The Medication Regimen of Patients With Heart Failure: The Gerontologic Considerations and Anticholinergic Burden: A Mixed-Methods Study.

BACKGROUND: Although prescription medication adherence has been studied in the population living with heart failure (HF), little attention has focused on the patient's overall medication practices including over-the-counter medications. Patients with HF live with the certainty that their quality of life depends on the proper management of multiple medications. Failure to properly manage prescription medications increases the risk of exacerbation of HF and increased rates of rehospitalization. OBJECTIVES: The aim of the quantitative component of this study was to identify medication practices in patients with HF. The aim of the qualitative component was to identify themes of patients with high and low HF medication self-efficacy. METHODS: A convergent parallel mixed-methods design was followed. Quantitative interviews were conducted by telephone with 41 patients living with HF around their medication-taking and lifestyle behaviors. Immediately thereafter, qualitative interviews were conducted to elicit the patient's perspective of their therapeutic regimen. RESULTS: Patients are prescribed medications not recommended for the gerontologic population and/or risk anticholinergic burden. Although highly confident, patients admit to a plethora of errors. CONCLUSION: Future study is required to ensure safe transitions to home and enhance technology to provide seamless communication between patients and providers.

Concurrent use of amphetamine stimulants and antidepressants by undergraduate students.

Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Significant differences were found between students reporting (n=79; 4.0%) and not reporting (n=1,897; 96%) amphetamine-stimulant use in the past month - in terms of race/ethnicity, class standing, residence, health symptoms, self-health report - in addition to alcohol, tobacco, pain-reliever, and antidepressant use. Health symptoms reported more often by stimulant users included depression, diarrhea, difficulty sleeping, fatigue, dizziness, difficulty concentrating, and nicotine craving. Health care providers of college students should query these patients about symptoms that could be related to depression and amphetamine use. In particular, they should provide education at the point of care around the risks of amphetamine use in general and the specific risks in those students who have symptoms of depression and/or are taking antidepressant medication. Prevention programs should also target the risks of concurrent use of amphetamines, antidepressants, and other drugs among college students.

Promoting safe and effective use of OTC medications: CHPA-GSA National Summit.

Research on the ways older people use prescription medications (Rx) is a mainstay of the gerontological literature because use of Rx medications is common, and appropriate use is central to effective management of chronic disease. But older adults are also major consumers of over-the-counter (OTC) medications, which can be equally significant for self-care. Nearly half of older adults aged 75-85, for example, are regular users of an OTC product. Ensuring that consumers safely and effectively use OTC products is critical in order to minimize potential drug-drug interactions and unintentional misuse. Yet we know surprisingly little about the ways older adults select OTC medications and decide when to start or stop use, how older people actually take these medications, or how involved clinicians and family members are in older adult OTC behavior. Research in this area is critical for developing interventions to help ensure safe and appropriate OTC use. For this reason, The Gerontological Society of America (GSA), in partnership with the Consumer Healthcare Products Association (CHPA), convened a summit of experts to set an agenda for research in OTC behaviors among older adults. The panel suggested a need for research in 5 key areas: Health literacy and OTC behavior, decision making and OTC use, the role of clinicians in OTC medication behavior, older adult OTC behavior and family care, and technologies to promote optimal use of OTC medications.

Reducing Adverse Self-Medication Behaviors in Older Adults with Hypertension: Results of an e-health Clinical Efficacy Trial.

A randomized controlled efficacy trial targeting older adults with hypertension (age 60 and over) provided an e-health, tailored intervention with the "next generation" of the Personal Education Program (PEP-NG). Eleven primary care practices with advanced practice registered nurse (APRN) providers participated. Participants (N = 160) were randomly assigned by the PEP-NG (accessed via a wireless touchscreen tablet computer) to either control (entailing data collection and four routine APRN visits) or tailored intervention (involving PEP-NG intervention and four focused APRN visits) group. Compared to patients in the control group, patients receiving the PEP-NG e-health intervention achieved significant increases in both self-medication knowledge and self-efficacy measures, with large effect sizes. Among patients not at BP targets upon entry to the study, therapy intensification in controls (increased antihypertensive dose and/or an additional antihypertensive) was significant (p = .001) with an odds ratio of 21.27 in the control compared to the intervention group. Among patients not at BP targets on visit 1, there was a significant declining linear trend in proportion of the intervention group taking NSAIDs 21-31 days/month (p = 0.008). Satisfaction with the PEP-NG and the APRN provider relationship was high in both groups. These results suggest that the PEP-NG e-health intervention in primary care practices is effective in increasing knowledge and self-efficacy, as well as improving behavior regarding adverse self-medication practices among older adults with hypertension.

Psychometrics of the computer-based Relationships with Health Care Provider Scale in older adults.

The type and quality of the provider-patient health care relationship impacts patient adherence. The study purpose was to convert the 5-item paper and pencil Relationships With Health Care Provider Scale (RHCPS) to a reliable and valid computer-based scale for use with older adults. Outpatient adults (N = 121) older than 59 years were recruited. The RHCPS underwent several iterations documenting internal consistency reliability, content and factorial validity, and scale usability in a computer tablet format. A total of 5 expert judges rated all 5 items as valid, which resulted in a scale content validity index of 1. Cronbach's standardized alpha was .81. Principal components analysis extracted 1 factor (eigenvalue > 1; confirmed by scree plot) as anticipated. Computer-based RHCPS has the potential to reveal valuable clinical and scientific data on patient-provider relationships among older adults.

A Qualitative Study of Older Adults and Computer Use for Health Education: "It opens people's eyes"

Adults over the age of 60 struggle with achieving target blood pressure readings due to difficulties seeing, hearing and understanding medical information which can result in poor adherence and drug interactions that can be fatal. According to the Institute of Medicine (2000) approximately 10% of adverse drug events may be attributed to communication failure between the provider and patient. Informing patients of potential drug interactions with over-the-counter (OTC) medications, supplements and alcohol use can contribute to better blood pressure control. The Next Generation Personal Education Program (PEP-NG) was designed to improve patient care by educating both older adults and their providers about the dangers of adverse drug interactions arising from self-medication. This web based program analyzes information entered by the patient user (with a stylus on a tablet computer) and delivers tailored interactive educational content applicable to the user's reported medication behaviors. This qualitative study demonstrated that even amongst participants that may not feel computer literate (older-age generation) it can be a useful tool for information dissemination and also a successful way to improve communication between provider and patient.

Advanced practice registered nurse usability testing of a tailored computer-mediated health communication program.

This study tested the usability of a touch-screen-enabled Personal Education Program with advanced practice RNs. The Personal Education Program is designed to enhance medication adherence and reduce adverse self-medication behaviors in older adults with hypertension. An iterative research process was used, which involved the use of (1) pretrial focus groups to guide the design of system information architecture, (2) two different cycles of think-aloud trials to test the software interface, and (3) post-trial focus groups to gather feedback on the think-aloud studies. Results from this iterative usability-testing process were used to systematically modify and improve the three Personal Education Program prototype versions-the pilot, prototype 1, and prototype 2. Findings contrasting the two separate think-aloud trials showed that APRN users rated the Personal Education Program system usability, system information, and system-use satisfaction at a moderately high level between trials. In addition, errors using the interface were reduced by 76%, and the interface time was reduced by 18.5% between the two trials. The usability-testing processes used in this study ensured an interface design adapted to APRNs' needs and preferences to allow them to effectively use the computer-mediated health-communication technology in a clinical setting.

Reducing adverse self-medication behaviors in older adults with the Next Generation Personal Education Program (PEP-NG): Design and methodology.

A randomized controlled efficacy trial targeting older adults with hypertension is providing a tailored education intervention with a Next Generation Personal Education Program (PEP-NG) in primary care practices in New England. Ten participating advanced practice registered nurses (APRNs) completed online knowledge and self-efficacy measures pre-onsite training and twice more after completing a continuing education program. Patient participants self-refer in response to study recruitment brochures and posters. Twenty-four participants from each APRN practice (total N = 240) are randomly assigned by the PEP-NG software to either control (data collection and four routine APRN visits) or tailored intervention (PEP-NG interface and four focused APRN visits) conditions. Patients access the PEP-NG interface via wireless tablet and use a stylus to answer demographic, knowledge, and self-efficacy questions as well as prescription and over-the-counter self-medication practice questions. The PEP-NG analyzes patient-reported information and delivers tailored educational content. Patients' outcome measures are self-reported antihypertensive medication adherence, blood pressure, knowledge and self-efficacy concerning potential adverse self-medication practices, adverse self-medication behavior "risk" score and satisfaction with the PEP-NG and APRN provider relationship. APRN outcome measures are knowledge and self-efficacy concerning adverse self-medication practices, self-efficacy for communicating with older adults and satisfaction with the PEP-NG. Time-motion and cost-benefit analyses will be conducted.

A pilot program at the worksite to reduce adverse self-medication behaviors.

A Next Generation Personal Education Program (PEP-NG) that captures self-reported medication behaviors and delivers a tailored educational intervention on a touchscreen interface was piloted with 11 adults with hypertension, aged 45-60 years, in a worksite setting. A time series design with multiple institution of treatment (four visits over three months) was employed. Blood pressure (BP), self-medication behaviors, self-efficacy, and knowledge for avoiding adverse self-medication behaviors were assessed at each of four visits. Satisfaction was assessed once at visit 4. Measures pre-PEP (visit 1) to visit 4 were compared with paired t-tests. The adverse self-medication behavior risk score decreased significantly from visit 1 to visit 4 (p < 0.05) with a medium effect size. Both knowledge and self-efficacy for avoiding adverse self-medication behaviors increased significantly (p < 0.05) with large effect sizes. All six participants not at BP goal (<140/90 mmHg) on visit 1 were at goal by visit 4. User satisfaction was high as assessed by both quantitative measures and qualitative interviews. These positive results suggest the PEP could play a central role in worksite wellness programs aimed at workers with hypertension.

Usability testing by older adults of a computer-mediated health communication program.

Failure to adhere to an antihypertensive regimen and interactions between antihypertensives and other medicines represent serious health threats to older adults. This study tested the usability of a touch-screen-enabled personal education program (PEP). Findings showed that older adults rated the PEP system usability, system usefulness, and system-use satisfaction at a moderately high level for prototype-1 and at an exceptionally high level for prototype-2. A 201.91% reduction in interface errors and a 31.08% decrease in interface time also were found between the two trials. This participatory usability design was highly successful in tailoring its program interface design to accommodate older users to enhance their health communication and technology use efficacy.

The influence of genetic polymorphisms on population variability in six xenobiotic-metabolizing enzymes.

This review provides variability statistics for polymorphic enzymes that are involved in the metabolism of xenobiotics. Six enzymes were evaluated: cytochrome P-450 (CYP) 2D6, CYP2E1, aldehyde dehydrogenase-2 (ALDH2), paraoxonase (PON1), glutathione transferases (GSTM1, GSTT1, and GSTP1), and N-acetyltransferases (NAT1 and NAT2). The polymorphisms were characterized with respect to (1) number and type of variants, (2) effects of polymorphisms on enzyme function, and (3) frequency of genotypes within specified human populations. This information was incorporated into Monte Carlo simulations to predict the population distribution and describe interindividual variability in enzyme activity. The results were assessed in terms of (1) role of these enzymes in toxicant activation and clearance, (2) molecular epidemiology evidence of health risk, and (3) comparing enzyme variability to that commonly assumed for pharmacokinetics. Overall, the Monte Carlo simulations indicated a large degree of interindividual variability in enzyme function, in some cases characterized by multimodal distributions. This study illustrates that polymorphic metabolizing systems are potentially important sources of pharmacokinetic variability, but there are a number of other factors including blood flow to liver and compensating pathways for clearance that affect how a specific polymorphism will alter internal dose and toxicity. This is best evaluated with the aid of physiologically based pharmacokinetic (PBPK) modeling. The population distribution of enzyme activity presented in this series of articles serves as inputs to such PBPK modeling analyses.

Genetic polymorphism in cytochrome P450 2D6 (CYP2D6): Population distribution of CYP2D6 activity.

Cytochrome P-450 2D6 (CYP2D6) is involved in the metabolism of many therapeutic drugs even though the enzyme represents a small proportion of the total CYP content of human liver. In vivo phenotyping with probe drug substrates such as debrisoquine and dextromethorphan showed a clear separation between poor metabolizers (PM) and extensive metabolizers (EM). This polymorphism may affect susceptibility to environmental disease, as suggested by molecular epidemiologic studies that found an association between CYP2D6 metabolizer phenotype and cancer risk; however, this association is not consistent. There are only a few examples of CYP2D6 involvement in toxicant mechanism of action, but this has not been extensively studied. Gene probe studies documented a number of genetic polymorphisms that underlie CYP2D6 metabolizer phenotypes. The EM group carries the wild-type (*1) or active (*2) variant alleles, while the PM group carries the *3, *4, *5, or *6 alleles, all of which code for a protein that has lower or null CYP2D6 activity. The current analysis characterizes (a) influence of genotype on phenotype based upon in vivo metabolism studies of probe drugs and (b) frequency of the major genotypes in different population groups is also characterized. These data were then incorporated into Monte Carlo modeling to simulate population distributions of CYP2D6 activity. This analysis reproduced the bimodal distributions commonly seen in phenotyping studies of Caucasians and found extensive population variability in enzyme activity, as indicated by the 9- to 56-fold difference between the PM modal median and the total population median CYP2D6 activity. This substantial degree of interindividual variability in CYP function indicates that assessments involving CYP2D6 substrates need to consider the full distribution of enzyme activity in refining estimates of internal dose in health assessments of xenobiotics.

Genetic polymorphism in paraoxonase 1 (PON1): Population distribution of PON1 activity.

Paraoxonase-1 (PON1) is a serum esterase that hydrolyzes the activated oxon form of several organophosphates. The central role of PON1 in detoxification of organophosphate (OP) pesticides was demonstrated in knockout mouse studies, suggesting that human variability in PON1 needs to be considered in health risk assessments involving exposure to these pesticides. The current analysis focused on two genetic loci in which polymorphisms demonstrated to affect PON1 activity. Detailed kinetic studies and population studies found that the *192Q (wild type) allele is more active toward some substrates (such as sarin, soman, and diazoxon) and less active toward others (such as paraoxon or chlorpyrifos) relative to the variant *192R allele. Another allele that affects activity is *55M; PON1 enzyme quantity, rather than specific activity or substrate preference, is altered. The *192R variant occurs commonly with a frequency of 25-64% across the populations analyzed. The *55M allele is less common, occurring in 5-40% of individuals depending upon the ethnic group studied. These activity and allele frequency data were incorporated into Monte Carlo simulations in which the frequency of both variant alleles was simultaneously modeled in Caucasian, African American, and Japanese populations. The resulting Monte Carlo activity distributions were bimodal for the substrate paraoxon with approximately fourfold differences between low- and high-activity modal medians. Differences in activity between total population median and 1st percentile were five- to sixfold. When sarin metabolic variability was simulated, the population distributions were unimodal. However, there was an even greater degree of interindividual variability (median to 1st percentile difference >20-fold). These results show that the combined effects of two PON1 allelic variants yielded a population distribution that is associated with a considerable degree of interindividual variability in enzyme activity. This indicates that assessments involving PON1 substrates need to evaluate polymorphism-related variability in enzyme activity to display the distribution of internal doses and adverse responses. This may best be achieved via physiologically based pharmacokinetic (PBPK) models that input PON1 activity distributions, such as those generated in this analysis, to simulate the range of oxon internal doses possible across the population.

Beta testing of a network-based health literacy program tailored for older adults with hypertension.

A touch screen-enabled "Personal Education Program" was modified to the "next generation" to capture self-medication behaviors of older adults with hypertension and assess related knowledge and self-efficacy. The program analyzes patient-entered information and delivers interactive educational content tailored to the reported behaviors. Summaries of self-reported symptoms, medication use (including frequency/time), drug interactions, and corrective strategies with an illustration of the drug interaction are printed to inform the provider before the primary care visit and for the patient to take home for self-study. After formative research during development and formal diagnostic and verification usability studies with advanced practice nurses and older adults, a beta test was conducted with older adults with hypertension over a 3-month period. Findings from the beta test suggest that older adult user satisfaction was high. Blood pressure declined over the four visits for 82% of the participants. The next generation of the Personal Education Program had a large effect size in increasing knowledge and self-efficacy for avoiding adverse self-medication behaviors. Behavior risk score did not change significantly but was significantly correlated with systolic blood pressure on the fourth visit. The positive results found in this small sample suggest that the next generation of the Personal Education Program could play a central role in facilitating patient-provider communication and medication adherence.