Galen E. Switzer

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.

Advancing Health Disparities Research Within the Health Care System: A Conceptual Framework

We provide a framework for health services-related researchers, practitioners, and policy makers to guide future health disparities research in areas ranging from detecting differences in health and health care to understanding the determinants that underlie disparities to ultimately designing interventions that reduce and eliminate these disparities. To do this, we identified potential selection biases and definitions of vulnerable groups when detecting disparities. The key factors to understanding disparities were multilevel determinants of health disparities, including individual beliefs and preferences, effective patient-provider communication; and the organizational culture of the health care system. We encourage interventions that yield generalizable data on their effectiveness and that promote further engagement of communities, providers, and policymakers to ultimately enhance the application and the impact of health disparities research.

Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance: Another Paradox in Endurance-Trained Athletes?

OBJECTIVE Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.

Posttraumatic stress disorder and service utilization among urban mental health center clients.

Although the urban poor are at high risk for exposure to trauma, community mental health clinics rarefy diagnose clients with PTSD. Failure to diagnose PTSD may undermine the effectiveness of services provided. Our objectives were to (1) assess prevalence of traumatic experiences and PTSD, and (2) examine differences in service utilization between those who had PTSD and those who did not. Interview data were gathered from 181 urban psychiatric outpatients. A substantial number of clients had experienced at least one lifetime trauma (94%), and of those, 42% had PTSD during the past year. Analyses comparing service use between PTSD and nonPTSD clients supported our expectation that clients with PTSD would use more mental health services, and would be less satisfied with services than their nonPTSD counterparts.

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.

PTSD in Heart Transplant Recipients and Their Primary Family Caregivers

Posttraumatic stress disorder associated with transplantation (PTSD-T) is a complication for some heart transplant recipients. By using a structured, standardized interview and DSM-III-R criteria, the authors examined whether recipients (n = 158) and their family caregivers (n = 142) showed similar PTSD-T rates and clinical characteristics during the first year posttransplant. Among the recipients, 10.5% met full criteria for the disorder and an additional 5% were probable cases. Among the caregivers, 7.7% met full criteria and an additional 11.0% were probable cases. Severity and duration of disorder were similar across the groups. Being female, having a history of psychiatric illness, and having lower friend support were increased risks for PTSD-T.

Assessment of optimal size and composition of the U.S. National Registry of hematopoietic stem cell donors.

Background. The National Marrow Donor Program (NMDP) receives federal funding to operate a registry of over 4 million volunteer donors for patients in need of a hematopoietic stem cell transplant. Because minority patients are less likely to find a suitably matched donor than whites, special efforts have been aimed toward recruitment of minorities. Significant financial resources are required to recruit and tissue type additional volunteer donors. Methods. Population genetics models have been constructed to project likelihoods of finding a human leukocyte antigen (HLA)-matched donor for patients of various racial/ethnic groups. These projections have been made under a variety of strategies for expansion of the NMDP Registry. Cost-effectiveness calculations incorporated donor unavailability and other barriers to transplantation. Results. At current recruitment rates, the probability of an available HLA-A,B,DRB1 matched donor is projected to increase from 27% to 34%; 45% to 54%; 75% to 79%; and 48% to 55%, for blacks, Asians/Pacific Islanders, whites and Hispanics, respectively, by the year 2007. Substantial increases in minority recruitment would have only modest impacts on these projections. These projections are heavily affected by donor availability rates, which are less than 50% for minority volunteers. Conclusions. Continued recruitment of additional volunteers can improve the likelihood of finding an HLA-matched donor, but will still leave significant numbers of patients of all racial/ethnic groups without a match. Efforts to improve donor availability (especially among minorities) and to increase the number of patients with access to the NMDP Registry may prove to be more cost-effective means of increasing transplants.

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.

Race and socioeconomic status influence outcomes of unrelated donor hematopoietic cell transplantation.

Success of hematopoietic cell transplantation (HCT) can vary by race, but the impact of socioeconomic status (SES) is not known. To evaluate the role of race and SES, we studied 6207 unrelated-donor myeloablative (MA) HCT recipients transplanted between 1995 and 2004 for acute or chronic leukemia or myelodysplastic syndrome (MDS). Patients were reported by transplant center to be White (n = 5253), African American (n = 368), Asian/Pacific-Islander (n = 141), or Hispanic (n = 445). Patient income was estimated from residential zip code at time of HCT. Cox regression analysis adjusting for other significant factors showed that African American (but not Asian or Hispanic) recipients had worse overall survival (OS) (relative-risk [RR] 1.47; 95% confidence interval [CI] 1.29-1.68, P < .001) compared to Whites. Treatment-related mortality (TRM) was higher in African Americans (RR 1.56; 95% CI 1.34-1.83, P < .001) and in Hispanics (RR 1.30; 95% CI 1.11-1.51, P = .001). Across all racial groups, patients with median incomes in the lowest quartile (<

Patient Satisfaction in Resident and Attending Ambulatory Care Clinics

34,700) had worse OS (RR 1.15; 95% CI 1.04-1.26, P = .005) and higher risks of TRM (RR 1.21; 1.07-1.36, P = .002). Inferior outcomes among African Americans are not fully explained by transplant-related factors or SES. Potential other mechanisms such as genetic polymorphisms that have an impact on drug metabolism or unmeasured comorbidities, socioeconomic factors, and health behaviors may be important. Low SES, regardless of race, has a negative impact on unrelated donor HCT outcomes.