ABSTRACT
OBJECTIVES: To test the effect of "Talking Pill Bottles" on medication self-efficacy, knowledge, adherence, and blood pressure readings among hypertensive patients with low health literacy and to assess patients' acceptance of this innovation. DESIGN: Longitudinal nonblinded randomized trial with standard treatment and intervention arms. SETTING AND PARTICIPANTS: Two community pharmacies serving an ethnically diverse population in the Pacific Northwest. Participants were consented patients with antihypertension prescriptions who screened positive for low health literacy based on the Test of Functional Health Literacy Short Form. Participants in the intervention arm received antihypertensive medications and recordings of pharmacists' counseling in Talking Pill Bottles at baseline. Control arm participants received antihypertensive medications and usual care instructions. MAIN OUTCOME MEASURES: Comparison and score changes between baseline and day 90 for medication knowledge test, Self-Efficacy for Appropriate Medication Use Scale (SEAMS), Morisky Medication Adherence Scale (MMAS-8), blood pressure, and responses to semistructured exit interviews and Technology Acceptance Model surveys. RESULTS: Of 871 patients screened for health literacy, 134 eligible participants were enrolled in the trial. The sample was elderly, ethnically diverse, of low income, and experienced regarding hypertension and medication history. In both arms, we found high baseline scores in medication knowledge test, SEAMS, and MMAS-8 and minimal changes in these measures over the 90-day study period. Blood pressure decreased significantly in the intervention arm. Acceptability scores for the Talking Pill Bottle technology were high. CONCLUSION: Our results suggest that providing audio-assisted medication instructions in Talking Pill Bottles positively affected blood pressure control and was well accepted by patients with low health literacy. Further research involving newly diagnosed patients is needed to mitigate possible ceiling effects that we observed in an experienced population.
Subject(s)
Antihypertensive Agents/administration & dosage , Health Knowledge, Attitudes, Practice , Health Literacy , Hypertension/drug therapy , Patient Education as Topic/methods , Aged , Aged, 80 and over , Blood Pressure/drug effects , Community Pharmacy Services/organization & administration , Counseling/methods , Female , Humans , Longitudinal Studies , Male , Medication Adherence , Middle Aged , Patient Acceptance of Health Care , Pharmacists/organization & administration , Pilot Projects , Professional Role , Self EfficacyABSTRACT
Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models.
Subject(s)
Drug Design , Indoles/chemical synthesis , Piperidines/chemical synthesis , Protein Kinase Inhibitors/chemical synthesis , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Animals , Binding Sites , Cell Line, Tumor , Crystallography, X-Ray , Cytochrome P-450 CYP3A/metabolism , Female , Half-Life , Humans , Indoles/pharmacokinetics , Indoles/therapeutic use , Lung/drug effects , Lung/metabolism , Mice , Neoplasms/drug therapy , Piperidines/pharmacokinetics , Piperidines/therapeutic use , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/therapeutic use , Protein Structure, Tertiary , Rats , Receptor Protein-Tyrosine Kinases/metabolism , Structure-Activity Relationship , Transplantation, HeterologousABSTRACT
The 70-kDa ribosomal protein S6 kinase (p70S6K) is part of the PI3K/AKT/mTOR pathway and has been implicated in cancer. High throughput screening versus p70S6K led to the identification of aminopyrimidine 3a as active inhibitor. Lead optimization of 3a resulted in highly potent, selective, and orally bioavailable pyrazolopyrimidines. In this manuscript we report the structure-activity relationship of this series and pharmacokinetic, pharmacodynamic, and efficacy data of the lead compound 13c.
Subject(s)
Antineoplastic Agents/chemical synthesis , Protein Kinase Inhibitors/chemical synthesis , Pyrazoles/chemical synthesis , Pyrimidines/chemical synthesis , Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors , Administration, Oral , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Biological Availability , Cell Line, Tumor , Drug Design , High-Throughput Screening Assays , Humans , Inhibitory Concentration 50 , Male , Mice , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/pharmacology , Pyrazoles/pharmacokinetics , Pyrazoles/pharmacology , Pyrimidines/pharmacokinetics , Pyrimidines/pharmacology , Rats , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Signal Transduction , Solubility , Structure-Activity Relationship , Xenograft Model Antitumor AssaysABSTRACT
Activation of the PI3K/Akt/mTOR kinase pathway is frequently associated with human cancer. Selective inhibition of p70S6Kinase, which is the last kinase in the PI3K pathway, is not sufficient for strong tumor growth inhibition and can lead to activation of upstream proteins including Akt through relief of a negative feedback loop. Targeting multiple sites in the PI3K pathway might be beneficial for optimal activity. In this manuscript we report the design of dual Akt/p70S6K inhibitors and the evaluation of the lead compound 11b in vivo, which was eventually advanced into clinical development.
Subject(s)
Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors , Animals , Dogs , Enzyme Activation/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Haplorhini , Humans , Mice , Microsomes/drug effects , Models, Molecular , Molecular Structure , Phosphatidylinositol 3-Kinases/drug effects , Pyrazoles/chemistry , Pyridines/chemistryABSTRACT
BACKGROUND: Pictographs (or pictograms) have been widely utilized to convey medication related messages and to address nonadherence among patients with low health literacy. Yet, patients do not always interpret the intended messages on commonly used pictographs correctly and there are questions how they may be delivered on mobile devices. OBJECTIVE: Our objectives are to refine a set of pictographs to use as medication reminders and to establish preliminary steps for delivery via smart phones. METHODS: Card sorting was used to identify existing pictographs that focus group members found "not easy" to understand. Participants then explored improvements to these pictographs while iterations were sketched in real-time by a graphic artist. Feedback was also solicited on how selected pictographs might be delivered via smart phones in a sequential reminder message. The study was conducted at a community learning center that provides literacy services to underserved populations in Seattle, WA. Participants aged 18 years and older who met the criteria for low health literacy using S-TOFHLA were recruited. RESULTS: Among the 45 participants screened for health literacy, 29 were eligible and consented to participate. Across four focus group sessions, participants examined 91 commonly used pictographs, 20 of these were ultimately refined to improve comprehensibility using participatory design approaches. All participants in the fifth focus group owned and used cell phones and provided feedback on preferred sequencing of pictographs to represent medication messages. CONCLUSION: Low literacy adults found a substantial number of common medication label pictographs difficult to understand. Participative design processes helped generate new pictographs, as well as feedback on the sequencing of messages on cell phones, that may be evaluated in future research.
ABSTRACT
Background: Pictographs (or pictograms) have been widely utilized to convey medication related messages and to address nonadherence among patients with low health literacy. Yet, patients do not always interpret the intended messages on commonly used pictographs correctly and there are questions how they may be delivered on mobile devices. Objective: Our objectives are to refine a set of pictographs to use as medication reminders and to establish preliminary steps for delivery via smart phones. Methods: Card sorting was used to identify existing pictographs that focus group members found «not easy» to understand. Participants then explored improvements to these pictographs while iterations were sketched in real-time by a graphic artist. Feedback was also solicited on how selected pictographs might be delivered via smart phones in a sequential reminder message. The study was conducted at a community learning center that provides literacy services to underserved populations in Seattle, WA. Participants aged 18 years and older who met the criteria for low health literacy using S-TOFHLA were recruited. Results: Among the 45 participants screened for health literacy, 29 were eligible and consented to participate. Across four focus group sessions, participants examined 91 commonly used pictographs, 20 of these were ultimately refined to improve comprehensibility using participatory design approaches. All participants in the fifth focus group owned and used cell phones and provided feedback on preferred sequencing of pictographs to represent medication messages. Conclusion: Low literacy adults found a substantial number of common medication label pictographs difficult to understand. Participative design processes helped generate new pictographs, as well as feedback on the sequencing of messages on cell (AU)
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