Health-related quality of life and psychological indicators of thriving 15-19 years after heart or lung transplantation.

BACKGROUND: Survival into the second decade after cardiothoracic transplantation (CTX) is no longer uncommon. Few data exist on any health-related quality of life (HRQOL) impairments survivors face, or whether they may even experience positive psychological outcomes indicative of "thriving" (e.g., personal growth). We provide such data in a long-term survivor cohort. METHODS: Among 304 patients prospectively studied across the first 2 years post-CTX, we re-interviewed patients ≥15 years post-CTX. We (a) examined levels of HRQOL and positive psychological outcomes (posttraumatic growth related to CTX, purpose in life, life satisfaction) at follow-up, (b) evaluated change since transplant with mixed-effects models, and (c) identified psychosocial and clinical correlates of study outcomes with multivariable regression. RESULTS: Of 77 survivors, 64 (83%) were assessed (35 heart, 29 lung recipients; 15-19 years post-CTX). Physical HRQOL was poorer than the general population norm and earlier post-transplant levels (P's < .001). Mental HRQOL exceeded the norm (P < .001), with little temporal change (P = .070). Mean positive psychological outcome scores exceeded scales' midpoints at follow-up. Life satisfaction, assessed longitudinally, declined over time (P < .001) but remained similar to the norm at follow-up. Recent hospitalization and dyspnea increased patients' likelihood of poor physical HRQOL at follow-up (P's ≤ .022). Lower sense of mastery and poorer caregiver support lessened patients' likelihood of positive psychological outcomes (P's ≤ .049). Medical comorbidities and type of CTX were not associated with study outcomes at follow-up. CONCLUSIONS: Despite physical HRQOL impairment, long-term CTX survivors otherwise showed favorable outcomes. Clinical attention to correlates of HRQOL and positive psychological outcomes may help maximize survivors' well-being.

The Combined Roles of Race/Ethnicity and Substance Use in Predicting Likelihood of Kidney Transplantation.

BACKGROUND: Racial/ethnic minorities face known disparities in likelihood of kidney transplantation. These disparities may be exacerbated when coupled with ongoing substance use, a factor also reducing likelihood of transplantation. We examined whether race/ethnicity in combination with ongoing substance use predicted incidence of transplantation. METHODS: Patients were enrolled between March 2010 and October 2012 at the time of transplant evaluation. Substance use data were retrieved from transplant evaluations. Following descriptive analyses, the primary multivariable analyses evaluated whether, relative to the referent group (White patients with no substance use), racial/ethnic minority patients using any substances at the time of evaluation were less likely to receive transplants by the end of study follow-up (August 2020). RESULTS: Among 1152 patients, 69% were non-Hispanic White, 23% non-Hispanic Black, and 8% Other racial/ethnic minorities. White, Black, and Other patients differed in percentages of current tobacco smoking (15%, 26%, and 18%, respectively; P = 0.002) and illicit substance use (3%, 8%, and 9%; P < 0.001) but not heavy alcohol consumption (2%, 4%, and 1%; P = 0.346). Black and Other minority patients using substances were each less likely to receive transplants than the referent group (hazard ratios ≤0.45, P ≤ 0.021). Neither White patients using substances nor racial/ethnic minority nonusers differed from the referent group in transplant rates. Additional analyses indicated that these effects reflected differences in waitlisting rates; once waitlisted, study groups did not differ in transplant rates. CONCLUSIONS: The combination of minority race/ethnicity and substance use may lead to unique disparities in likelihood of transplantation. To facilitate equity, strategies should be considered to remove any barriers to referral for and receipt of substance use care in racial/ethnic minorities.

Promoting medication adherence from the perspective of adolescent and young adult kidney transplant recipients, parents, and health care professionals: A TAKE-IT TOO study.

Medication non-adherence is an important factor limiting allograft survival after kidney transplantation in AYA. Some interventions, including the TAKE-IT, showed some success in promoting adherence but the potential for scalability and use in routine clinical practice is limited. We applied user-centered design to gather the perspectives of recipients, parents, and health professionals concerning their needs, challenges, and potential intervention strategies to design an optimal, multi-component medication adherence intervention. The qualitative study was conducted at four Canadian and three American kidney transplant programs. Separate focus groups for recipients, parents, and health professionals were convened to explore these stakeholders' perspectives. Directed content analysis was employed to identify themes that were shared vs distinct across stakeholders. All stakeholder groups reported challenges related to taking medications on time in the midst of their busy schedules and the demands of transitioning toward independence during adolescence. The stakeholders also made suggestions for the multi-component behavioral intervention, including an expanded electronic pillbox and companion website, education materials, and customized digitized features to support shared responsibility and communication among recipients, parents, and health professionals. Several suggestions regarding the functionality and features of the potential intervention reported in this early stage will be explored in more depth as the iterative process unfolds. Our approach to actively involve all stakeholders in the process increases the likelihood of designing an adherence intervention that is truly user-informed and fit for the clinical setting.

Impact of a Mobile Health Intervention on Long-term Nonadherence After Lung Transplantation: Follow-up After a Randomized Controlled Trial.

BACKGROUND: In a randomized controlled trial, lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the end of the trial and evaluated other potential risk factors for long-term nonadherence. METHODS: Adherence in 8 areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups' nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics' associations with nonadherence. RESULTS: One hundred five LTRs (75% of survivors) were assessed (M = 3.9 years posttransplant, SD = 0.8). Nonadherence rates in the past month were 23%-81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%-23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (P < 0.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final randomized controlled trial assessment) were each associated with nonadherence in at least 1 area at follow-up (P < 0.05). CONCLUSIONS: Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions.

Posttransplant Medical Adherence: What Have We Learned and Can We Do Better?

PURPOSE OF REVIEW: Non-adherence to the medical regimen after kidney transplantation can contribute to poor clinical outcomes, and strategies to maximize adherence are sought by care providers and patients alike. We assessed recent evidence on prevalence, risk factors, and clinical outcomes associated with non-adherence to the medical regimen after kidney transplantation. We summarized recent clinical trials testing interventions to improve adherence and generated recommendations for future research and clinical practice. RECENT FINDINGS: A large evidence base documents rates of non-adherence to each of the multiple components of the regimen, including medication-taking, lifestyle activities, clinical care requirements, and substance use restrictions. Some risk factors for non-adherence are well known but the full range of risk factors remains unclear. Non-adherence to immunosuppressants and to other components of the regimen increases morbidity and mortality risks. Recent interventions, including education and counseling; electronic health strategies; and medication dose modifications, show promise for reducing immunosuppressant non-adherence. However, most of these interventions would be difficult to deploy in everyday clinical practice. Systematic dissemination of efficacious interventions into clinical practice has not been undertaken. SUMMARY: Rates and risk factors for non-adherence to the medical regimen have been examined and there is evidence that non-adherence may be ameliorated by a range of interventions. Although gaps in the evidence base remain, it would be timely to devote greater efforts to dissemination of findings. Thus, efforts are needed to assist transplant programs in using existing evidence to better identify patients who are non-adherent and to design and implement strategies to reduce or prevent non-adherence.

Psychiatric Predictors of Long-term Transplant-Related Outcomes in Lung Transplant Recipients.

BACKGROUND: Long-term survival after lung transplantation remains poor, yet modifiable risk factors for late-term morbidity and mortality have yet to be identified. Because psychiatric disorders increase risk for poor health outcomes in many nontransplant chronic disease populations, lung recipients with depression or anxiety before or early after transplantation may be at heightened risk for late-term transplant-related morbidity and mortality. METHODS: Among 178 patients from a prospective study of mental health after lung transplantation, we identified 1-year survivors and examined whether they experienced major depression or anxiety disorders during that year as well as before transplantation. We used multivariable Cox regression to examine the relationship between these disorders and risk for subsequent bronchiolitis obliterans syndrome (BOS), mortality and graft loss for up to 15 years posttransplant, controlling for other known risk factors for the outcomes. RESULTS: One hundred fifty-five recipients were studied. Recipients with posttransplant depression had an elevated risk of BOS (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 1.10-3.31), patient death (HR, 1.65; 95% CI, 1.01-2.71) and graft loss (HR, 1.75; 95% CI, 1.06-2.88). A trend toward reduced risk of BOS was observed in recipients with posttransplant anxiety (HR, 0.61; 95%CI, 0.37-1.00). Neither pretransplant disorder was related to risk for any outcome. CONCLUSIONS: Early posttransplant depression increases risk for long-term transplant-related morbidity and mortality. Screening to identify depression should therefore be routine in posttransplant care. Although anxiety was not significantly associated with poor outcomes, screening for posttransplant anxiety should also be routine, to reduce patient distress. Research is needed to better understand mechanisms underlying depression-outcome associations.

Depression and Anxiety as Risk Factors for Morbidity and Mortality After Organ Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Depression and anxiety are common mental health problems in transplant populations. There is mixed evidence concerning whether they increase morbidity and mortality risks after transplantation. If such associations exist, additional risk reduction strategies may be needed. METHODS: Four bibliographic databases were searched from 1981 through September 2014 for studies prospectively examining whether depression or anxiety (determined with diagnostic evaluations or standardized symptom scales) affected risk for posttransplant mortality, graft loss, acute graft rejection, chronic rejection, cancer, infection, and rehospitalization. RESULTS: Twenty-seven studies (10 heart, total n = 1738; 6 liver, n = 1063; 5 kidney, n = 49515; 4 lung, n = 584; 1 pancreas, n = 80; 1 mixed recipient sample, n = 205) were identified. In each, depression and/or anxiety were typically measured before or early after transplantation. Follow-up for outcomes was a median of 5.8 years (range, 0.50-18.0). Depression increased the relative risk (RR) of mortality by 65% (RR, 1.65; 95% confidence interval [95% CI], 1.34-2.05; 20 studies). Meta-regression indicated that risk was stronger in studies that did (vs did not) control for potential confounders (P = .032). Risk was unaffected by type of transplant or other study characteristics. Depression increased death-censored graft loss risk (RR, 1.65; 95% CI, 1.21-2.26, 3 studies). Depression was not associated with other morbidities (each morbidity was assessed in 1-4 studies). Anxiety did not significantly increase mortality risk (RR, 1.39; 95% CI, 0.85-2.27, 6 studies) or morbidity risks (assessed in single studies). CONCLUSIONS: Depression increases risk for posttransplant mortality. Few studies considered morbidities; the depression-graft loss association suggests that linkages with morbidities deserve greater attention. Depression screening and treatment may be warranted, although whether these activities would reduce posttransplant mortality requires study.

Predictors of post-traumatic psychological growth in the late years after lung transplantation.

BACKGROUND: Although lung transplantation improves quality of life, most psychosocial research focuses on adverse psychological and social functioning outcomes. Positive effects, particularly in the late-term years as physical morbidities increase, have received little attention. We provide the first data on a psychological benefit - post-traumatic growth (PTG) - and we focused on long-term (>5 yr) survivors. METHODS: Among 178 patients from a prospective study of mental health during the first two yr post-transplant, we recontacted survivors 6-11 yr post-transplant. We assessed PTG (i.e., positive psychological change resulting from the transplant) and examined its relationship to other patient characteristics with multivariable regression analyses. RESULTS: Sixty-four patients (86% of survivors) were assessed (M = 8.1 yr post-transplant, SD = 1.2). Mean PTG exceeded the scale's midpoint (M = 38.6, SD = 10.0; scale midpoint = 25). Recipients experiencing greater PTG were female (p = 0.022), less educated (p = 0.014), and had a history of post-transplant panic disorder (p = 0.005), greater friend support (p = 0.048), and better perceived health (p = 0.032). Neither other pre- or post-transplant mood and anxiety disorders nor transplant-related morbidities (acute rejection, bronchiolitis obliterans syndrome) predicted PTG. CONCLUSIONS: PTG exceeded levels observed in other chronic disease populations, suggesting that lung transplantation may uniquely foster positive psychological change in long-term survivors. PTG occurs despite physical and psychiatric morbidities. Whether PTG promotes other positive post-transplant psychosocial outcomes deserves attention.

Psychosocial issues facing lung transplant candidates, recipients and family caregivers.

Although lung transplantation is an accepted treatment for many individuals with severe lung disease, transplant candidates and recipients experience a range of psychosocial stressors that begin at the initiation of the transplant evaluation and continue throughout patients' wait for donor lungs, their perioperative recovery, and their long-term adjustment to posttransplant life. Transplant programs should strive to incorporate evidence-based interventions that aim to improve physical functioning, psychological distress, global quality of life, and medical adherence as well as to integrate symptom management and palliative care strategies throughout the pre- and posttransplantation course.

Prevention of poor psychosocial outcomes in living organ donors: from description to theory-driven intervention development and initial feasibility testing.

CONTEXT: Although some living donors experience psychological, somatic, and interpersonal difficulties after donation, interventions to prevent such outcomes have not been developed or evaluated. OBJECTIVE: To (1) summarize empirical evidence on psychosocial outcomes after donation, (2) describe a theoretical framework to guide development of an intervention to prevent poor outcomes, and (3) describe development and initial evaluation of feasibility and acceptability of the intervention. METHODS: Based on a narrative literature review suggesting that individuals ambivalent about donation are at risk for poor psychosocial outcomes after donation, the intervention targeted this risk factor. Intervention structure and content drew on motivational interviewing principles in order to assist prospective donors to resolve ambivalence. Data were collected on donors' characteristics at our institution to determine whether they constituted a representative population in which to evaluate the intervention. Study participants were then recruited to assess the feasibility and acceptability of the intervention. They were required to have scores greater than 0 on the Simmons Ambivalence Scale (indicating at least some ambivalence about donation). RESULTS: Our population was similar to the national living donor population on most demographic and donation-related characteristics. Eight individuals who had been approved to donate either a kidney or liver segment were enrolled for pilot testing of the intervention. All successfully completed the 2-session telephone-based intervention before scheduled donation surgery. Participants' ratings of acceptability and satisfaction were high. Open-ended comments indicated that the intervention addressed participants' thoughts and concerns about the decision to donate. CONCLUSIONS: The intervention is feasible, acceptable, and appears relevant to donor concerns. A clinical trial to evaluate the efficacy of the intervention is warranted.

Onset and risk factors for anxiety and depression during the first 2 years after lung transplantation.

OBJECTIVE: Anxiety disorders are prominent in chronic lung disease; lung transplant recipients may therefore also be at high risk for these disorders. We sought to provide the first prospective data on rates and risk factors for anxiety disorders as well as depressive disorders during the first 2 years after transplantation. METHOD: A total of 178 lung recipients and a comparison group (126 heart recipients) received psychosocial and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition assessments at 2, 7, 12, 18 and 24 months posttransplant. Survival analysis determined onset rates and risk factors. RESULTS: The panic disorder rate was higher (P<.05) in lung than heart recipients (18% vs. 8%). Lung and heart recipients did not differ on rates of transplant-related posttraumatic stress disorder (15% vs. 14%), generalized anxiety disorder (4% vs. 3%) or major depression (30% vs. 26%). Risk factors for disorders included pretransplant psychiatric history, female gender, longer wait for transplant, and early posttransplant health problems and psychosocial characteristics (e.g., poorer caregiver support and use of avoidant coping). CONCLUSIONS: Heightened vigilance for panic disorder in lung recipients and major depression in all cardiothoracic recipients is warranted. Strategies to prevent psychiatric disorder should target recipients based not only on pretransplant characteristics but on early posttransplant characteristics as well.

Five-year outcomes with alemtuzumab induction after lung transplantation.

BACKGROUND: Induction therapy with alemtuzumab, followed by lower than conventional intensity post-transplant immunosuppression (eg, tacrolimus monotherapy), has been associated with reduced morbidity and mortality in abdominal and heart transplantation. We examined 5-year outcomes in lung recipients receiving alemtuzumab in conjunction with reduced-intensity post-transplant immunosuppression (early lower-dose tacrolimus; lower-dose steroids, with or without mycophenolate mofetil), compared with lung recipients receiving other induction agents or no induction in association with post-transplant immunosuppression. METHODS: A retrospective analysis was performed using prospectively collected data from a single-site clinical database of 336 lung recipients (aged ≥ 18) who received allografts between 1998 and 2005, classified by induction type: alemtuzumab, 127; Thymoglobulin, 43; daclizumab, 73; and none, 93. Survival analyses examined patient and graft survival, and freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, obliterative bronchiolitis (OB), bronchiolitis obliterans syndrome (BOS), and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Five-year patient and graft survival differed by group (p = 0.046, p = 0.038, respectively). Alemtuzumab patient/graft survival rates were 59%/59%. Survival rates were 60%/44% for Thymoglobulin, 47%/46% for no induction, and 44%/41% for daclizumab. Freedom from ACR, lymphocytic bronchiolitis, OB, and BOS differed by group (all values, p < 0.008); alemtuzumab recipients showed greater 5-year freedom from each outcome (30%/82%/86%/54%) than Thymoglobulin (20%/54%/62%/27%), daclizumab (19%/55%/70%/43%), and no-induction groups (18%/70%/69%/46%). The groups did not differ in PTLD rates (≥ 94% free of PTLD at 5 years; p = 0.864). Effects were unchanged after controlling for potential covariates. CONCLUSIONS: Alemtuzumab induction may be associated with improved outcomes in lung transplantation. Randomized controlled trials are needed to establish any effects of this agent.

Exploring the meaning of chronic rejection after lung transplantation and its impact on clinical management and caregiving.

Although the literature continues to portray chronic rejection after lung transplantation as ominous with no known treatment, no studies have examined family and clinician caregivers' perceptions of the diagnosis of chronic rejection and its impact on the course of clinical care. We explored the meaning and impact of chronic rejection from the perspective of family (n=10) and clinician (n=3) caregivers. We found that family caregivers considered the onset of chronic rejection to be inevitable, irreversible, unpredictable, and going back to pretransplant. Clinicians considered chronic rejection as a harbinger of deterioration and peril and expressed trepidation about informing recipients and their family caregivers about the diagnosis. Despite the heightened caregiving duties and challenges of treating chronic rejection, its unpredictable course and the prospect of retransplant instilled hope for stabilization or cure among most clinicians and caregivers, leading them to support recipients' wishes to pursue potentially futile treatments. Until recipients were no longer competent, caregivers believed all treatment options (including retransplant) had been exhausted, or suffering was prolonged, caregivers were reluctant to halt extraordinary treatment measures. Caregivers perceived that certainty regarding poor prognosis was required for palliative care and that palliative care was end-of-life care. Consequently, trials of aggressive treatment typically precluded palliative care.