CRC) in the United States but among the lowest screening rates. Our goal was to better understand awareness and discourse about colorectal cancer in a heterogeneous group of AI men in the Midwestern United States. Focus groups were conducted with AI men (N = 29); data were analyzed using a community-participatory approach to qualitative text analysis. Several themes were identified regarding knowledge, knowledge sources, and barriers to and facilitators of screening. Men in the study felt that awareness about colorectal cancer was low, and people were interested in learning more. Education strategies need to be culturally relevant and specific

Evaluation of the Effects of Repeat-Dose Dabrafenib on the Single-Dose Pharmacokinetics of Rosuvastatin (OATP1B1/1B3 Substrate) and Midazolam (CYP3A4 Substrate)

Dabrafenib; Drug interaction; PharmacokineticsDabrafenib; Interacción de fármacos; FarmacocinéticaDabrafenib; Interacció de fàrmacs; FarmacocinèticaDabrafenib is an oral BRAF kinase inhibitor approved for the treatment of various BRAF V600 mutation–positive solid tumors. In vitro observations suggesting cytochrome P450 (CYP) 3A induction and organic anion transporting polypeptide (OATP) inhibition prompted us to evaluate the effect of dabrafenib 150 mg twice daily on the pharmacokinetics of midazolam 3 mg (CYP3A substrate) and rosuvastatin 10 mg (OATP1B1/1B3 substrate) in a clinical phase 1, open-label, fixed-sequence study in patients with BRAF V600 mutation–positive tumors. Repeat dabrafenib dosing resulted in a 2.56-fold increase in rosuvastatin maximum observed concentration (Cmax), an earlier time to Cmax, but only a 7% increase in area under the concentration-time curve from time 0 (predose) extrapolated to infinite time. Midazolam Cmax and AUC extrapolated to infinite time decreased by 47% and 65%, respectively, with little effect on time to Cmax. No new safety findings were reported. Exposure of drugs that are CYP3A4 substrates is likely to decrease when coadministered with dabrafenib. Concentrations of medicinal products that are sensitive OATP1B1/1B3 substrates may increase during the absorption phase.This study was sponsored by GlaxoSmithKline; dabrafenib and trametinib are assets of Novartis AG as of March 2, 2015

Influence of Dietary Substances on Intestinal Drug Metabolism and Transport

Successful delivery of promising new chemical entities via the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often overlooked, effect of dietary substances on drug disposition and response. Some dietary substances, particularly fruit juices, have been shown to inhibit biochemical processes in the intestine, leading to altered pharmacokinetic (PK), and potentially pharmacodynamic (PD), outcomes. Inhibition of intestinal CYP3A-mediated metabolism is the major mechanism by which fruit juices, including grapefruit juice, enhances systemic exposure to new and already marketed drugs. Inhibition of intestinal non-CYP3A enzymes and apically-located transport proteins represent recently identified mechanisms that can alter PK and PD. Several fruit juices have been shown to inhibit these processes in vitro, but some interactions have not translated to the clinic. The lack of in vitro-in vivo concordance is due largely to a lack of rigorous methods to elucidate causative ingredients prior to clinical testing. Identification of specific components and underlying mechanisms is challenging, as dietary substances frequently contain multiple, often unknown, bioactive ingredients that vary in composition and bioactivity. A translational research approach, combining expertise from clinical pharmacologists and natural products chemists, is needed to develop robust models describing PK/PD relationships between a given dietary substance and drug of interest. Validation of these models through well-designed clinical trials would facilitate development of common practice guidelines for managing drug-dietary substance interactions appropriately

Highly Potent 1H-1,2,3-Triazole-Tethered Isatin-Metronidazole Conjugates Against Anaerobic Foodborne, Waterborne, and Sexually-Transmitted Protozoal Parasites

Parasitic infections like amebiasis, trichomoniasis, and giardiasis are major health threats in tropical and subtropical regions of the world. Metronidazole (MTZ) is the current drug of choice for amebiasis, giardiasis, and trichomoniasis but it has several adverse effects and potential resistance is a concern. In order to develop alternative antimicrobials, a library of 1H-1,2,3-triazole-tethered metronidazole-isatin conjugates was synthesized using Huisgen\u27s azide-alkyne cycloaddition reaction and evaluated for their amebicidal, anti-trichomonal, and anti-giardial potential. Most of the synthesized conjugates exhibited activities against Trichomonas vaginalis, Tritrichomonas foetus, Entamoeba histolytica, and Giardia lamblia. While activities against T. vaginalis and T. foetus were comparable to that of the standard drug MTZ, better activities were observed against E. histolytica and G. lamblia. Conjugates 9d and 10a were found to be 2–3-folds more potent than MTZ against E. histolytica and 8–16-folds more potent than MTZ against G. lamblia. Further analysis of these compounds on fungi and bacteria did not show inhibitory activity, demonstrating their specific anti-protozoal properties

Ensuring Healthy American Indian Generations for Tomorrow through Safe and Healthy Indoor Environments

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.American Indians (AI) have the highest rate of severe physical housing problems in the U.S. (3.9%). Little information exists about the environmental hazards in AI homes. The purposes of this paper are to discuss challenges that were encountered when recruiting AI for a home-and employment-based environmental health assessments, highlight major successes, and propose recommendations for future indoor environmental health studies. The Center for American Indian Community Health (CAICH) and Children’s Mercy Hospital’s Center for Environmental Health and Allergy and Immunology Research Lab collaborated to provide educational sessions and healthy home assessments for AI. Through educational trainings, more than 240 AI were trained on the primary causes of health problems in homes. A total of 72 homes and places of employment were assessed by AI environmental health specialists. The top three categories with the most concerns observed in the homes/places of employment were allergens/dust (98%), safety/injury (89%) and chemical exposure (82%). While some information on smoking inside the home was collected, these numbers may have been underreported due to stigma. This was CAICH’s first endeavor in environmental health and although challenges arose, many more successes were achieved