Andrea F. DiMartini

Rates and risk factors for nonadherence to the medical regimen after adult solid organ transplantation.

Background. Despite the impact of medical regimen nonadherence on health outcomes after organ transplantation, there is mixed and conflicting evidence regarding the prevalence and predictors of posttransplant nonadherence. Clinicians require precise information on nonadherence rates in order to evaluate patients’ risks for this problem. Methods. A total of 147 studies of kidney, heart, liver, pancreas/kidney-pancreas, or lung/heart-lung recipients published between 1981 and 2005 were included in a meta-analysis. Average nonadherence rates were calculated for 10 areas of the medical regimen. Correlations between nonadherence and patient psychosocial risk factors were examined. Results. Across all types of transplantation, average nonadherence rates ranged from 1 to 4 cases per 100 patients per year (PPY) for substance use (tobacco, alcohol, illicit drugs), to 19 to 25 cases per 100 PPY for nonadherence to immunosuppressants, diet, exercise, and other healthcare requirements. Rates varied significantly by transplant type in two areas: immunosuppressant nonadherence was highest in kidney recipients (36 cases per 100 PPY vs. 7 to 15 cases in other recipients). Failure to exercise was highest in heart recipients (34 cases per 100 PPY vs. 9 to 22 cases in other recipients). Demographics, social support, and perceived health showed little correlation with nonadherence. Pretransplant substance use predicted posttransplant use. Conclusions. The estimated nonadherence rates, overall and by transplant type, allow clinicians to gauge patient risk and target resources accordingly. Nonadherence rates in some areas—including immunosuppressant use—appear unacceptably high. Weak correlations of most patient psychosocial factors with nonadherence suggest that attention should focus on other classes of variables (e.g., provider-related and systems-level factors), which may be more influential.

Meta-Analysis of Risk for Relapse to Substance Use After Transplantation of the Liver or Other Solid Organs

For patients receiving liver or other organ transplants for diseases associated with substance use, risk for relapse posttransplantation is a prominent clinical concern. However, there is little consensus regarding either the prevalence or risk factors for relapse to alcohol or illicit drug use in these patients. Moreover, the evidence is inconsistent as to whether patients with pretransplantation substance use histories show poorer posttransplantation medical adherence. We conducted a meta‐analysis of studies published between 1983 and 2005 to estimate relapse rates, rates of nonadherence to the medical regimen, and the association of potential risk factors with these rates. The analysis included 54 studies (50 liver, 3 kidney, and 1 heart). Average alcohol relapse rates (examined only in liver studies) were 5.6 cases per 100 patients per year (PPY) for relapse to any alcohol use and 2.5 cases per 100 PPY for relapse with heavy alcohol use. Illicit drug relapse averaged 3.7 cases per 100 PPY, with a significantly lower rate in liver vs. other recipients (1.9 vs. 6.1 cases). Average rates in other areas (tobacco use, immunosuppressant and clinic appointment nonadherence) were 2 to 10 cases per 100 PPY. Risk factors could be examined only for relapse to any alcohol use. Demographics and most pretransplantation characteristics showed little correlation with relapse. Poorer social support, family alcohol history, and pretransplantation abstinence of ≤6 months showed small but significant associations with relapse (r = 0.17‐0.21). Future research should focus on improving the prediction of risk for substance use relapse, and on testing interventions to promote continued abstinence posttransplantation. Liver Transpl 14:159–172. 2008.

Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression.

Objective: To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure. Background: Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol (“Pittsburgh protocol”). Methods: Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring. Results: All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates. Conclusions: Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.

Meta-Analysis of Medical Regimen Adherence Outcomes in Pediatric Solid Organ Transplantation*

Background. Adherence to the medical regimen after pediatric organ transplantation is important for maximizing good clinical outcomes. However, the literature provides inconsistent evidence regarding prevalence and risk factors for nonadherence posttransplant. Methods. A total of 61 studies (30 kidney, 18 liver, 8 heart, 2 lung/heart-lung, and 3 with mixed recipient samples) were included in a meta-analysis. Average rates of nonadherence to six areas of the regimen, and correlations of potential risk factors with nonadherence, were calculated. Results. Across all types of transplantation, nonadherence to clinic appointments and tests was most prevalent, at 12.9 cases per 100 patients per year (PPY). The immunosuppression nonadherence rate was six cases per 100 PPY. Nonadherence to substance use restrictions, diet, exercise, and other healthcare requirements ranged from 0.6 to 8 cases per 100 PPY. Only the rate of nonadherence to clinic appointments and tests varied by transplant type: heart recipients had the lowest rate (4.6 cases per 100 PPY vs. 12.7–18.8 cases per 100 PPY in other recipients). Older age of the child, family functioning (greater parental distress and lower family cohesion), and the child’s psychological status (poorer behavioral functioning and greater distress) were among the psychosocial characteristics significantly correlated with poorer adherence. These correlations were small to modest in size (r=0.12–0.18). Conclusions. These nonadherence rates provide benchmarks for clinicians to use to estimate patient risk. The identified psychosocial correlates of nonadherence are potential targets for intervention. Future studies should focus on improving the prediction of nonadherence risk and on testing interventions to reduce risk.

Adherence to the medical regimen during the first two years after lung transplantation.

Background. Despite the importance of adherence to the medical regimen for maximizing health after lung transplantation, no prospective studies report on rates or risk factors for nonadherence in this patient population. Whether adherence levels differ in lung versus other types of transplant recipients is unknown. Methods. A total of 178 lung recipients and a comparison group of 126 heart recipients were enrolled. Adherence in nine areas was assessed in separate patient and family caregiver interviews 2, 7, 12, 18, and 24 months posttransplant. Potential risk factors for nonadherence were obtained at the initial assessment. Results. Cumulative incidence rates of persistent nonadherence (i.e., nonadherence at ≥2 consecutive assessments) were significantly lower (P<0.05) in lung recipients than heart recipients for taking immunosuppressants (13% nonadherent vs. 21%, respectively), diet (34% vs. 56%), and smoking (1% vs. 8%). Lung recipients had significantly higher persistent nonadherence to completing blood work (28% vs. 17%) and monitoring blood pressure (70% vs. 59%). They had a high rate of spirometry nonadherence (62%; not measured in heart recipients). The groups did not differ in nonadherence to attending clinic appointments (27%), exercise (44%), or alcohol limitations (7%). In both groups, poor caregiver support and having only public insurance (e.g., Medicaid) increased nonadherence risk in all areas. Conclusions. Lung recipients were neither uniformly better nor worse than heart recipients in adhering to their regimen. Lung recipients have particular difficulty with some home monitoring activities. Strategies to maximize adherence in both groups should build on caregiver support and on strengthening financial resources for patient healthcare requirements.

Psychological disorders and distress after adult cardiothoracic transplantation.

This review summarizes and integrates evidence concerning mental health outcomes following heart, lung, and heart-lung transplantation. Drawing on English-language case reports and empirical studies published between January 1980 and December 2004, the goals of the review were to (a) describe the prevalence and clinical characteristics of psychological disorders, as well as the level and pattern of clinically significant distress in the years posttransplant; (b) review the major risk factors for poor posttransplant psychological outcomes; (c) consider evidence suggesting that posttransplant psychological outcomes predict physical morbidity and mortality after transplant; (d) summarize findings from intervention studies designed to improve posttransplant psychological outcomes; and (e) provide patient care recommendations for the practicing clinician and recommendations for continued clinical research. Several major conclusions can be drawn from this literature. First, depressive and anxiety-related disorders and associated distress are common posttransplant. While new onsets of disorder may decline after the first year posttransplant, the development of new medical complications in the late years posttransplant may provoke renewed distress and recurrences of disorder. Second, risk factors for posttransplant psychological disorders and elevated distress include both standard risk factors observed in other populations (eg, younger age, lifetime history of psychiatric disorder) and transplant-specific factors related to physical functional impairments, social supports, and strategies for coping with health problems. Third, while little evidence has been published to date, there is some indication that posttransplant psychological outcomes can predict subsequent physical health outcomes. Fourth, extremely few intervention studies in cardiothoracic transplant recipients have been performed. The few reports indicate that multicomponent psychosocial strategies focused on risk factor reduction and enhancement of personal coping resources may lead to reductions in psychological distress. An important caveat in considering all of the evidence reviewed is that most studies focus on heart rather than lung or heart-lung recipients. Recommendations for practicing clinicians focus on assessment and treatment options, based on the evidence to date. Research recommendations focus on the need for intervention effectiveness studies.

Early Trajectories of Depressive Symptoms after Liver Transplantation for Alcoholic Liver Disease Predicts Long‐Term Survival

Although it is well known that depression is associated with poorer medical outcomes, the association between depression‐ and liver transplant (LTX)‐specific outcomes has not been investigated. We identified three trajectories of depressive symptoms evolving within the first post‐LTX year in a cohort of 167 patients transplanted for alcoholic cirrhosis: a group with consistently low depression levels at all time points (group 1, n = 95), a group with initially low depression levels that rose over time (group 2, n = 41), and a group with consistently high depression levels (group 3, n = 31). Controlling for medical factors associated with poorer survival, recipients with increasing depression or persisting depression were more than twice as likely to die (all cause mortality) within the subsequent years. At 10 years post‐LTX the survival rate was 66% for the low depression group, but only 46% and 43%, respectively, for the increasing depression and high depression groups. Except for a paradoxically higher percentage of malignancies in the low depression group, the causes of death and other specific LTX outcomes were not different between groups. Whether treatment of depression will improve survival rates is an area for research.

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.

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.

Preventive Intervention for Living Donor Psychosocial Outcomes: Feasibility and Efficacy in a Randomized Controlled Trial

There are no evidence‐based interventions to prevent adverse psychosocial consequences after living donation. We conducted a single‐site randomized controlled trial to examine the postdonation impact of a preventive intervention utilizing motivational interviewing (MI) to target a major risk factor for poor psychosocial outcomes, residual ambivalence (i.e. lingering hesitation and uncertainty) about donating. Of 184 prospective kidney or liver donors, 131 screened positive for ambivalence; 113 were randomized to (a) the MI intervention, (b) an active comparison condition (health education) or (c) standard care only before donation. Ambivalence was reassessed postintervention (before donation). Primary trial outcomes—psychosocial variables in somatic, psychological and family interpersonal relationship domains—were assessed at 6 weeks and 3 months postdonation. MI subjects showed the greatest decline in ambivalence (p = 0.050). On somatic outcomes, by 3 months postdonation MI subjects reported fewer physical symptoms (p = 0.038), lower rates of fatigue (p = 0.021) and pain (p = 0.016), shorter recovery times (p = 0.041) and fewer unexpected medical problems (p = 0.023). Among psychological and interpersonal outcomes, they had a lower rate of anxiety symptoms (p = 0.046) and fewer unexpected family‐related problems (p = 0.045). They did not differ on depression, feelings about donation or family relationship quality. The findings suggest that the intervention merits testing in a larger, multisite trial.