Chronic Oral Medication Research Articles

The appointment-based model in community pharmacies: Patient demographics and reimbursable clinical services uptake in Ontario.

Community pharmacies typically require patients to request medication refills. The appointment-based model (ABM) is a proactive approach that synchronizes refills and schedules patient-pharmacist appointments. These appointments provide opportunities for medication reviews, medication optimization and health promotion services. The primary aim of this study was to describe the types of patients who received an ABM service in a community pharmacy in Ontario in 2017. The secondary aim was to describe reimbursable clinical service uptake. In September 2017, the ABM was implemented across 3 Ontario community pharmacies within a Canadian pharmacy banner. Patients who filled at least 1 chronic oral medication and consented to enrolment were eligible. In December 2018, data were extracted from pharmacies using pharmacy management software. Descriptive statistics and frequencies were generated. Analysis of 131 patients (51.1% female; mean ± SD age 70.8 ± 10.5 years) revealed patients were dispensed a mean ± SD of 5.1 ± 2.7 medications, and 73 (55.7%) experienced polypharmacy. Hypertension (87.8%) and dyslipidemia (68.7%) were the most common medical conditions. There were 74 (56.5%) patients who received ≥1 medication review service (MedsCheck). Of 79 unique drug therapy problems (DTPs) identified, the most common categories related to patients needing additional drug therapy and adverse drug reactions. Patients enrolled in the ABM were generally older adults experiencing polypharmacy. The ABM presented opportunities for DTP identification and delivery of reimbursed services. Findings support continued exploration of the ABM to support integration of clinical services within community practice.

Study Protocol for the Evaluation of Multidisciplinary Medication Reconciliation Service in Adult Patients Undergoing Thoracic and Cardiovascular Surgery (The MERITS Study): A Single-Center Controlled before-and-after Study.

Medication reconciliation (MR), which is widely implemented worldwide, aims to improve patient safety to reduce the medication errors during care transition. Despite its widespread use, MR has not yet been implemented in the Republic of Korea, and its effectiveness has not been studied. We aimed to evaluate the impact of a multidisciplinary MR service in older patients undergoing thoracic and cardiovascular surgery. This is a single-center, prospective, controlled, before-and-after study of adult patients taking at least one chronic oral medication. Depending on the period of each patient's participation, they will be allocated to an intervention group or control group. Patients in the intervention group will receive multidisciplinary MR, and those in the control group will receive usual care. The primary outcome is to assess the impact of the MR service on medication discrepancies between the best possible medication history and medication orders at care transition. Secondary outcomes include the incidence rate of medication discrepancies at each transition, the discrepancy rate between the sources of information, the impact of MR on medication appropriateness index score, drug-related problems, 30-day mortality, the emergency department visit rate, readmission rate after discharge, the rate and acceptability of pharmacists' intervention during hospitalization, and patients' satisfaction.

Low Medication Knowledge and Adherence to Oral Chronic Medications among Patients Attending Community Pharmacies: A Cross-Sectional Study in a Low-Income Country.

Objective To investigate the level of knowledge, medication adherence, and the relationship among patients taking chronic oral medication and attending community pharmacies in Gondar, Northwest Ethiopia. Methods A cross-sectional study was conducted among adult chronic disease patients who were taking oral medications and getting service in 19 community pharmacies in Gondar City, Northwest Ethiopia. Patients' medication knowledge and adherence were assessed using interviewer-administered validated questionnaires. Results Of the 402 study participants (mean ± SD age = 44.7 ± 16.9 years, range = 18–86 years), 53.2% were males, 84.8% were aged <65 years, and 60.7% had high school education and above. About 348 (88.6%) respondents have used oral medications for more than one year. Less than half of respondents have good medication knowledge (n = 54, 38.3%) and were adherent to their medication (n = 158, 39.3%). Chronic disease patients with high school and above education are 5.35 times (95% CI: 3.231–8.857, p < 0.001) more likely to have good knowledge of their medication and having good medication knowledge was linked to higher medication adherence (AOR, 95% CI = 10.300 [6.16517.209]; p < 0.001). A statistically significant correlation was observed between the scores of medication knowledge and adherence (r = −0.471, p < 0.001). Conclusion The majority of patients on oral chronic medications and attending community pharmacies in Gondar town do not have good medication knowledge and were nonadherent. Community pharmacists need to engage in medication counseling to improve medication knowledge and adherence of chronic disease patients.

The pharmacokinetics of oral carbamazepine in rats dosed using an automated drug delivery system.

Pharmacokinetics (PK) of antiseizure drugs differ considerably between rats and humans. Rodents require larger and more frequent doses to maintain therapeutic drug levels. This study uses the antiseizure drug (ASD) carbamazepine (CBZ) to validate the application of a previously described automated drug delivery system for delivering chronic oral medication to rats. Treatment-naive, male Sprague-Dawley rats were treated with oral CBZ, 75mg/kg every 6hours for 10days, via the automated feeder. Blood samples were collected on day 0 (acute), day 2 (steady-state), and day 9 (chronic) and used to measure plasma CBZ and carbamazepine-10,11-epoxide (CBZ-E) concentrations via high-performance liquid chromatography. The PK of CBZ and CBZ-E were modeled using Monolix v2018R1. The acute and chronic tolerability of CBZ was evaluated using the open field test. CBZ and CBZ-E concentrations were best described by a one-compartment parent-metabolite model with first-order absorption and elimination kinetics. Observed and predicted CBZ concentrations were maintained within the therapeutic window (4-12μg/mL) for the duration of the study. There was no change in open-field test activity following acute or chronic oral dosing of 75mg/kg CBZ compared to a pretreatment baseline (P>0.4). Oral administration of CBZ dosed q.i.d. in rats using an automated drug delivery system results in therapeutic concentrations of CBZ and its active metabolite. This study represents the first PK validation for this previously described preclinical drug delivery system.

Commentary on "The impact of nonadherence to antiseizure drugs on seizure outcomes in an animal model of epilepsy".

The aim of this study was to understand the impact of human patterns of antiseizure drug (ASD) nonadherence on seizure control using a novel oral drug-delivery system in the kainate rat model of epilepsy. The main finding is that nonadherence to the ASD carbamazepine is associated with significant but reversible effects on seizure control, which shows that the model replicates clinical findings. As such, the study uses a reverse translational approach to validate the experimental paradigm chosen for these interesting series of experiments. As suggested by the authors, the experimental results demonstrate that animal studies of nonadherence can yield potentially important and translatable insights into the consequences of nonadherence on seizure control. An unexpected finding of the study was the lack of complete seizure control in most animals in the 100% perfect adherence group, indicating that the chronic epilepsy model used closely replicates mesial temporal lobe epilepsy with a high level of drug resistance. In addition to the experimental design of this first-of-a-kind pilot study, I was particularly impressed by the computer-controlled automated delivery system that provides tight control over chronic oral medication dosing in rats. In this respect, it is highly advantageous compared to conventional drug administration via the food or drinking water in rodents, which is associated with large circadian variation in drug intake.1 The innovative open-source drug-delivery system has been previously described in detail by Kyle Thomson and Steve White2 to allow its use by other investigators, which is to be saluted. I have no conflicts of interest to disclose. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Medication burden attributable to chronic co-morbid conditions in the very old and vulnerable.

ObjectivePolypharmacy is common in older patients but relationships between polypharmacy and common co-morbid conditions have not been elucidated. Our goal was to determine relationships between daily oral medication use and common co-morbid disease dyads and triads using comprehensive medication and diagnostic data from a national sample of nursing homes (NH).DesignRetrospective, cross-sectional study.SettingNationally representative sample of U.S. Nursing Homes.ParticipantsNationally representative sample of long-term stay residents (n = 11734, 75% women) aged 65 years or older.MeasurementsDiagnosis and medication data were analyzed. Proportion of daily oral medication intake attributed to treatment of common two-(dyads) and three-disease (triad) combinations and “health maintenance” agents (vitamins, dietary supplements, stool softeners without related diagnoses) was determined.ResultsOlder NH residents received slightly >8 oral medications/day with the number related to number of medical diagnoses (p < .0001). One third of chronic oral medication intake/day (excluding health maintenance agents) could be attributed to dyad combinations and about half to triad combinations despite an average of 5 other diagnoses. Triads were comprised of hypertension +/- arthritis +/- vascular disease, +/-depression, +/- osteoporosis +/- gastroesophageal reflux disease and +/- diabetes. Health maintenance agents accounted for 15–17% of daily oral medication intake (1.4 medications) such that almost two-thirds of daily oral medications were attributable to disease triads plus health maintenance. Fewer medications were prescribed for NH residents over age 85 (decreased ACE inhibitor and HMG CoA reductase inhibitor USE (p < .001)) while use of Alzheimer medications was higher (p < .01).ConclusionsA large fraction of daily oral medications were attributed to management of common co-morbid disease dyads and triads. Efforts to reduce polypharmacy and unwanted medication interactions could focus on regimens for common co-morbid dyads and triads in varying populations.

Influence of Titration of Neurohormonal Antagonists and Blood Pressure Reduction on Renal Function and Decongestion in Decompensated Heart Failure

Reduction in systolic blood pressure (SBP reduction) during the treatment of acute decompensated heart failure is strongly and independently associated with worsening renal function. Our objective was to determine whether SBP reduction or titration of oral neurohormonal antagonists during acute decompensated heart failure treatment negatively influences diuresis and decongestion. SBP reduction was evaluated from admission to discharge in consecutive acute decompensated heart failure admissions (n=656). Diuresis and decongestion were examined across a range of parameters, such as diuretic efficiency, fluid output, hemoconcentration, and diuretic dose. The average reduction in SBP was 14.4 ± 19.4 mm Hg, and 77.6% of the population had discharge SBP lower than admission. SBP reduction was strongly associated with worsening renal function (odds ratio, 1.9; 95% confidence interval, 1.2-2.9; P=0.004), a finding that persisted after adjusting for parameters of diuresis and decongestion (odds ratio, 2.0; 95% confidence interval, 1.3-3.2; P=0.002). However, SBP reduction did not negatively affect diuresis or decongestion (P ≥ 0.25 for all parameters). Uptitration of neurohormonal antagonists occurred in >50% of admissions and was associated with a modest additional reduction in blood pressure (≤ 5.6 mm Hg). Notably, worsening renal function was not increased, and diuretic efficiency was significantly improved with the uptitration of neurohormonal antagonists. Despite a higher rate of worsening renal function, blood pressure reduction was not associated with worsening of diuresis or decongestion. Furthermore, titration of oral neurohormonal antagonists was actually associated with improved diuresis in this cohort. These results provide reassurance that the guideline-recommended titration of chronic oral medication during acute decompensated heart failure hospitalization may not be antagonistic to the short-term goal of decongestion.

Standardizing Terminology and Definitions of Medication Adherence and Persistence in Research Employing Electronic Databases

To propose a unifying set of definitions for prescription adherence research utilizing electronic health record prescribing databases, prescription dispensing databases, and pharmacy claims databases and to provide a conceptual framework to operationalize these definitions consistently across studies. We reviewed recent literature to identify definitions in electronic database studies of prescription-filling patterns for chronic oral medications. We then develop a conceptual model and propose standardized terminology and definitions to describe prescription-filling behavior from electronic databases. The conceptual model we propose defines 2 separate constructs: medication adherence and persistence. We define primary and secondary adherence as distinct subtypes of adherence. Metrics for estimating secondary adherence are discussed and critiqued, including a newer metric (New Prescription Medication Gap measure) that enables estimation of both primary and secondary adherence. Terminology currently used in prescription adherence research employing electronic databases lacks consistency. We propose a clear, consistent, broadly applicable conceptual model and terminology for such studies. The model and definitions facilitate research utilizing electronic medication prescribing, dispensing, and/or claims databases and encompasses the entire continuum of prescription-filling behavior. Employing conceptually clear and consistent terminology to define medication adherence and persistence will facilitate future comparative effectiveness research and meta-analytic studies that utilize electronic prescription and dispensing records.

Impact of a Text Messaging Pilot Program on Patient Medication Adherence

BackgroundMedication nonadherence is a well-recognized challenge associated with poor health outcomes and increased utilization of health care resources. Although many different behavioral and educational strategies are available to improve patient medication adherence, technological advances, including cell phone text messaging, represent new and innovative modalities to improve adherence and overall health outcomes. ObjectiveTo evaluate medication adherence among patients opting to receive text message medication reminders and a well-matched control cohort. MethodsThis retrospective, observational cohort analysis compared medication adherence of members who opted-in to the text message medication reminder program and a matched control cohort using data from a member portal database and electronic pharmacy claims of a national pharmacy benefit manager with commercial and Medicare membership. Continuously enrolled members who opted to receive at least 1 medication-specific dosage reminder for a chronic oral medication of interest and had at least 1 pharmacy claim for the same chronic oral medication of interest were included. Matching was based on medication therapeutic class, then on propensity score (including variables of age, sex, health plan, Chronic Disease Score, distinct medication count, average baseline medication adherence, and duration of therapy). The primary outcome was chronic oral medication adherence, measured as the proportion of days covered (PDC), between January 1, 2011, and August 31, 2011. Analyses comparing cohorts were conducted using paired t tests and the McNemar test. ResultsAfter implementation of the text messaging program, the mean (SD) PDC was significantly higher for the text message cohort (n = 290) than for the control cohort (n = 290) (0.85 [0.20] vs 0.77 [0.28], respectively; P < 0.001). Of those members identified with a chronic oral antidiabetes medication, the mean PDC was significantly higher in the text message cohort than in the control cohort (0.91 [0.14] vs 0.82 [0.21]; P = 0.029). Significant differences in mean PDC were also seen in members who opted to receive text message reminders for β-blocker therapy over members in the control cohort (0.88 [0.18] vs 0.71 [0.29]; P = 0.006). ConclusionsFindings suggest that members opting into a text message reminder program have significantly higher chronic oral medication adherence compared with members not opting to receive medication-specific text message reminders, and that the use of a text message reminder program assists in preserving higher rates of adherence over time.

Simulation of the apparent effects of mebanazine on growth hormone by pair-feeding of control animals.

Abstract The degree and duration of insulin hypoglycaemia was potentiated by chronic oral medication with mebanazine in rats. Hypophysectomy alone increased sensitivity to insulin but did not abolish the potentiating effect of mebanazine. Chronic mebanazine treatment (15 mg/kg/day) for 6 weeks markedly reduced weight gain, food and water consumption and pituitary growth hormone content, but the results were not significantly different from those in unmedicated pair-fed controls. Similarly, immature rats treated with mebanazine had a significant reduction in the width of the tibial epiphysial cartilage but this was not different from that in pair-fed animals. After 18 h of fasting, acute administration of mebanazine had little effect on food consumption in the 2 h period following dosing but a significant effect over 24 h. In fed rats mebanazine in a single oral dose significantly reduced eating in the following 6 h. Treatment with mebanazine at 2·5 mg/kg for 15 days significantly reduced food intake but did not potentiate insulin hypoglycaemia. From the results it would appear that previous suggestions that mebanazine specifically interferes with growth hormone release are incorrect and the findings emphasize the importance of measuring food intake in experiments of long duration.

Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation

Some patients with Brugada syndrome experience an electrical storm of ventricular fibrillation (VF). The purpose of this study was to investigate the clinical, laboratory, electrocardiographic, and electrophysiologic characteristics, acute and subsequent chronic treatment, and follow-up data of patients with Brugada syndrome associated with electrical storm of VF. Sixty-seven patients with Brugada syndrome (65 men and 2 women, age 46 +/- 14 years) were divided into three groups: 7 patients with a history of electrical storm of VF (group I), 39 symptomatic patients with documented VF and/or syncope (group II), and 21 asymptomatic patients (group III). Electrical storm was defined as three or more episodes of VF per day recorded by the memory of an implantable cardioverter-defibrillator. No significant differences were observed among the three groups with regard to clinical (age at diagnosis, familial history of sudden cardiac death), laboratory (SCN5A mutation and serum potassium level), electrocardiographic and electrophysiologic characteristics, and follow-up duration after diagnosis. However, arrhythmic events during follow-up after diagnosis and number of arrhythmic events per patient were significantly higher in group I compared with groups II and III. Isoproterenol infusion (0.003 +/- 0.003 microg/kg/min for 24 +/- 13 days) completely suppressed electrical storm of VF in all five patients treated and was successfully replaced with oral medications, including denopamine, quinidine, isoproterenol, cilostazol, and bepridil alone or in combination. No specifically clinical, laboratory, electrocardiographic, and electrophysiologic characteristics were recognized in patients with Brugada syndrome associated with electrical storm of VF. Isoproterenol infusion was effective as an acute treatment in suppressing electrical storm of VF and was successfully replaced with chronic oral medications.

Gaps in cardiovascular medication taking

To search for major gaps in medication-taking behavior predisposing patients to cardiovascular morbidity and mortality. Convenience sample; cohort prospectively followed for < or = 5 months. General internal medicine and cardiology clinics in a university medical center. From among 893 patients, the authors identified 132 eligible individuals and entered 33 subjects (25%) with chronic cardiovascular conditions, 1-3 chronic oral medications for these conditions, overall regimen of < or = 6 drugs, regular visits at 1-3-month intervals, literacy in English, willingness to use electronic monitors, and physician permission to participate. Medication compliance rates and patterns by patient self-report, physician estimates, pill count, and electronic monitoring of pill vial opening. Despite moderately complex regimens (5.4 +/- 0.5 pills daily; range 1-11), most subjects took most medications according to the prescription: median intervals between pill vial openings were 1.00, 0.50, and 0.43 days for once, twice, and three times daily dosing, respectively. Medication-taking gaps of > or = 2 times the prescribed interdosing interval occurred for 48% of the patients. Patients' dosing patterns often produced "uncovered" intervals (mean duration 3.7 days, range 0-25) with doubtful pharmacologic effectiveness. These lapses were underestimated by patients and poorly perceived by their treating physicians, despite familiarity with their care. Baseline sociodemographic, psychosocial, medical system, or clinical characteristics did not predict the patterns or degrees of medication noncompliance. Major treatment gaps occur frequently, even in carefully selected ambulatory populations, and generally escape detection. The compliance patterns and gaps may contribute to reported excesses of cardiovascular morbidity and mortality.