Associations of characteristics of renal transplant recipients with clinicians' perceptions of adherence to immunosuppressant therapy.

BACKGROUND: The objective of the study was to determine surveillance criteria for renal transplant recipients (RTRs) at highest risk for immunosuppressant therapy nonadherence. METHODS: Retrospective analyses were performed on follow-up data in the United States Renal Data System. Those who received transplants between January 1, 1995 and December 31, 2002, had at least 36 months of follow-up data, and did not receive a second renal transplant were included in the analyses. The risk of nonadherence was estimated by random effects logistic regression while controlling for age, gender, race, education, donor type, primary insurance, time since transplant, and immunosuppressant medications using the STATA software (College Station, TX). Association between nonadherence and graft failure was also examined. RESULTS: A total of 53,997 individuals met the inclusion criteria. About 6% of RTRs were reported nonadherent. Nonadherence risk increased with time posttransplant and decreased with age (P<0.001). RTRs who were male, nonwhite, or used mycophenolate mofetil or tacrolimus were more likely to be nonadherent with odds ratios (OR) of 1.36, 1.99, 1.13, and 1.31, respectively (P<0.05) than RTRs who used cyclosporine, steroids, azathioprine, or had Medicare (P<0.05). Nonadherent RTRs were more likely to experienced graft failure (P<0.001). CONCLUSIONS: Interventions to improve adherence should target younger RTRs, male RTRs, nonwhite RTRs, and those not on Medicare to reduce risk of graft failure.

Effects of a medication assistance program with medication therapy management on the health of renal transplant recipients.

PURPOSE: The effects of a medication assistance program with medication therapy management (MTM) on the clinical outcomes and health-related quality of life (HQOL) of renal transplant recipients were studied. METHODS: All renal transplant recipients who were enrolled in the Medication Access Program at the Medical College of Georgia for at least one year were included in the study. Patients' demographics, number of graft rejections (for one year pre-enrollment and one year post-enrollment), and diagnoses of hypertension, diabetes, and dyslipidemia were recorded and confirmed by medical and pharmacy records. The use of antihypertensive, antidiabetic, antilipemic, and immunosuppressant agents and laboratory values for fasting blood glucose, glycosylated hemoglobin (HbA(1c)), blood pressure, low-density-lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and serum immunosuppressant concentrations were identified for one year pre-enrollment and one year post-enrollment. HQOL was measured at the time of enrollment and one year post-enrollment. RESULTS: Thirty-six adult renal transplant recipients were included in the study. All patients had hypertension, 72% had dyslipidemia, and 42% had diabetes. Patients received significantly more antihypertensive agents post-enrollment versus pre-enrollment (p < 0.001) and significantly more antidiabetic agents (p = 0.004) and antilipemics (p = 0.001). Measures of fasting blood glucose, glycosylated hemoglobin, LDL cholesterol, total cholesterol, triglycerides, blood pressure, and number of graft rejections decreased from pre-enrollment levels (p < 0.01). A significantly greater number of patients reached target serum cyclosporine levels post-enrollment versus pre-enrollment (p = 0.008). HQOL was significantly increased one year post-enrollment (p < 0.01). CONCLUSION: A medication assistance program that included MTM services improved medication access, clinical outcomes, and HQOL in renal transplant recipients.

Predicting adherence to immunosuppressant therapy: a prospective analysis of the theory of planned behaviour.

BACKGROUND: The objective of this study was to increase the ability to predict renal transplant patients (RTPs) who are most likely to be non-adherent to their immunosuppressant therapy (IST). METHODS: One hundred and fifty-eight RTPs completed questionnaires assessing Theory of Planned Behaviour (TPB) variables (attitudes, subjective norms and perceived behavioural control) relevant to intentions to adhere to their IST, with the addition of a general measure of past adherence to medical advice. In the full sample, intentions to adhere to IST was the outcome variable. In a subsample of 70 RTPs, the primary outcome was IST adherence. RESULTS: TPB variables (attitudes, beta = 0.32, P < 0.01; perceived behavioural control, beta = 0.37, P < 0.01; but not subjective norms, beta = -0.001, ns) explained 41% of the variance in intentions to adhere to IST (P < 0.001). Past behaviour predicted perceived behavioural control (beta = 0.67, P < 0.001). Subsample analyses explained 33% (P < 0.001) of the variance in adherence, with intentions and past behaviour being the primary factors (P < 0.05). CONCLUSIONS: RTPs particularly at risk may be those who have a history of non-adherence to medical advice, especially when they have negative attitudes about IST adherence and feel they have little control over their medication-taking behaviour. Interventions to improve attitudes about IST adherence and control of adherence behaviour are needed.

Influence of economic and demographic factors on quality of life in renal transplant recipients.

BACKGROUND: The purpose of this study was to determine the influence of annual income, Medicare status, and demographic variables on the health-related quality of life (HQoL) of renal transplant recipients. METHODS: A cross-sectional survey was mailed to 146 Georgia renal transplant recipients who had functional grafts. Data were collected using the SF-12 Health Survey (version 2), a demographics survey, and 2003 tax documents. One-way ANOVAs and Pearson's R correlations were used to examine relationships between annual income, Medicare status, demographic variables and SF-12 scores. Significant variables were included in stepwise multiple regression analyses. RESULTS: Data from 130 participants (89% response rate) were collected. Recipients with no Medicare coverage had significantly higher scores on the Physical Functioning and Role Physical SF-12 scales (p = 0.005) compared to recipients with Medicare. Annual income was positively correlated with General Health (p < 0.05). Age and race were significant predictors of Vitality (p = 0.004) and Physical Component Summary (p < 0.001) scores. Age, race, and Medicare status were significant predictors of Physical Functioning and Role Physical scores (p < 0.001). Age, annual income, race, and years post-transplant were significant predictors of General Health score (p < 0.001). Age was the sole predictor of Bodily Pain score (p = 0.002), and marital status was the sole predictor of Social Functioning score (p = 0.005). CONCLUSIONS: Interventions designed to offset financial barriers may be needed to bolster renal transplant recipients' HQoL.

Is age associated with the number or types of medications prescribed to renal transplant recipients?

OBJECTIVES: To determine whether age influences the number or types of medications prescribed to younger (aged 18-64) and elderly (aged > or =65) renal transplant recipients 3 years posttransplant. DESIGN: A cross-sectional study involving renal transplant recipients. SETTING: Medical College of Georgia. PARTICIPANTS: A random sample of 100 elderly and 100 younger renal transplant recipients who received posttransplant care at the Medical College of Georgia, were on stable immunosuppressant therapy regimens, and were at least 3 years posttransplant. MEASUREMENTS: Medical and pharmacy data of recipients were evaluated for demographics; presence of a lipid-lowering agent; number of antihypertensives, immunosuppressants, antidiabetic agents, and total medications; number of rejections; dose per kilogram of immunosuppressant(s); infection-related hospitalizations; and measures of blood pressure, blood glucose, serum creatinine, serum tacrolimus/cyclosporine concentrations, total cholesterol, and triglycerides. RESULTS: Elderly recipients were more likely to have diabetes mellitus before the transplant and to develop diabetes mellitus afterwards (P=.04) and were prescribed more total medications (12.40+/-3.72 vs 10.25+/-4.07, P<.001) and antidiabetic agents (0.89+/-0.93 vs 0.42+/-0.77, P<.001) 3 years posttransplant than younger recipients. Elderly recipients also had fewer chronic rejections, more infection-related hospitalizations, lower diastolic blood pressure, and greater fasting blood glucose levels 3 years posttransplant (P<.05) than younger recipients. CONCLUSION: Future investigation should focus on deciphering the implications of the greater numbers of medications prescribed to elderly renal transplant recipients in terms of maximizing desired health outcomes (e.g., graft survival) and minimizing adverse drug-related experiences (e.g., infection).

A renal transplantation advanced pharmacy practice experience.

OBJECTIVES: To establish and evaluate an ambulatory care renal transplantation clinic advanced pharmacy practice experience (APPE). DESIGN: Students spend 5 weeks performing pharmaceutical care activities for renal transplant patients, presenting health-related topics, and conducting research. A paired t test was used to determine differences between students' pre- and post-APPE test scores. Standardized evaluations completed by the preceptor and the students were used to evaluate learning and the APPE. ASSESSMENT: Posttest scores were significantly higher than pretest scores (n = 17; 88.2 +/- 7.3 vs 55.9 +/- 22.4; p < 0.001). Overall, students found this APPE enjoyable and believed that it increased their knowledge concerning transplant medicine and patient care. CONCLUSION: With the recommendation that all transplant programs have clinical pharmacy services, it is imperative to train students to care for transplant patients. Information in this manuscript can be used as a guide for utilizing the combined resources from schools of pharmacy and transplantation centers to implement a renal transplant ambulatory care APPE.

Development of an instrument to measure professionalism.

OBJECTIVES: To develop and validate an instrument that measures professionalism among pharmacy students and recent graduates. METHODS: A pharmacy professionalism survey instrument developed by a focus group was pretested and then administered to all first-year pharmacy students enrolled in the University of Georgia College of Pharmacy and to recent pharmacy graduates who were taking the preparation course for the Georgia Pharmacy Law Examination and North American Pharmacist Licensure Examination. Participants were asked to indicate the extent to which they agreed or disagreed with each of 32 items using a 5-point Likert scale. RESULTS: One hundred thirty first-year pharmacy students and 101 pharmacy graduates participated in the survey. Statistical analysis identified 6 factors (subscales), which were later named excellence, respect for others, altruism, duty, accountability, and honor/integrity, the 6 tenets of professionalism. Item to total correlations ranged from 0.25 to 0.57 on the 6 factors (subscales), and reliability estimates ranged from 0.72 to 0.85 for the 6 factors and total scale. CONCLUSIONS: The Pharmacy Professionalism Instrument measures the 6 tenets of professionalism and exhibits satisfactory reliability measures. Future studies using this scale in other pharmacy populations are needed.

Modified-release tacrolimus.

OBJECTIVE: To review the pharmacokinetics, efficacy, adverse effects, and clinical trials of modified-release tacrolimus (MR-4) concerning its equivalence to non-modified-release tacrolimus. DATA SOURCES: A PubMed/MEDLINE search was conducted (1966-July 2005) using the following terms: MR-4, tacrolimus, FK506, Prograf, transplantation, calcineurin inhibitors, and immunosuppression. Additional data sources included meeting abstracts, bibliographies from identified publications, and information from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All English-language, published, randomized clinical trials evaluating MR-4 were included in this review. Clinical trials that used tacrolimus for the prevention of solid-organ graft rejection were also selected from the data sources. DATA SYNTHESIS: Studies demonstrated that MR-4 has pharmacokinetic profiles similar to those of tacrolimus in healthy volunteers, renal transplant recipients, and liver transplant recipients. Similar efficacy and safety profiles have also been demonstrated. Data also suggest that the target whole blood trough concentration range of MR-4 is similar to that of tacrolimus and that it is safe to convert from tacrolimus twice daily to MR-4 once daily using a 1:1 conversion. CONCLUSIONS: Short-term clinical trials indicated that MR-4 has efficacy and safety profiles similar to those of tacrolimus. MR-4's once-daily dosing offers an advantage over the currently available calcineurin inhibitors in preventing graft rejection. However, adherence studies with MR-4 that measure clinical and economic outcomes are needed.

Development and validation of the immunosuppressant therapy adherence instrument (ITAS).

A five-item scale was developed that asked respondents to indicate how often they were non-adherent to immunosuppressant therapy (IST) given a particular circumstance. Two hundred and twenty-two recipients completed the instrument. Validity of the scale was assessed by correlating composite item scores with refill record adherence rates (RRARs), serum immunosuppressant (IS) concentrations, graft rejection, and increased serum creatinine (SCr) levels. One scale item was deleted due to lack of response variability. Cronbach's alpha coefficient for the four-item scale was 0.81, demonstrating that the scale has acceptable reliability. All items loaded on a single principal component, suggesting that the scale measures a single adherence construct, which accounted for 64% of the scale items' variance. The four-item scale, adherence measured by IS RRARs, and "target" IS serum concentrations had positive correlations (p < 0.01). Item scores were shown to be negatively related to rejection occurrence and increased SCr (p < 0.05). The immunosuppressant therapy adherence scale is the first published, valid and reliable instrument that measures recipients IST adherence.

Patient factors associated with adherence to immunosuppressant therapy in renal transplant recipients.

PURPOSE: Factors associated with adherence to immunosuppressant therapy (IST) in renal transplant recipients were studied. METHODS: The Immunosuppressant Therapy Adherence Scale (ITAS) was completed by adult renal transplant recipients in Georgia. Those completing the ITAS were classified as adherent to IST if their ITAS score were 12 and nonadherent if their score was less than 12. The relationship between the dichotomized ITAS scores and patient variables that are readily available to clinicians, such as sex, age, kidney donor type, income, marital status, race or ethnicity, and time since transplantation, was assessed. The relationship of ITAS scores to patients' clinical and pharmacy data (e.g., graft rejection, serum IST concentrations, serum creatinine [SCr] concentrations, and pharmacy refill-based adherence rates) was also assessed. RESULTS: One hundred thirty-seven patients completed the ITAS. Eighty-nine patients (65%) were adherent to IST, and the remaining 48 (35%) were nonadherent. Patient sex was unrelated to adherence. Compared with nonadherent patients, adherent patients tended to be younger, to take cyclosporine, to have lower incomes, to have received their transplant more recently, to have targeted immunosuppressant concentrations, to have greater refill-based adherence rates, and to be less likely to exhibit an increase in SCr concentration (p < 0.05). There was no significant difference in the number of rejections between adherent and nonadherent patients. CONCLUSION: Patient age, income, time since transplantation, and the immunosuppressant agent prescribed were associated with IST adherence.

Medicare-approved drug discount cards and prescription drug prices.

PURPOSE: Prescription drug prices with and without the use of Medicare-approved drug discount card programs (MADDCs) to purchase medications were studied. METHODS: The Medicare.gov Web site was used to determine if the 200 most frequently prescribed drugs in the United States in 2003 were covered by a MADDC. The lowest and highest MADDC prices at local and mail-order pharmacies and the corresponding non-MADDC prices at the same community pharmacies or an Internet pharmacy, respectively, were determined. Wilcoxon signed rank tests were used to determine if there was a difference between non-MADDC medication prices and MADDC prices. RESULTS: Of the top 200 medications prescribed in 2003, 192 (96%) and 189 (94.5%) were covered by at least one MADDC in a local pharmacy or mail-order pharmacy, respectively. Overall, MADDCs saved money compared with purchasing medications without a MADDC (p < 0.001). However, a MADDC resulted in a higher price than the retail non-MADDC price for 61 (31.8%) of the prescription medications at local pharmacies, and using a MADDC at a mail-order pharmacy resulted in a higher price than the Internet pharmacy non-MADDC price for 143 (75.7%) of the drugs. CONCLUSION: MADDC prices for common prescription medications were generally lower than prices when MADDCs were not used. The highest mail-order MADDC prices were often higher than Internet non-MADDC prices.

Medicare-approved drug discount cards and renal transplant patients: how much can these cards reduce prescription costs?

BACKGROUND: Post-transplant prescription medications are expensive, often costing over 12,000 dollars annually. Many solid-organ transplant patients have Medicare coverage and patients enrolled in Medicare-approved drug discount card (MADDC) programs may be able to receive prescription medications at a reduced price. However, many transplant healthcare practitioners are unaware of the utility of MADDCs. The purpose of this study was to determine whether enrolling renal transplant patients (RTPs) into a MADDC produces significant savings in prescription costs. METHODS: Two Medicare RTPs, with prescription medication profiles representative of an RTP within 3 months post-transplant and an RTP greater than 5 yr post-transplant, were randomly selected from the Medication Access Program's database. Cost benefit analyses were from the patients' perspective and were performed using the: (i) prescription cost from the Medicare website of MADDCs that listed the greatest and least prescription costs compared with the retail cash price of the same prescription without using the MADDCs; and (ii) MADDCs' annual enrollment fee. The potential cost difference of using MADDCs and not using MADDCs to purchase the prescription medications were calculated. RESULTS: RTPs' monthly out-of-pocket cost for prescription medications ranged from 162 dollars to 340 dollars, and MADDCs offered discounts of 20-37% from retail prices; thus outweighing the MADDC enrollment cost. CONCLUSION: MADDCs, when selected and used appropriately, can reduce prescription medication cost for RTPs. Card selection is of great importance as discount rates vary greatly among cards, and only under restricted circumstances is a patient allowed to switch to another card. It is imperative that practitioners are aware of these programs and utilize cost-effective prescribing practices.

Comparing renal transplant patients' adherence to free cyclosporine and free tacrolimus immunosuppressant therapy.

BACKGROUND: The purpose of this study is to determine if there is a difference in renal transplant patients' (RTPs) adherence to cyclosporine compared to tacrolimus when medications are supplied free to the RTPs. METHODS: Adult primary RTPs were included in the study if they received a renal transplant at the Medical College of Georgia (MCG) from June 1998 through August 2001 and received their first post-transplant year of follow-up care at MCG and free cyclosporine or free tacrolimus from the MCG outpatient pharmacy. Adherence was estimated by comparing each RTPs' tacrolimus or cyclosporine pharmacy refill records to the prescribed regimen for 12 months after transplant. Patients' cyclosporine and tacrolimus serum concentrations were used to validate adherence. Kaplan-Meier analysis was used to estimate the fraction of RTPs remaining adherent and to compare the mean time RTPs were adherent in each group (cyclosporine vs. tacrolimus). RESULTS: Thirty-three RTPs were included in the study, 25 (76%) received cyclosporine and eight received tacrolimus. The mean time to the first non-adherent month was 8 months post-transplant. At 12-months post-transplant, approximately 42% of the patients remained adherent. A greater percentage of the patients who received tacrolimus remained adherent compared with those who were taking cyclosporine (63% vs. 33%, p < 0.05). Approximately 75% of non-adherent patients were found to have subtarget drug concentrations, and only 24% of adherent patients had subtarget levels (p < 0.01). CONCLUSIONS: When provided free, patients are more adherent to tacrolimus than cyclosporine. Regardless of treatment, intensive efforts to increase adherence should be implemented.

Development and validation of an immunosuppressant therapy adherence barrier instrument.

BACKGROUND: To decrease allograft rejection as a result of non-adherence to immunosuppressant therapy (IST), a valid and reliable instrument that measures solid organ transplant patients' adherence barriers is needed. METHODS: An immunosuppressant therapy barrier scale (ITBS) was developed to assess transplant patients' perceived barriers to IST adherence and was completed by 222 transplant patients who lived in Georgia, USA. A renal transplant population subset was used to test the ITBS reliability and validity. Scale reliability was estimated using Cronbach's alpha coefficient of internal consistency; scale dimensionality was assessed using principal components analysis. The criterion-related validity of the scale was assessed by relating subscale scores to adherence measures and graft rejection. Nomological validity was assessed by relating barrier subscales to specific patient factors. RESULTS: Two subscales that represented 'controllable' and 'uncontrollable' barriers were found. Cronbach's alpha coefficients demonstrated acceptable reliabilities of 0.93, 0.86 and 0.91 for the 'uncontrollable' and 'controllable' subscales, and for the entire ITBS, respectively. The ITBS subscales correlated negatively with a self-reported measure of IST adherence, IST serum concentrations and IST pharmacy refill adherence rate (P<0.01). The 'uncontrollable barrier' subscale was positively correlated to kidney graft rejection (P<0.01), thus demonstrating the ITBS's validity. Males and older patients reported more adherence barriers (P<0.05). CONCLUSIONS: The ITBS is a reliable and valid instrument that can be used to measure patients' perceived barriers to IST adherence.

Identification of medication-adherence barriers and strategies to increase adherence in recipients of renal transplants.

One hundred randomly selected renal transplant centers (RTCs) were surveyed concerning barriers to medication adherence by recipents of renal transplants (RTRs). Responders were asked to list factors that they believe decrease RTRs' medication adherence. Survey responses were used to develop another survey, which was mailed to a different set of 100 RTCs. Barriers identified included issues concerning the particular medication prescribed, patient knowledge and comprehension concerning how to take the medication, patients' desire or motivation to take the medication, patient-health care professional relationship, and the ability of the caregiver to deliver optimum care. Barriers that received at least a 75% agreement were given to a multidisciplinary focus group, who developed strategies to circumvent the barriers. Strategies addressing barriers are discussed.

Effect of clinical pharmacy services on the blood pressure of African-American renal transplant patients.

OBJECTIVE: The objective of this study was to determine if African-American renal transplant patients who received direct patient care from a clinical pharmacist had better blood pressure control compared to African-American renal transplant patients who did not have clinical pharmacy services. METHODS: Renal transplant patients were prospectively randomized into an intervention group or a control group. Patients in the intervention group received clinical pharmacy services that included a clinical pharmacist performing patient medication reviews, with emphasis on preventing or resolving medication-related problems and providing medication recommendations. Patients in the control group received routine clinic services, but had no clinical pharmacist interaction. Analysis was performed to detect differences between the intervention and control groups in baseline and quarterly systolic blood pressure (SBP) and diastolic blood pressure (DBP) for one year post-study enrollment. RESULTS: There were no differences between the intervention (N = 13) and control (N = 10) groups in baseline blood pressures or in the percentage of hypertensive patients. Significant differences in the change in SBP and DBP from baseline between the intervention and control groups were observed at the second, third, and fourth quarters of the study, favoring the intervention group (P < .01). Mean SBP was significantly lower in the intervention group at the second (137.8 +/- 15.0 vs 168.9 +/- 15.3), third (135.9 +/- 11.7 vs 164.6 +/- 20.1), and fourth (145.3 +/- 16.8 vs 175.8 +/- 33.9) quarters of the study (P < .05). Mean DBP was significantly lower in the intervention group at the second (76.0 +/- 11.8 vs 84.9 +/- 6.1) and fourth (77.0 +/- 10.2 vs 91.8 +/- 12.0) quarters (P < .05). CONCLUSION: Direct patient care services provided by a clinical pharmacist, in addition to routine clinical services, have a positive effect on the blood pressure of African-American renal transplant patients. A multidisciplinary team that includes a clinical pharmacist is beneficial to patient care.

Enhancing transplant patients' adherence to medication therapy.

Despite the importance of proper medication use, many transplant patients do not take their medications correctly. Non-adherence to medication therapy leads to adverse consequences, and practitioners should encourage adherence by transplant patients. This manuscript discusses several aspects of medication taking behavior including: (1) methods of identifying medication non-adherence; (2) models used to identify possible determinants of medication taking behavior; (3) strategies to educate patients concerning their therapy; (4) factors promoting adherence and non-adherence; and (5) practical interventions that we, as practitioners, can employ to enhance adult and pediatric transplant patients' adherence to therapy. By using the strategies suggested, transplant patients' adherence to medication therapy may be enhanced and patients' quality of life improved.