Larissa Myaskovsky

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.

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.

Muscle mass predicts outcomes following liver transplantation

For patients with end‐stage liver disease, commonly used indices of nutritional status (ie, body weight and body mass index) are often inflated because of fluid overload (ie, ascites and peripheral edema), and this results in an underdiagnosis of malnutrition. Because muscle is the largest protein reservoir in the body, an estimate of the muscle mass may be a more reliable and valid estimate of nutritional status. Therefore, we used pretransplant computed tomography data for 338 liver transplantation (LT) candidates to identify muscle and fat mass on the basis of a specific abdominal transverse section commonly used in body composition analyses, and we investigated the contribution of this measure to specific post‐LT outcomes. We found that the majority of our patients (68%) could be defined as cachectic. For men, muscle mass predicted many important posttransplant outcomes, including intensive care unit (ICU) stay, total length of stay (LOS), and days of intubation. Muscle mass was a significant predictor of survival and also predicted disposition to home versus another facility. For women, muscle mass predicted ICU stay, total LOS, and days of intubation, but the effect was modest. Muscle mass did not predict survival or disposition for women. In conclusion, because pretransplant muscle mass is associated with many important postoperative outcomes, we discuss these findings in the context of possible pretransplant interventions for either improving or sustaining muscle mass before surgery. Liver Transpl 19:1172‐1180, 2013.

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.

Race and ethnicity in decisions about unrelated hematopoietic stem cell donation

Large international registries of potential unrelated hematopoietic stem cell (HSC) donors, including the National Marrow Donor program (NMDP), continue to face difficulties finding matched donors for racial/ethnic minorities. One reason, in addition to the generally less common HLA types among minority patients, is the much higher registry attrition rate of racial/ethnic minorities compared with whites. Reasons for the higher attrition among minority potential donors remain unexplained. The goal of our cross-sectional telephone interview study was to generate a diverse sample of potential HSC donors who have preliminarily matched a patient and to identify factors associated with race/ethnicity and with the decision to continue toward potential donation or to opt out of the registry. Multiple culturally related, psychosocial, and donation-related factors were associated both with race/ethnic group membership and attrition from the registry. The most consistent factor associated with opting out of the registry across all race/ethnic groups was ambivalence about donation: doubts and worries, feeling unsure about donation, wishing someone else would donate in ones place. Our findings suggest that universal donor recruitment and management approaches based on reducing donation-related ambivalence and tailored messages and strategies for each of the individual race/ethnic groups are important.

Objective radiologic assessment of body composition in patients with end-stage liver disease: going beyond the BMI.

Background Body mass index (BMI) is a commonly used but likely inexact measure of body composition for patients with end-stage liver disease. For this reason, we examined whether body composition measurements from direct visualization on computed tomography (CT) scans provide new insights in both the degree of malnutrition and the discordant combinations such as obesity with muscle mass loss. This technology is widely used in other medically ill populations but not yet in liver transplantation. Methods We examined actual body composition using abdominal CT scan data and software designed to measure fat and muscle compartments. Results In 234 liver transplant candidates, we found that BMI was highly and significantly correlated to subcutaneous and visceral fat. However, we additionally found that, even among obese patients, cachexia, as defined by muscle mass, was common, with 56% of those with BMI above 30 being cachexic. We also found that patients with nonalcoholic steatohepatitis, compared with other types of liver diseases, were significantly more likely to have larger amounts of visceral fat while also having less muscle. In an exploratory analysis, muscle mass corrected for height was a significant predictor of posttransplantation survival. Conclusions Body composition by CT scan data provides a specific method to identify obesity and muscle wasting for end-stage liver disease patients. Whether these data can aid in the prognostication of outcomes and survival requires further investigation.

Factors associated with ambivalence about bone marrow donation among newly recruited unrelated potential donors.

Background. Previous research has indicated that feelings of ambivalence about donation are associated with donors’ decisions not to donate and with less positive physical and psychosocial outcomes among donors who donated despite feeling ambivalent. The current study examines the prevalence of ambivalence among newly recruited potential bone marrow donors and identifies factors associated with greater ambivalence. Methods. Using a cross-sectional design, questionnaires were mailed to a stratified random sample of individuals newly recruited to the National Marrow Donor Program registry at 71 local donor centers. A total of 426 new recruits (63%) completed and returned the questionnaire. Results. Bivariate analyses indicated that multiple recruitment experience and donor perception variables were significantly associated with ambivalence. Multivariate analysis revealed that the following eight variables were uniquely associated with higher levels of ambivalence after adjusting for the effects of other key indicators: participating in other volunteer activities, joining at a drive for a specific patient, perceiving the recruitment staff as less informative, being discouraged from joining by others, not having an intrinsic commitment to donate, being encouraged by one’s culture or religion to join, believing there are risks to donation, and having a greater number of medical, work, and family concerns about donation. Conclusions. Potential donors who are motivated by an intrinsic commitment to donate, rather than extrinsic pressure, are less ambivalent about donating. In addition, recruitment staff have a potentially critical role in reducing ambivalence among new recruits by providing information that may allay any unrealistic concerns recruits may have about the medical risks and impact of donation on work and family.