Gerda Drent

The Psychometric Properties and Practicability of Self-Report Instruments to Identify Medication Nonadherence in Adult Transplant Patients: A Systematic Review

Introduction. Nonadherence to immunosuppressive therapy is recognized as a key prognostic indicator for poor posttransplantation long-term outcomes. Several methods aiming to measure medication nonadherence have been suggested in the literature. Although combining measurement methods is regarded as the gold standard for measuring nonadherence, self-report is generally considered a central component of adherence assessment. However, no systematic review currently exists to determine which instrument(s) are most appropriate for use in transplant populations. Methodology. The transplant360 Task Force first performed a survey of the self-report adherence instruments currently used in European centers. Next, a systematic literature review of self-report instruments assessing medication adherence in chronically ill patients was conducted. Self-report instruments were evaluated to assess those which were: (a) short and easy to score; (b) assessed both the taking and timing of medication intake; and (c) had established reliability and validity. Results. Fourteen instruments were identified from our survey of European centers, of which the Basel Assessment of Adherence Scale for Immunosuppressives met the aforementioned criteria. The systematic review found 20 self-report instruments, of which only two qualified for use in transplantation, that is, the Brief Antiretroviral Adherence Index and the Medication Adherence Self-Report Inventory. Discussion. The three selected self-report scales may assist transplant professionals in detecting nonadherence. However, these scales were only validated in patients with HIV. Although HIV shares similar characteristics with transplantation, including the importance of taking and timing of medication, further validation in transplant populations is required.

Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol

After orthotopic liver transplantation (OLT) bone mass rapidly declines and vertebral fracture rate increases. We studied bone loss and parameters of bone turnover in 53 consecutive patients. In an attempt to reduce bone loss the patients were prophylactically treated with cyclical etidronate in addition to daily 1α-hydroxyvitamin D3 and calcium. During the first 3 months after transplantation median lumbar spinal bone mineral density (BMD) decreased 4.5%; subsequently no significant changes occurred. Median hip BMD continued to fall during the first post-transplantation year and deteriorated 7% over the whole study period. New vertebral fractures were seen in 25% of the patients, which is not lower than previously reported rates in patients not receiving cyclical etidronate. Parathyroid hormone levels increased after OLT (p=0.01), but remained within normal ranges. Urinary hydroxyproline levels were increased and normalized in the second half-year after OLT. Elevated fasting calciuria increased further after OLT. 1,25-Dihydroxy-vitamin D3 levels were lowered pre-OLT (25 vs 66 pmol/1,p<0.001) and normalized at 3 months after OLT. Serum osteocalcin concentrations remained unchanged and were reduced compared with levels in healthy controls. In summary, increased bone resorption occurs after OLT with persistent decreased bone formation, leading to vertebral fracture in 25% of patients. Etidronate, 1α-calcidol and calcium treatment did not prevent bone loss.

Prevalence of prednisolone (non)compliance in adult liver transplant recipients

Limited evidence is available concerning (non)compliance with the immunosuppressive regimen in adult liver transplant recipients. In our study we prospectively assessed prednisolone (non)compliance in 108 adult liver transplant recipients using electronic event monitoring (EEM) in an outpatient setting. The EEM is a pill bottle fitted with a cap containing a microelectronic circuit that registers date and time of bottle openings and closings. Median taking compliance was 100% (range 60–105%), median dosing compliance was 99% (range 58–100%); median timing compliance (TIC) was 94% (42–100%). A drug holiday (DH) of ≥48 h was found in 39% of the patients of ≥72 h in 16% of the patients. Using EEM in liver transplant recipients, we found an overall high level of compliance for prednisolone, except that TIC was low in about one third of the patients. Age below 40 years was found a significant risk factor for decreased TIC and for DHs of ≥48 h.

Symptom experience associated with immunosuppressive drugs after liver transplantation in adults: possible relationship with medication non-compliance?

Abstract:  Symptom experience (occurrence and perceived distress) associated with side effects of immunosuppressive medications in organ transplant patients may well be associated with poorer quality of life and medication non‐compliance. The aims of this study were: first, to assess symptom experience in clinically stable adult patients during long‐term follow‐up after liver transplantation; and second, to study the relationship between symptom experience and medication non‐compliance. This cross‐sectional study included 123 liver transplant patients. Symptom experience was assessed using the “Modified Transplant Symptom Occurrence and Symptom Distress Scale” (29‐item version) at the annual evaluation. According to the duration of follow‐up, patients were divided into a short‐term (1–4 yr) and a long‐term (5–18 yr) cohort. Medication non‐compliance was measured using electronic monitoring. Results showed that increased hair growth was the most frequent symptom in both sexes. Symptom distress was more serious in women than in men. The most distressing symptom in women was excessive and/or painful periods, while in men this was impotence. Clear differences were revealed at item level between symptom occurrence and symptom distress in relationship with the two time cohorts and between sexes. No relationship was found between symptom experience and prednisolone non‐compliance.

Weight gain, overweight and obesity in solid organ transplantation—a study protocol for a systematic literature review

BackgroundOverweight and obesity, which have a substantial impact on health in the general population, have similar prevalence in solid organ transplant recipients but carry even more serious ramifications. As this group’s use of immunosuppressive medication increases the risk for comorbidities, e.g. metabolic syndrome and cardiovascular disease, the prevention of additional risk factors is vital. This systematic review will be the first to summarize the issue of weight gain, overweight and obesity concurrently within and across solid organ transplantation. The three research questions relating to solid organ transplantation are the following: (1) What are the prevalence and evolution of overweight and obesity from pre- to post-transplant?; (2) Which pre- and post-transplant risk factors are associated with post-transplant weight gain, overweight or obesity? and (3) Which post-transplant patient outcomes and comorbidities are associated with pre- and post-transplant weight gain, overweight and obesity?Methods/DesignMEDLINE via PubMed, The Cochrane Library, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO and Excerpta Medica DataBase (EMBASE) will be searched for original quantitative studies in adult liver, heart, lung or kidney transplant patients. Topics of interest will be the prevalence and evolution of overweight and obesity over time, risk factors associated with changes in weight or body mass index (BMI), overweight and obesity, and the relationship of weight or BMI with post-transplant outcomes and comorbidities. Screening of titles and abstracts, full-text reading and data extraction will be divided between three researchers. Researchers will cross-check one another’s screening decisions for random samples of studies to adhere as closely as possible to the recommendations of The Cochrane Collaboration. For quality assessment, a purpose-adapted 19-item instrument will be used. Effect sizes will be calculated for relationships investigated in a minimum of five studies. Random effects meta-analysis with moderator analyses will be conducted if applicable.DiscussionThis systematic review will comprehensively synthesize the existing evidence concerning weight gain, overweight and obesity in solid organ transplantation in view of magnitude, influencing factors and associations with patient outcomes and comorbidities. The results can fuel the development of interventions to prevent weight gain in the solid organ transplant population.Systematic review registrationPROSPERO CRD42014009151

Quality of life in patients with familial amyloidotic polyneuropathy long-term after liver transplantation

Liver transplantation aims to halt the progression of the disease in patients with familial amyloidotic polyneuropathy (FAP) caused by hereditary transthyretin-related (ATTR) amyloidosis. Insight in health-related quality of life of these transplanted FAP-patients can be of help to optimize health care delivery. The aim of this cross-sectional study was to assess the health-related quality of life of patients with FAP long-term after transplantation. Nine patients with a post-transplant follow-up of 4 years or more were included in the study. During the annual checks, health-related quality of life was measured with the Short Form-36 (SF-36). Data were compared with non-FAP transplanted patients with the same duration of follow-up and with the normal Dutch population. Pre-transplant, all patients had signs of mild to moderate peripheral polyneuropathy. The results showed that in patients with FAP health-related quality of life was stable in the first 4 years after transplantation. The domain of physical well-being at 4 years after transplantation was significantly lower compared to non-FAP transplanted patients and control Dutch population. The domain of emotional well-being was comparable with non-FAP controls. However, on most health areas patients with FAP scored lower than the non-FAP transplanted patients and the Dutch controls. After four years, the three patients with FAP with longest follow-up (9–12 years) deteriorated in all health domains, except in self-perceived mental health. This study, including only a small number of patients with FAP, shows a relatively low health-related quality of life after liver transplantation, which may deteriorate further with longer follow-up.

Prednisolone noncompliance and outcome in liver transplant recipients

Recently, we reported on the prevalence of prednisolone noncompliance in liver transplant recipients as measured by electronic monitoring [1]. In the group of 108 adult patients, a median of 4 years after transplantation, the median taking compliance was 100% (range: 60–105), median dosing compliance was 99% (range: 58–100), and median timing compliance was 94% (range: 42–100). A drug holiday of ‡48 h was found in 39% of the patients, of ‡72 h in 16% of the patients. After 2 years of followup, we now report on the possible influence of the measured noncompliance on clinical outcome. The following parameters of outcome were studied: liver tests as determined at baseline, and 1 and 2 years later; biopsy proven episodes of acute rejection for which treatment was needed; change in dosages of immunosuppression; hospital re-admissions, and patient and graft survival. Only one patient experienced an episode of rejection; 19% of patients achieved a substantial decrease of immunosuppression after 2 years; 19% of patients were hospitalized for several reasons; one patient died and another one received a second transplant. Except for a somewhat higher alkaline phosphatase (APh) in patients who showed the lowest level of compliance, we found no relations between the compliance parameters and outcome. Using rank correlation, at baseline a weak negative correlation was found between APh and taking compliance (P 1⁄4 0.024, r 1⁄4 )0.216), and between APh and dosing compliance (P 1⁄4 0.014, r 1⁄4 )0.236). A positive correlation was found at baseline between APh and drug holidays of ‡48 h (P 1⁄4 0.033, r 1⁄4 0.206). At 2 years of follow-up, APh was negatively correlated with dosing compliance (P 1⁄4 0.049, r 1⁄4 )0.192). See Fig. 1 for illustration. From the present study, it may be concluded that the level of prednisolone noncompliance of our liver

Trajectories of anxiety and depression after liver transplantation as related to outcomes during 2-year follow-up: a prospective cohort study

Objective The aims of the study were to examine whether distinct trajectories of anxious and depressive symptoms are present among liver transplant recipients from before transplantation to 2 years afterward, to identify associated demographic, clinical, and individual characteristics, and to examine the influence of distinct trajectories on outcomes. Methods A prospective, multicenter cohort study was performed among 153 liver transplant recipients. Data were retrieved using questionnaires administered before transplantation and at 3, 6, 12, and 24 months after transplantation. Clinical data were retrieved by medical record review. Latent class growth analysis was used to identify distinct trajectories. &khgr;2 test, analyses of variance, and multinomial logistic regression were used to identify associated variables and the impact of the distinct trajectories on outcomes. Results Three distinct trajectories for symptoms of anxiety (State-Trait Anxiety Inventory-short form) as well as depression (Center for Epidemiological Studies Depression Scale) were identified: “no symptoms,” “resolved symptoms,” and “persistent symptoms.” The trajectories of persistent anxiety and depression comprised, respectively, 23% and 29% of the transplant recipients. Several clinical and individual variables were associated with the trajectories of persistent anxiety and/or depression: experiencing more adverse effects of the immunosuppressive medication, lower level of personal control, more use of emotion-focused coping, less disclosure about the transplant, and more stressful life events. The trajectories of persistent symptoms were associated with worse outcomes regarding medication adherence and health-related quality of life, but not with mortality. Conclusions A significant subset of transplant recipients showed persistent symptoms of anxiety and depression from before to 2 years after transplantation. These results emphasize the importance of psychosocial care in the transplant population.

A prospective cohort study on posttraumatic stress disorder in liver transplantation recipients before and after transplantation: Prevalence, symptom occurrence, and intrusive memories

OBJECTIVE This study aimed at increasing the understanding of posttraumatic stress disorder (PTSD) in liver transplant patients by describing the course of PTSD, symptom occurrence, psychological co-morbidity, and the nature of re-experiencing symptoms. METHODS A prospective cohort study was performed among 95 liver transplant recipients from before transplantation up until one year post-transplantation. Respondents filled out a questionnaire regarding psychological functioning (PTSD, anxiety, and depression) before, and at 3, 6, and 12months post-transplantation. Both quantitative and qualitative methods were used to analyze the data. RESULTS Before transplantation, respectively 10.5% and 6.3% of the respondents were identified as possible cases of full or partial PTSD. In all cases, co-morbid conditions of anxiety and/or depression were present. After transplantation, no new onset of full PTSD was found. New onset of possible partial PTSD was found in six respondents. Arousal symptoms were the most frequently reported symptoms, but may not be distinctive for PTSD in transplant patients because of the overlap with disease- and treatment-related symptoms. Re-experiencing symptoms before transplantation were mostly related to waiting for a donor organ and the upcoming surgery; after transplantation this was related to aspects of the hospital stay. CONCLUSIONS In our group of liver transplant patients, PTSD symptomatology was more present before transplantation than after transplantation. Being diagnosed with a life-threatening disease seemed to be the main stressor. However, when a diagnosis of PTSD is suspected, assessment by a clinician is warranted because of the overlap with mood and anxiety disorders, and disease- and treatment-related symptoms.

Correlates and outcomes of alcohol use after single solid organ transplantation: a systematic review and meta-analysis

BACKGROUND Reviews on alcohol use in transplant recipients focus on liver recipients and their risk of post-transplant rejection, but do not assess alcohol use in kidney, heart, or lung transplant recipients. This systematic review and meta-analysis aims to synthesize the evidence on correlates and outcomes of any alcohol use and at-risk drinking after solid organ transplantation (Tx). METHODS We searched 4 databases for quantitative studies in adult heart, liver, kidney and lung Tx recipients, investigating associations between post-Tx alcohol use and correlates and/or clinical, economic or quality of life outcomes. Paper selection, data extraction and quality assessment were performed by 2 reviewers independently. A pooled odds ratio (OR) was computed for each correlate/outcome reported ≥5 times. RESULTS Of the 5331 studies identified, 76 were included in this systematic review (93.3% on liver Tx; mean sample size 148.9 (SD = 160.2); 71.9% male; mean age 48.9 years (SD = 6.5); mean time post-Tx 57.7 months (SD = 23.1)). On average, 23.6% of patients studied used alcohol post-transplant. Ninety-three correlates of any post-Tx alcohol use were identified, and 9 of the 19 pooled ORs were significantly associated with a higher odds for any post-Tx alcohol use: male gender, being employed post-transplant, smoking pre-transplant, smoking post-transplant, a history of illicit drug use, having first-degree relatives who have alcohol-related problems, sobriety <6 months prior to transplant, a history of psychiatric illness, and having received treatment for alcohol-related problems pre-transplant. On average 15.1% of patients had at-risk drinking. A pooled OR was calculated for 6 of the 47 correlates of post-Tx at risk drinking investigated, of which pre-transplant smoking was the only correlate being significantly associated with this behavior. None of the outcomes investigated were significantly associated with any use or at-risk drinking. CONCLUSION Correlates of alcohol use remain under-investigated in solid organ transplant recipients other than liver transplantation. Further research is needed to determine whether any alcohol use or at-risk drinking is associated with poorer post-transplant outcomes. Our meta-analysis highlights avenues for future research of higher methodological quality and improved clinical care. PROTOCOL REGISTRATION PROSPERO protocol CRD42015003333.