ABSTRACT
BACKGROUND: Innovative digital technology systems that support and monitor real-time medication intake are now available commercially; however, there is limited knowledge of the use of such technology in patients' homes. One such smart medication dispenser, spencer, provides alerts to patients to take their medications and allows for tracking and reporting real-time medication adherence data. OBJECTIVE: The objectives of this study were to examine the use of a smart medication dispenser as a medication adherence and self-management support tool for community dwelling adults over a 6-month period, in addition to usability, usefulness, satisfaction, and impact on caregiver support. METHODS: This prospective, observational study invited community-dwelling adults aged 45 years and older taking at least one chronic medication and their caregivers to use this smart medication dispenser for their medication administration for 6 months. Adherence was defined as a dose intake within 2 hours post scheduled time. Real-time adherence data were collected using the smart medication dispenser and the AdhereNet platform. Usability, usefulness, and satisfaction were measured using the System Usability Scale and the Usefulness, Satisfaction, and Ease of Use questionnaire, respectively. Caregiver burden was measured on a visual analog scale at baseline and at the end of the 6-month study period. RESULTS: A total of 58 participants were recruited, of which 55% (32/58) were female with a mean age of 66.36 (SD 11.28; range 48-90) years. Eleven caregiver participants were recruited, of whom 91% (10/11) were female. The average monthly adherence over 6 months was 98% (SD 3.1%; range 76.5%-100%). The average System Usability score was 85.74 (n=47; SD 12.7; range 47.5-100). Of the 46 participants who provided data, 44 (96%) rated the product as easy, 43 (93%) as simple to use, and 43 (93%) were satisfied with the product. Caregiver burden prior to and following smart medication dispenser use for 6 months was found to be statistically significantly different (P<.001; CI 2.11-5.98). CONCLUSIONS: Smart medication adherence products such as spencer, when connected and clinically monitored, can be a useful solution for medication management and have the potential to improve caregiver burden.
ABSTRACT
The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1- and MED1-mediated transcription. MED1 expression levels in K562 erythroleukemia cells paralleled the levels of GATA1-targeted gene transcription and erythroid differentiation. An N-terminal fragment of MED1, MED1(1-602), which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation, and introduction of MED1(1-602) into Med1(-/-) mouse embryonic fibroblasts (MEFs) partially rescued GATA1-mediated transcription. The C-terminal zinc-finger domain of GATA1 interacts with the MED1(1-602)-interacting coactivator CCAR1, CoCoA and MED1(681-715). CCAR1 and CoCoA synergistically enhanced GATA1-mediated transcription from the γ-globin promoter in MEFs. Recombinant GATA1, CCAR1, CoCoA and MED1(1-602) formed a complex in vitro, and GATA1, CCAR1, CoCoA and MED1 were recruited to the γ-globin promoter in K562 cells during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1-MED1 axis may help to fine-tune GATA1 function during GATA1-mediated homeostasis events.
Subject(s)
Apoptosis Regulatory Proteins/metabolism , Calcium-Binding Proteins/metabolism , Cell Cycle Proteins/metabolism , GATA1 Transcription Factor/metabolism , Mediator Complex Subunit 1/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Calcium-Binding Proteins/genetics , Cell Cycle Proteins/genetics , Cell Differentiation/genetics , Cells, Cultured , Female , GATA1 Transcription Factor/genetics , Humans , K562 Cells , Male , Mediator Complex Subunit 1/genetics , Mice , Mice, Inbred C57BL , Promoter Regions, Genetic , Transcription Factors , Transcription, Genetic , Transcriptional Activation , gamma-Globins/geneticsABSTRACT
The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor ß (TRß) on the TSHß gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHß gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHß gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHß gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHß gene promoter.
