Measuring adherence in a community-based elderly population.

OBJECTIVE: To examine the reliability and validity of the Medication Adherence Individual Review-Screening Tool (MedAdhIR-ST) for assessing medication adherence in a community-dwelling elderly population. DESIGN: A prospective, observational pilot study comparing the reliability and validity of the MedAdhIR-ST and the Medication Adherence Questionnaire (MAQ). SETTING: Independent senior-housing apartments and senior centers in Wake County, North Carolina. PARTICIPANTS: Eligible subjects included individuals 60 years of age or older who were living in the community and managing their own medication regimens. INTERVENTIONS: Each subject was asked to participate in two assessment visits, two weeks (+/- 3 days) apart, in which the questions of the MedAdhIR-ST and MAQ were administered. MAIN OUTCOME MEASURE: Medication adherence. RESULTS: Both tools showed moderate-to-high test/retest reliability in the study population (correlation coefficient of 0.632 for MAQ, and 0.699 for MedAdhIR-ST), and moderate internal consistency (Cronbach's a of 0.551 and 0.584, respectively). Moderate concordance in the ability to assess adherence was observed between MedAdhIR-ST and MAQ (positive correlation coefficient of 0.450). When compared with refill records, MedAdhIR-ST was slightly more sensitive (67% vs. 43%) and specific (60% vs. 50%) for detecting adherence and nonadherence, respectively, compared with MAQ. Exploratory factor analysis indicated that MedAdhIR-ST is multidimensional. CONCLUSION: MedAdhIR-ST appears to be a reliable and valid tool for screening nonadherence in a community-dwelling elderly population.

Medication errors and penalties in assisted living facilities.

OBJECTIVE: To determine the percentage of medication-related proposed penalties for licensed assisted living facilities in North Carolina. DESIGN: This retrospective, cross-sectional study examined all proposed penalties and related case-file narratives stemming from annual surveys of licensed assisted living facilities conducted by the state between July 2007 and December 2008. The percentage of medication-related deficiencies and proposed penalties were calculated. Associations between the medication-related proposed penalties and facility size, location, and penalty type were explored using chi-square tests. SETTING: Assisted living facilities in North Carolina. MAIN OUTCOME MEASURES: Percentage of medication- and non-medication-related penalties. RESULTS: A total of 1,256 licensed assisted living facilities (51% adult care homes, 59% metropolitan) were surveyed during the study period. There were 88 proposed penalties (51% medication-related) among 60 facilities. No association between medication-related proposed penalties and facility size or location was detected. However, an association (P = 0.002) was found between type of penalty (A or B) and whether the proposed penalty was medication- or non-medication-related (37.3% and 70.3% of Type A and B penalties, respectively, were medication related). Medications commonly cited were insulin, cardiovascular agents, supplements, anticonvulsants, and antipsychotics. Common categories of medication errors were drug not administered and wrong dose administered. CONCLUSIONS: Medication errors, regardless of facility size or location, were contributing factors in approximately one-half of violations sufficient enough to warrant a penalty proposal among the licensed assisted living facilities in North Carolina. These findings demonstrate a need for continued regulation and increased pharmacist involvement to improve medication safety.

Loss of the hSNF5 gene concomitantly inactivates p21CIP/WAF1 and p16INK4a activity associated with replicative senescence in A204 rhabdoid tumor cells.

hSNF5, the smallest member of the SWI/SNF chromatin remodeling complex, is lost in most malignant rhabdoid tumors (MRT). In MRT cell lines, reexpression of hSNF5 induces G1 cell cycle arrest, elevated p16INK4a, and activated replicative senescence markers, such as beta-galactosidase (beta-Gal) and plasminogen activator inhibitor-1. To compare the replicative senescence caused by hSNF5 in A204 cells to normal cellular senescence, we examined the activation of both p16INK4a and p21CIP/WAF1. Analogous to normal cellular senescence, both p16INK4a and p21CIP/WAF1 were up-regulated following hSNF5 restoration. Furthermore, we found that hSNF5 bound the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes. Using p16INK4a RNA interference, we showed its requirement for the replicative senescence caused by hSNF5 but not the growth arrest. Instead, p21CIP/WAF1 remained activated by hSNF5 in the absence of high p16INK4a expression, apparently causing the growth arrest in A204. Interestingly, we also found that, in the absence of p16INK4a, reexpression of hSNF5 also increased protein levels of a second cyclin-dependent kinase (CDK) inhibitor, p18INK4c. However, our data show that lack of hSNF5 does not abrogate cellular responsiveness to DNA damage or growth-inhibitory factors. In summary, our studies suggest that hSNF5 loss may influence the regulation of multiple CDK inhibitors involved in replicative senescence.

Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells.

The differentially expressed in adenocarcinoma of the lung (DAL-1) gene, which shares significant homology with members of the 4.1/ezrin/radixin/moesin/neurofibromatosis 2 (ERM/NF2) protein family, has previously been shown to suppress growth in lung cancer cell lines. This gene localizes to chromosome band 18p11.3, which undergoes loss of heterozygosity (LOH) in nonsmall cell lung carcinomas and a significant proportion of ductal carcinomas in situ (DCIS) of the breast. This finding suggests that alteration of gene(s) (possibly DAL-1) within this chromosomal region may be important early in the progression of breast disease. We generated MCF-7 cell lines expressing DAL-1 constitutively or under the control of an inducible promoter and analyzed the effect of DAL-1 expression on growth. These investigations revealed that the DAL-1 protein suppresses the growth of MCF-7 cells and may do so in part through the induction of apoptosis. In addition, expression of DAL-1 increased attachment of these cells to a variety of extracellular matrices. This is the first evidence that the DAL-1 protein functions at the interface between cell adhesion and apoptosis in controlling cell growth.