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.     

肾移植受者应对方式对服药依从性及自我管理的影响

目的探讨肾移植受者疾病应对方式、服药依从性及其自我管理的特点,并分析应对方式对服药依从性和自我管理依从性的影响。 方法采用便利抽样选取2019年3月至5月广州医科大学附属第三医院器官移植随访门诊就诊的肾移植受者作为研究对象。采用一般情况调查表、医学应对问卷、免疫抑制剂依从性Basel评估量表(BAASIS)及肾移植受者自我管理调查量表作为调查工具。所有问卷调查均在肾移植受者门诊随访时进行。采用成组t检验比较肾移植组和慢病常模组面对、回避和屈服因子得分。应用分层回归方程分析肾移植受者应对方式对服药依从性和自我管理的影响。P<0.05为差异有统计学意义。 结果肾移植受者面对因子得分[(19.8±2.9)分]最高。肾移植组和慢病常模组回避因子得分分别为(15.1±2.7)和(14.4±3.0)分,差异有统计学意义(t＝-2.320,P<0.05)。肾移植受者BAASIS得分平均为(22.2±2.6)分,125例受者中53例(42.4%)受者服药依从性好。36例(28.8%)曾在过去1个月中至少漏服1次免疫抑制剂;19例(15.2%)在过去1个月中曾出现至少1次连续漏服状况;63例(50.4%)曾在过去1个月中提前或推迟2 h服药;9例(7.2%)曾不按医嘱剂量服药。肾移植受者自我管理总得分为(91±8)分,其中68例(54.4%)自我管理水平良好,57例(45.6%)自我管理处于中等水平。受者饮食、治疗、躯体活动和社会心理管理得分分别为(29.5±3.0)、(33.4±3.4)、(15.7±2.1)和(12.4±1.6)分。面对、回避和屈服3个变量分别解释服药依从性总变异的8.6%,治疗管理总变异的13.7%,躯体活动管理总变异的7.0%,社会心理管理总变异的25.0%,整体自我管理总变异的15.0%。服药依从性的预测因子为屈服(β＝-0.252,P<0.01),饮食管理的预测因子为面对(β＝0.212,P<0.05),治疗管理的预测因子为面对(β＝0.348,P<0.01),躯体活动管理的预测因子为面对(β＝0.255,P<0.01),社会心理管理的预测因子为面对和屈服(β＝0.394和-0.271,P均<0.01),整体自我管理的预测因子为面对(β＝0.365,P<0.01)。 结论肾移植受者应对方式是服药依从性和自我管理的重要影响因素,应重视其对待疾病的态度和方式,及时转换其消极的应对策略,以提高其服药依从性和自我管理水平。     

Factors related to immunosuppressant medication adherence in renal transplant recipients

Chisholm‐Burns M, Pinsky B, Parker G, Johnson P, Arcona S, Buzinec P, Chakravarti P, Good M, Cooper M. Factors related to immunosuppressant medication adherence in renal transplant recipients. Abstract: Non‐adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient‐reported data were collected through a cross‐sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs’ beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy‐seven RTRs were non‐adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18–29 yr were more likely to be non‐adherent than recipients 46–64 yr old (p ≤ 0.001). Non‐adherent RTRs had greater adherence barriers than adherent RTRs (p < 0.001). Adherent RTRs believed their ISMs were more necessary than non‐adherent RTRs (p < 0.001), while non‐adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p < 0.001). Non‐adherent RTRs had lower life satisfaction (p < 0.001). Non‐adherence is significantly associated with patients’ beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed.     

Medication understanding,non‐adherence,and clinical outcomes among adult kidney transplant recipients

We sought to evaluate the prevalence of medication understanding and non‐adherence of entire drug regimens among kidney transplantation (KT) recipients and to examine associations of these exposures with clinical outcomes. Structured, in‐person interviews were conducted with 99 adult KT recipients between 2011 and 2012 at two transplant centers in Chicago, IL; and Atlanta, GA. Nearly, one‐quarter (24%) of participants had limited literacy as measured by the Rapid Estimate of Adult Literacy in Medicine test; patients took a mean of 10 (SD=4) medications and 32% had a medication change within the last month. On average, patients knew what 91% of their medications were for (self‐report) and demonstrated proper dosing (via observed demonstration) for 83% of medications. Overall, 35% were non‐adherent based on either self‐report or tacrolimus level. In multivariable analyses, fewer months since transplant and limited literacy were associated with non‐adherence (all P<.05). Patients with minority race, a higher number of medications, and mild cognitive impairment had significantly lower treatment knowledge scores. Non‐white race and lower income were associated with higher rates of hospitalization within a year following the interview. The identification of factors that predispose KT recipients to medication misunderstanding, non‐adherence, and hospitalization could help target appropriate self‐care interventions.     

Medication adherence and rejection rates in older vs younger adult liver transplant recipients

A growing number of older adults are undergoing liver transplantation (LT) in the United States. In some settings, it is thought that adherence declines with age. This retrospective study examined adherence and clinical outcomes in older vs younger adult LT recipients. Medical records of adult LT recipients from 2009 to 2012 from a single urban center were reviewed. The medication level variability index (MLVI) was the predefined primary outcome, with nonadherence defined as MLVI >2.5. The secondary outcome was incidence of rejection. Outcomes were evaluated starting 1 year post‐LT until 2015. A total of 42 of 248 patients were ≥65 at transplant. Older adults had significantly better adherence than younger ones (65%≥65 were adherent vs 42% younger adults; chi‐square two‐tailed P=.02). Survival analyses of rejection between age groups censored by time since transplant showed no difference among the four age groups (χ²=0.84, P=.84). Older age was not found to be a risk factor for reduced adherence or graft rejection in patients surviving at least 1 year post‐LT.     

Determining the effect of immunosuppressant adherence on graft failure risk among renal transplant recipients

The objective was to use the United States Renal Data System (USRDS) to quantify the relationship between immunosuppressant therapy (IST) adherence and risk of graft failure among adult renal transplant recipients (RTRs). A secondary objective was to examine the relationship among select patient characteristics and IST adherence. The study sample included adult RTRs who: received primary transplant between January 1, 1999 and December 31, 2005; experienced graft survival for at least 12 months post‐transplant and had at least 12 months of data in the USRDS; utilized Medicare coverage for IST; and were prescribed cyclosporine or tacrolimus. IST adherence was measured by medication possession ratio (MPR). Pearson chi‐square tests were used to examine associations between patient characteristics and MPR quartiles. Cox proportional hazards regression was used to assess relationships among time to graft failure, MPR, and patient characteristics. Thirty‐one thousand nine hundred and thirteen RTRs met inclusion criteria. Older age, female gender, white race, deceased donors, and tacrolimus were associated with greater adherence (p < 0.001). Cox proportional hazard modeling indicated greater adherence, white race, and having a living donor were significantly associated with longer graft survival (p < 0.05). Future prospective studies should further examine the clinical significance of IST nonadherence as it relates to graft failure.     

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.     

Medication adherence in chronic disease: issues in posttransplant immunosuppression

Poor medication adherence is a widespread problem that undermines the potential benefits of medical treatment. Typical adherence rates among chronic disease patients are approximately 50%, and these low adherence rates have a substantial economic impact, estimated at $100 to $300 billion annually. Nonadherence to immunosuppressants among transplant recipients is surprisingly frequent, and the consequences are serious. Among adult renal transplant patients, the median rate of nonadherence is approximately 22% and is associated with acute rejection episodes and approximately 36% of all graft losses. In the United States, nonadherence results in an estimated 903 episodes of acute rejection and 1319 renal transplants failures annually, costing approximately $15 million and $100 million, respectively. Drug regimen complexity is known to impact adherence. Research demonstrates an inverse relationship between dosing frequency and medication adherence in various chronic diseases, with once-daily dosing resulting in the highest adherence rates. Reducing the dosing frequency may positively impact both clinical and patient-reported outcomes, as well as health care costs. However, the increased costs of less frequently administered drugs must be outweighed by the net savings achieved through improved adherence rates and better health outcomes. If trends among patients with chronic diseases apply, once-daily dosing regimens may improve adherence rates by approximately 6% to 14% among renal transplant patients and could substantially reduce the number of acute rejection episodes and graft failures, although the exact economic impact is difficult to estimate. Further research into adherence issues in transplant patients and the potential clinical and economic benefits of once-daily dosing of immunosuppressants is warranted.     

Symptom experience after lung transplantation: impact on quality of life and adherence

BACKGROUND: Patients' perceptions of immunosuppression- related symptom experience may impact on quality of life (QoL) and medication adherence. METHODS: A total of 308 lung transplant recipients were screened for study inclusion. Two hundred eighty-seven patients (response rate 93%) completed a 91-item questionnaire consisting of subscales focusing on symptom experiences (frequency and distress), and adherence. QoL was assessed by a 40-item standardized instrument. Impact of symptom experiences on QoL and adherence were assessed. Potential determinants of immunosuppression induced symptom experiences were evaluated. RESULTS: The most frequent reported symptoms were tremor (70%) and hirsutism (68.1%), whereas Cushingoid appearance (38.6%) and muscle weakness (31.9%) appeared to be the most distressing symptoms. Women (p < 0.001) and younger patients (<40 yr; p < 0.0001) reported a significantly higher level of symptom experience compared with their counterparts respectively. Symptom experiences negatively influenced QoL in all dimensions (p < 0.006). Those who described experiencing adverse effects reported significantly more "drug holidays" (p < or = 0.004) compared with those reporting minor frequent adverse effects. Patients' self-reported strategies to reduce adverse effects were to postpone medication intake (30%), to drop doses (8%), or to reduce doses (9%). CONCLUSIONS: This study establishes a relationship between patients' perceptions of immunosuppression-related symptom experiences and the impact on QoL and adherence. Immunosuppression is accompanied by significant adverse effects in both symptom frequency and distress. Most frequently experienced symptoms do not necessarily have the greatest impact on perceived distress, and vice versa. High levels of adverse effects tend to negatively influence patients' QoL and adherence. Future research is required to understand the relationship of these complex variables.     

肝移植受者服药依从性现状及其影响因素分析

目的:对肝移植受者服药依从性现状及其影响因素进行观察。方法:组建专人调查小组采用Mofisky-Green测评表对37例接受肝移植手术的患者进行随访调查,并对调查结果与可能的影响因素进行统计分析。结果:37例患者中,依从性不佳者29例(78.38%),依从性良好者8例(21.62%);在肝移植受者服药依从性具有差异性的影响因素中,年龄、文化程度、职业、居住地、术后服药时间、服药次数、对药物了解程度、是否定期复诊为保护因素(OR1),是否担心不良反应为危险因素(OR1)。结论:肝移植受者服药依从性现状不容乐观,应着重开展对肝移植患者关于疾病、药物、不良反应及其应对方法的教育工作,提高受者的自我护理意识,进而达到改善其服药依从性现状的目的。     

Improving medication adherence and outcomes in adult kidney transplant patients using a personal systems approach: SystemCHANGE™ results of the MAGIC randomized clinical trial

This study determined if a SystemCHANGE? intervention was more efficacious than attention control in increasing immunosuppressive medication adherence and improving outcomes in adult kidney transplant recipients during a 6‐month intervention phase and subsequent 6‐month (no intervention) maintenance phase. The SystemCHANGE? intervention taught patients to use person‐level quality improvement strategies to link adherence to established daily routines, environmental cues, and supportive people. Eighty‐nine patients (average age 51.8 years, 58% male, 61% African American) completed the 6‐month intervention phase. Using an intent‐to‐treat analysis, at 6 months, medication adherence for SystemCHANGE? (median 0.91, IQR 0.76‐0.96) and attention control (median 0.67, IQR 0.52‐0.72) patients differed markedly (difference in medians 0.24, 95% CI 0.13‐0.30, P < .001). At the conclusion of the subsequent 6‐month maintenance phase, the gap between medication adherence for SystemCHANGE? (median 0.77, IQR 0.56‐0.94) and attention control (median 0.60, IQR 0.44‐0.73) patients remained large (difference in medians 0.17, 95% CI 0.06‐0.33, P = .004). SystemCHANGE? patients evidenced lower mean creatinine and BUN at 12 months and more infections at 6 and 12 months. This first fully powered RCT testing SystemCHANGE? to improve and maintain medication adherence in kidney transplant recipients demonstrated large, clinically meaningful improvements in medication adherence. Clinical Trial Registration: NCT02416479.     

Evaluation of adherence and tolerability of prolonged‐release tacrolimus (Advagraf™) in kidney transplant patients in Germany: A multicenter,noninterventional study

This study assessed adherence to prolonged‐release tacrolimus (PR‐T)‐based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR‐T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4) months. Composite primary endpoint: nonadherence at V4, defined as self‐reported nonadherence on the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS^©), investigator‐rated nonadherence, and/or V4 tacrolimus trough level outside a predefined range. Secondary endpoints: individual BAASIS items, incidence of rejection, kidney function, and safety. Overall, 153 adult kidney recipients (mean [standard deviation] time post‐transplant 5.8 [4.6] years) were included. Nonadherence was high at V4 (67.7% [95% confidence interval 58.9%, 75.6%]). Medication‐taking adherence was 86.9% and 91.3% at V1 and V4, respectively; adherence to timing of medication intake was 58.2% and 58.3%, with little evidence of missed doses/drug holidays. Investigators rated adherence “good” in 85.6% of patients (V4). Two (1.3%) patients had acute rejection episodes. Kidney function remained stable (mean creatinine clearance, V1: 62.1 mL/min; V4: 65.3 mL/min). Investigators rated effectiveness of PR‐T as “very good”/“good” in 91.5% of patients. Most patients (94.7%) found PR‐T dosing more convenient than immediate‐release tacrolimus. PR‐T was well tolerated with high medication persistence.     

Non‐adherence to immunosuppressive medication in renal transplant recipients within the scope of the integrative model of behavioral prediction: a cross‐sectional study

Schmid‐Mohler G, Pechula Thut M, Wüthrich RP, Denhaerynck K, De Geest S. Non‐adherence to immunosuppressive medication in renal transplant recipients within the scope of the integrative model of behavioral prediction: a cross‐sectional study.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01056.x
© 2009 John Wiley & Sons A/S. Abstract: Background: Non‐adherence to immunosuppressive medication is strongly associated with poor outcomes. Identifying the factors influencing it is a first step in developing adherence interventions. This study’s objective was to investigate the prevalence of self‐reported and collaterally‐reported non‐adherence to immunosuppressives, and, based on the Integrative Model of Behavioral Prediction, to explore the association between non‐adherence, intention to adhere, attitudes, norms and self‐efficacy. Methods: This cross‐sectional study included a convenience sample of 114 renal transplant recipients in follow‐up care, one to five yr post‐transplant. Non‐adherence was measured by self‐reports and collateral reports. Factors of the Integrative Model of Behavioral Prediction were assessed using a self‐report questionnaire. Results: Self‐reports showed non‐adherence of 23.7%; collateral reports showed 3.8%; and a combination of the two showed 26.4%. Logistic regression analysis showed that the attitude “Not all immunosuppressive drugs are necessary to prevent rejection” was less frequent in patients with higher intentions to adhere, with an odds ratio (OR) of 0.05 (95% CI 0.01–0.50). The barrier of “Forgetfulness/Interruption of daily routine” was associated with non‐adherence, with an OR of 3.74 (95% CI 1.55–9.03). Conclusions: Forgetfulness is the most powerful barrier against adherence. Intention to adhere plays a minor role in non‐adherence in renal transplant recipients.     

Association between day of the week and medication adherence among adolescent and young adult kidney transplant recipients

Disruption of usual routines may hinder adherence, increasing the risk of rejection. We aimed to compare weekend versus weekday medication adherence among adolescent and young adult kidney transplant recipients, hypothesizing poorer adherence on weekends. We examined data from the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE‐IT). We assessed the 3‐month run‐in period (no intervention) and the 12‐month intervention interval, considering a potential interaction between weekend/weekday and treatment group. Adherence was monitored using electronic pillboxes in participants 11‐24 years followed in eight transplant centers in Canada and the United States. We used logistic regression with generalized estimating equations to estimate the association between weekends/weekdays and each of perfect taking (100% of prescribed doses taken) and timing (100% of prescribed doses taken on time) adherence. Taking (OR = 0.72 [95% CI 0.65‐0.79]) and timing (OR = 0.66 [95% CI 0.59‐0.74]) adherence were poorer on weekends than weekdays in the run‐in (136 participants) and the intervention interval (taking OR = 0.74 [0.67‐0.81] and timing OR = 0.71 [95% CI 0.65‐0.77]). There was no interaction by treatment group (64 intervention and 74 control participants). Weekends represent a disruption of regular routines, posing a threat to adherence. Patients and families should be encouraged to develop strategies to maintain adherence when routines are disrupted. TAKE‐IT registration number: Clinicaltrials.gov registration: NCT01356277 (May 17, 2011).     

Liver,simultaneous liver-kidney,and kidney transplantation from hepatitis C-positive donors in hepatitis C-negative recipients: A single-center study

Transplantation of organs from hepatitis C virus (HCV)-antibody (Ab) and -nucleic acid test (NAT) positive donors into HCV-negative recipients has been proposed to expand the donor pool and shorten waiting times. Data on early single-center outcomes are lacking. Nineteen liver (LT, including seven simultaneous liver-kidney [SLKT]) and 17 kidney transplant (KT) recipients received organs from HCV (+) donors; of these, 13 were HCV NAT (+) in each group. All patients who received organs from HCV NAT (+) donors developed HCV viremia post-transplant except for 2 KT recipients. Patients were treated with a variety of direct-acting antiviral regimens, with high rates of sustained virologic response among those with at least 12 weeks of follow-up past the end of treatment: 12/13 (92%) and 8/8 (100%) among LT/SLKT, and KT recipients. Median time to treatment start was 42 days (interquartile range [IQR] 35-118 days) and 40 days (IQR 26-73) post-LT/SLKT and KT, respectively. One death occurred in a SLKT recipient unrelated to HCV or its treatment. There was no significant increase in rejection, proteinuria, or changes in immunosuppression in any group. Organs from HCV-viremic donors can be utilized for HCV-uninfected recipients with good short-term outcomes.     

Race and electronically measured adherence to immunosuppressive medications after deceased donor renal transplantation

Nonadherence to immunosuppressive medications may partly explain the worse allograft outcomes among black recipients of renal transplants. In a prospective cohort study of recipients of deceased donor renal transplants, microelectronic cap monitors were placed on bottles of one immunosuppressive medication to (1) measure average daily percentage adherence during the first posttransplantation year and (2) determine the factors associated with adherence. A total of 278 transplant recipients who provided sufficient microelectronic adherence data were grouped into four categories of average daily percentage adherence: 95 to 100% adherence (41.0% of patients), 80 to 95% adherence (32.4%), 50 to 80% adherence (12.9%), and 0 to 50% adherence (13.7%). In the unadjusted ordinal logistic regression model, black race was associated with decreased adherence (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.26 to 0.72; P = 0.001). Cause of renal disease, Powerful Others health locus of control, transplant center, and dosing frequency were also associated with adherence. After adjustment for transplant center and dosing frequency, the association between black race and decreased adherence was substantially attenuated (OR, 0.65; 95% CI, 0.38 to 1.14, P = 0.13). Transplant center (P = 0.003) and increased dosing frequency (OR, 0.43; 95% CI, 0.22 to 0.86, for three or four times per day dosing; OR, 2.35; 95% CI, 1.01 to 5.45, for daily dosing; versus two times per day dosing; P = 0.003) remained independently associated with adherence. Other baseline demographic, socioeconomic, medical, surgical, and psychosocial characteristics were not associated with adherence. The transplant center and dosing frequencies of immunosuppressive medications are associated with adherence and explain a substantial proportion of the race-adherence relationship.     

Report from the American Society of Transplantation Psychosocial Community of Practice Adherence Task Force: Real‐world options for promoting adherence in adult recipients

Starting in 2015, the American Society of Transplantation Psychosocial Community of Practice, with representatives of the Transplant Pharmacy Community of Practice, convened a taskforce to develop a white paper that focused on clinically practical, evidenced‐based interventions that transplant centers could implement to increase adherence to medication and behavioral recommendations in adult solid organ transplant recipients. The group focused on what centers could do in their daily routines to implement best practices to increase adherence in adult transplant recipients. We developed a list of strategies using available resources, clinically feasible methods of screening and tracking adherence, and activities that ultimately empower patients to improve their own self‐management. We limited the target population to adults because they predominate the research, and because adherence issues differ in pediatric patients, given the necessary involvement of parents/guardians. We also examined broader multilevel areas for intervention including provider and transplant program practices. Ultimately, the task force aims to foster greater recognition, discussion, and solutions required for implementing practical interventions targeted at improving adherence.