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.     

Psychiatric differences between liver transplant candidates with familial amyloid polyneuropathy and those with alcoholic liver disease

BACKGROUND: Psychiatric diagnoses are very common in liver transplant candidates, and such diagnoses are predictive of a poor clinical evolution and quality of life after transplantation. Also, nonadherence before the transplant is predictive of nonadherence after the transplant. METHODS: We studied the psychiatric and psychosocial profiles of 85 liver transplant candidates, comprising consecutive patients attending outpatient clinics of a liver transplantation unit at a public hospital. Interviews and questionnaires were used to measure personality traits, symptoms of anxiety and depression, social support, and adherence. These patients were broken into 3 groups: patients with familial amyloid polyneuropathy (n = 20), patients with alcoholic liver disease (n = 33), and patients with other liver diseases (n = 32). RESULTS: About 58% of patients had a current psychiatric diagnosis (24.8%, major depressive disorder, 22.3% generalized anxiety disorder, 8.3% adaptive disorder, 2.3% abuse of or dependence on substances other than alcohol). Current psychiatric diagnosis did not differ between patients with familial amyloid polyneuropathy and patients with alcoholic liver disease. Patients with alcoholic liver disease showed lower scores for 2 protective personality traits, social support and adherence to medication, than other patients. Patients with familial amyloid polyneuropathy showed higher scores for those traits. CONCLUSIONS: All patients waiting for a liver transplant should undergo psychiatric and psychological assessment. Some psychological characteristics such as personality traits and social support differ between clinical groups, so it may be useful to design different approaches for each group. Patients with alcoholic liver disease may require a special approach to improve adherence to medication.     

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.     

Psychological Functioning, Nonadherence and Health Outcomes After Pediatric Liver Transplantation

The present study empirically assessed the relationships between adherence behaviors and HRQOL, parent and child psychological functioning and family functioning, and investigated the relationship between adherence behaviors and health outcomes in children who were within 5 years of their liver transplantation. Participants included 38 children (mean = 8.5 years, range 28 months to 16 years) and their parent/guardian(s). HRQOL and psychological functioning were examined using well-validated assessment measures. Measures of adherence included the rate of clinic attendance and standard deviations (SDs) of consecutive tacrolimus blood levels, which were collected and evaluated retrospectively. Measures of child health status included the frequency of hospital admissions, liver biopsies, episodes of rejection and graft function for the year prior to study participation. Results indicated that nonadherence was related to lower physical HRQOL, more limitations in social and school activities related to emotional and behavioral problems, parental emotional distress and decreased family cohesion. Nonadherence was also related to frequency and duration of hospitalizations, liver biopsies and rejection episodes. These results suggest that empirically based assessment of HRQOL, parenting stress and family functioning may help identify patients at risk for nonadherence, and may allow for the need-based delivery of appropriate clinical interventions.     

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。     

The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi‐Site Study

Nonadherence to immunosuppressant medications is a leading cause of poor long‐term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk‐stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi‐site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1–17‐year‐old) liver transplant recipients were enrolled and followed for 2 years. The a‐priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre‐adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty‐three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.     

Corticosteroids and concomitant medication in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation

Abstract The steroid-paring effect and the use of concomitant medication during the treatment of liver transplant patients with the novel immunosuppressant FK 506 were evaluated within the European multicentre, randomized, parallel-group study in liver transplantation. Patients undergoing primary liver transplantation were randomized to treatment with FK 506 ( n = 267) or with a cyclosporin-based immunosuppressive regimen ( n = 273). The total cumulative steroid usage was significantly reduced in the FK 506 treatment group, which is likely to have resulted from the lower incidence of acute rejection in these patients. The number of patients receiving antidiabetic, diuretic and antihypertensive therapy did not differ between the two treatment groups, even though the incidence of diabetes mellitus and oliguria was significantly higher in the FK 506 group. It can, therefore, be assumed that in a number of such cases the severity of these events was very mild necessitating no specific therapy.     

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.     

肝移植免疫抑制治疗临床应用进展

自从开展器官移植以来,外科手术技术和免疫抑制治疗发生了巨大变化。在过去十年中,排斥反应和移植物失功发生率已明显下降。目前,应用免疫抑制剂的长期并发症已取代排斥反应成为移植治疗的主要挑战。与肾移植和心脏移植相比,肝移植术后急性排斥反应发生率并不高,并且对移植物存活的影响较小,但不合理使用免疫抑制剂也会导致移植失败。如何诱导产生稳定而持久的免疫耐受,适当的免疫调节治疗将是肝移植良好开展的主要保证。本文拟对免疫抑制剂的种类、应用情况和目前的治疗进展进行综述,并探讨肝移植免疫抑制治疗的前景。     

Compliance and late acute rejection after kidney transplantation: a psycho-medical perspective

INTRODUCTION: We examined the relationship between late acute rejection (LAR) after cadaveric kidney transplantation and medical compliance utilizing a modified version of the Long-term Medication Behaviour Self-efficacy Scale (LTMBS-scale), a validated patient self-report questionnaire. The original LTMBS-scale uses a five-point scale, however, our pilot study showed that patients found it difficult to discriminate between the five options. We therefore modified this to a three-point scale. PATIENTS AND METHODS: We carried out a retrospective analysis of all patients who received a kidney transplant in our unit in the cyclosporin (CyA) era. We divided rejections into early and late rejection based on the time interval after transplantation. Graft rejection was confirmed by biopsy; LAR was defined as acute rejection occurring after 90 d. We retrospectively administered the modified LTMBS-scale to determine individual patient confidence and self-efficacy in taking their medications in a variety of situations (home, work, leisure, psychological and physical). Individual patient confidence and self-efficacy was analysed in relationship to compliance behaviour. RESULTS: Twenty-four questionnaires were distributed, 22 (92%) were returned fully completed. The overall results suggested that our patients surveyed were not particularly confident (mean score 2.17 out of maximum possible 3) in taking their medications in a variety of contexts. They demonstrated significantly less confidence (mean score 1.0) when experiencing physical (brittle bones, feeling 'ill') and psychological ('sadness') side-effects of medication and emotional reactions to the experience of chronic illness. CONCLUSION: Negative physical and psychological states were related to low self-efficacy with the taking of immunosuppressive medication, non-compliance and subsequent LAR in our cohort of patients.     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为“免疫特惠器官”,肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

Immunosuppressant treatment adherence, barriers to adherence and quality of life in renal and liver transplant recipients in Spain

To assess the adherence to immunosuppressant therapy (IST) and perceived barriers affecting IST adherence and quality of life (QOL) in patients who had received a renal (RT) or liver transplant (LT), a questionnaire was sent to over 9000 RT and LT recipients in Spain. Questionnaire comprised questions about patient's socio-demographic, organ transplant and medication characteristics; IST adherence and patient's perceived barriers to adherence; and patient's QOL using the EuroQol. Data from 1983 RT patients and 1479 LT patients were analyzed. Self-reported adherence to IST in RT (92.6%) and LT (88.5%) recipients was high. Daily medication intake (mean of 2-3 doses/d per patient) was considered a lifestyle restriction in about 25% of transplant recipients and was the most common barrier to adherence perceived by over 30% of RT and LT patients. Overall, high-intensity treatment regimens were associated with poorer QOL (EuroQol <70) compared with low-intensity treatment regimens. Most RT (71.0%) and LT (61.4%) patients would prefer to suppress the evening dose if they were able to. Although high adherence rates to IST were reported in this first large Spanish survey in RT and LT patients, adjustment of daily treatment intensity by less frequent dosing may be an adequate strategy to minimize barriers to adherence and improve QOL.     

Couples After Renal Transplantation: Impact of Sex and Relationship Quality on Adherence in a Prospective Study

BackgroundIn patients after kidney transplantation, nonadherence to immunosuppressant medication is a common problem. Identifying factors that influence adherence could optimize medical care and prevent nonadherence. Kidney transplantation is a stressful situation for the patient and also for the relatives. The recipients of renal transplants as well as the family system have to be taken into account as potential impact factors.MethodsFifty-six couples with a renal transplant recipient were investigated regarding adherence, relationship satisfaction, social support, and quality of life. Moreover, sex and role differences (patient vs partner) as well as differences within the couple were analyzed. Impact factors on adherence were identified.ResultsFemale recipients of renal transplant reported higher relationship satisfaction than male recipients, female spouses, and male spouses. Physical quality of life was lower in renal transplant recipients compared with caregivers. For male renal transplant recipients, significant predictors of adherence, such as social support, relationship quality, and quality of life emerged, whereas for female renal transplant recipients mental quality of life and education level were found to influence adherence.ConclusionsThe study reveals the importance of relationship functioning of couples after kidney transplantation, as well as considering sex and role differences. There is a need to examine the posttransplantation nonadherence risk profile of women and men separately.     

Tailoring immunosuppressants to hepatitis C virus–infected transplant patients

Hepatitis C virus (HCV) is the leading indication for liver transplant in the world. After transplantation, patients remain infected with HCV and are at high risk for recurrent end-stage liver disease. We will review retrospective and prospective studies, which suggest that specific immunosuppressive cocktails are more associated with severe recurrent HCV and relate these studies to in vitro analysis of the effect of immunosuppressants on HCV in vitro. Immunosuppressive antibodies and high-dose steroids have been associated with increased viral replication in the short term, and data also suggest worsening liver disease in the long term. On the other hand, mycophenolate mofetil, azathioprine, and cyclosporine have all been shown to have antiviral properties against HCV in in vitro studies. Although future research is desperately needed, a picture of how the risks and benefits of immunosuppressive regimens in HCV-infected patients differ from non–HCV-infected patients is emerging, and possible recipes for immunosuppressant cocktails tailored to limit HCV while still preventing graft rejection are contemplated.     

RhD阴性患者接受RhD阳性供肝移植

目的 探讨RhD阴性患者肝移植时的供肝选择、输血方法和术后免疫抑制方案.方法 回顾分析1例RhD阴性O型肝癌患者接受RhD阳性O型供肝的病例资料并复习相关文献.该患者术中输RhD阴性O型红细胞5U、RhD阳性O型血浆3000ml和冷沉淀30 U.术后应用他克莫司十甲基强的松龙免疫抑制方案,1个月后停用甲基强的松龙.结果 该患者术后未发生排斥反应和溶血反应,肝功能恢复顺利.术后未检测抗-D抗体.术后9个月肝癌复发,13个月死于肝癌脑转移.结论 RhD阴性患者可以接受RhD阳性供肝,疗效满意.术中和术后如需输血,可根据患者有或无抗-D抗体选择输RhD阴性或阳性红细胞和血小板,输血浆和冷沉淀则不受RhD血型限制.术后不用特别加强免疫抑制方案.     

Impact of stress, distress and feelings of indebtedness on adherence to immunosuppressants following kidney transplantation

In order to ensure transplantation's long-term success, transplant recipients need to comply with a strict regimen of immunosuppressant medication on a daily basis for the rest of their lives. Nonadherence is one of the major causes of organ rejection. Because compliance is voluntary, it is likely to be influenced by an individual's beliefs and feelings. This study examined the impact on compliance of the following factors: (1) transplant-related stress; (2) general perceived stress; (3) psychosocial distress and (4) feelings of indebtedness and guilt towards the donor. Fifty kidney recipients (34 men, 16 women) filled out self-report questionnaires. The results indicate that 46% acknowledged sub-optimal compliance in the last month; patients more often reported not taking the medication exactly as prescribed than forgetting to take it. The results also suggest that psychological distress and general perceived stress affect compliance negatively, whereas feelings of indebtedness improve it. These results have implications for the understanding and management of compliance following organ transplantation.     

Is social support associated with post-transplant medication adherence and outcomes? A systematic review and meta-analysis

Although social support is used to determine transplant eligibility, the relationship between social support, medication adherence, and survival among transplant recipients remains unclear. We estimated the relationship between social support and post-transplant medication adherence and outcomes using 10 electronic databases from inception to January 2016. Study quality was assessed and all review stages were conducted independently by 2 reviewers. Systematic review and meta-analysis were conducted. Thirty-two studies (9102 participants) met inclusion criteria: 21 assessed medication adherence (5197 participants), and 13 assessed clinical outcomes (3905 participants). Among high quality studies, neither social support nor marital status was predictive of medication adherence or post-transplant outcomes. Social support was not associated with medication adherence. It was associated with superior post-transplant outcomes, but the relationship was not significant among high quality studies. Compared to unmarried recipients, married recipients were more likely to adhere to medication post-transplant, but this relationship was not significant among high quality studies. Marital status was not significantly associated with transplant success. Social support is weakly and inconsistently associated with post-transplant adherence and outcomes. Larger prospective studies using consistent and validated measures are needed to justify the use of inadequate social support as a contraindication to transplantation.