Margaret Stedman

All Publications

• Empowering collaborative statisticians: The impact of the American Statistical Association's Pathways to Promotion Committee STAT Stedman, M. R., Dehom, S., Davidson, M. A., Zhang, L., Podolsky, R. H., Pohlig, R. T., Coffey, T. 2024; 13 (3)

  View details for DOI 10.1002/sta4.716

  View details for Web of Science ID 001283391800001

• Physical function and mortality in older adults with chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN Liu, C. K., Parvathinathan, G., Stedman, M. R., Seliger, S. L., Weiner, D. E., Tamura, M. K. 2024

  Abstract

  Accurate mortality prediction can guide clinical care for older adults with chronic kidney disease (CKD). Yet existing tools do not incorporate physical function, an independent predictor of death in older adults. We determined whether incorporating physical function measurements improve mortality prediction among older adults with CKD.We included Chronic Renal Insufficiency Cohort participants who were ≥65 years old, had estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2, not receiving kidney failure replacement therapy (KFRT), and had least one gait speed assessment. Gait speed was measured at usual pace (≥0.84, 0.83-0.65, 0.64-0.47, ≤0.46 meters/second, or unable), and frailty was assessed using Physical Frailty Phenotype criteria (range 0 to 5 points, also known as Fried criteria). We modeled time to all-cause death over five years using Cox proportional hazard models, treating KFRT as censored and non-censored events in separate analyses. C-statistics assessed model discrimination.Among 2,338 persons, mean age was 70±4 years; 43% were female and 43% were Black. Mean eGFR was 42±13 mL/min/1.73m2 and median urine albumin-to-creatinine ratio was 33 mg/g [Q1 9, Q3 206]. Over a median follow-period of 5 years, 392 died and 164 developed KFRT. In censored analyses, adding gait speed or frailty improved mortality risk prediction. The C-statistic changed from 0.69 to 0.72 with gait speed scores, and from 0.70 to 0.73 with frailty scores. The performance of models with gait speed or frailty was similar in non-censored analyses.Among older adults with CKD, adding measures of physical function modestly improves mortality prediction.

  View details for DOI 10.2215/CJN.0000000000000515

  View details for PubMedID 39115956

• Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities. Transplantation direct Caldwell, J. S., Parvathinathan, G., Stedman, M. R., Ahearn, P., Tan, J. C., Cheng, X. S. 2024; 10 (7): e1653

  Abstract

  Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities.We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death.We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10).Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

  View details for DOI 10.1097/TXD.0000000000001653

  View details for PubMedID 38881747

  View details for PubMedCentralID PMC11177818

• Endovascular versus Surgical Lower Extremity Revascularization among Patients with Chronic Kidney Disease. International journal of nephrology Chen, Q., Han, J., Parvathinathan, G., Ross, E., Stedman, M. R., Chang, T. I. 2023; 2023: 5586060

  Abstract

  Patients with chronic kidney disease (CKD) have a high prevalence of peripheral artery disease. How best to manage lower extremity peripheral artery disease remains unclear in this patient population. We therefore sought to compare the outcomes after endovascular versus surgical lower extremity revascularization among patients with CKD.We used data from Optum's de-identifed Clinformatics® Data Mart Database, a nationwide database of commercially insured persons in the United States to study patients with CKD who underwent lower extremity endovascular or surgical revascularization. We used inverse probability of treatment weighting to balance covariates. We employed proportional hazard regression to study the primary outcome of major adverse limb events (MALE), defined as a repeat revascularization or amputation. We also studied each of these events separately and death from any cause.In our cohort, 60,057 patients underwent endovascular revascularization and 9,338 patients underwent surgical revascularization. Endovascular revascularization compared with surgical revascularization was associated with a higher adjusted hazard of MALE (hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.46-1.59). Endovascular revascularization was also associated with a higher adjusted hazard of repeat revascularization (HR 1.65; 95% CI 1.57-1.72) but a lower adjusted risk of amputation (HR 0.71; CI 0.73-0.89). Patients undergoing endovascular revascularization also had a lower adjusted hazard for death from any cause (0.85; CI 0.82-0.88).In this analysis of patients with CKD undergoing lower extremity revascularization, an endovascular approach was associated with a higher rate of repeated revascularization but a lower risk of subsequent amputation and death compared with surgical revascularization. Multiple factors must be considered when counseling patients with CKD, who have a high burden of comorbid conditions. Clinical trials should include more patients with kidney disease, who are often otherwise excluded from participation, to better understand the most effective treatment strategies for this vulnerable patient population.

  View details for DOI 10.1155/2023/5586060

  View details for PubMedID 38144229

  View details for PubMedCentralID PMC10748729

• "Diving in the deep-end and swimming": a mixed methods study using normalization process theory to evaluate a learning collaborative approach for the implementation of palliative care practices in hemodialysis centers. BMC health services research Holdsworth, L. M., Stedman, M., Gustafsson, E. S., Han, J., Asch, S. M., Harbert, G., Lorenz, K. A., Lupu, D. E., Malcolm, E., Moss, A. H., Nicklas, A., Tamura, M. K. 2023; 23 (1): 1384

  Abstract

  Normalization Process Theory (NPT) is an implementation theory that can be used to explain how and why implementation strategies work or not in particular circumstances. We used it to understand the mechanisms that lead to the adoption and routinization of palliative care within hemodialysis centers.We employed a longitudinal, mixed methods approach to comprehensively evaluate the implementation of palliative care practices among ten hemodialysis centers participating in an Institute for Healthcare Improvement Breakthrough- Series learning collaborative. Qualitative methods included longitudinal observations of collaborative activities, and interviews with implementers at the end of the study. We used an inductive and deductive approach to thematic analysis informed by NPT constructs (coherence, cognitive participation, collective action, reflexive monitoring) and implementation outcomes. The NoMAD survey, which measures NPT constructs, was completed by implementers at each hemodialysis center during early and late implementation.The four mechanisms posited in NPT had a dynamic and layered relationship during the implementation process. Collaborative participants participated because they believed in the value and legitimacy of palliative care for patients receiving hemodialysis and thus had high levels of cognitive participation at the start. Didactic Learning Sessions were important for building practice coherence, and sense-making was solidified through testing new skills in practice and first-hand observation during coaching visits by an expert. Collective action was hampered by limited time among team members and practical issues such as arranging meetings with patients. Reflexive monitoring of the positive benefit to patient and family experiences was key in shifting mindsets from disease-centric towards a patient-centered model of care. NoMAD survey scores showed modest improvement over time, with collective action having the lowest scores.NPT was a useful framework for understanding the implementation of palliative care practices within hemodialysis centers. We found a nonlinear relationship among the mechanisms which is reflected in our model of implementation of palliative care practices through a learning collaborative. These findings suggest that the implementation of complex practices such as palliative care may be more successful through iterative learning and practice opportunities as the mechanisms for change are layered and mutually reinforcing.ClinicalTrials.gov, NCT04125537 . Registered 14 October 2019 - Retrospectively registered.

  View details for DOI 10.1186/s12913-023-10360-7

  View details for PubMedID 38082293

  View details for PubMedCentralID PMC10712060

• Using Relative Survival to Estimate the Burden of Kidney Failure. American journal of kidney diseases : the official journal of the National Kidney Foundation Stedman, M. R., Tamura, M. K., Chertow, G. M. 2023

  Abstract

  Estimates of mortality from kidney failure are misleading because the mortality from kidney failure is inseparable from the mortality attributed to comorbid conditions. We sought to develop an alternative method to reduce the bias in estimating mortality due to kidney failure using life table methods.Longitudinal cohort study.Using data from the United States Renal Data System and the Medicare 5% sample, we identified an incident cohort of patients, age 66+, who first had kidney failure in 2009 and a similar general population cohort without kidney failure.Kidney failure.Death.We created comorbidity, age, sex, race, and year-specific life tables to estimate relative survival of patients with incident kidney failure and to attain an estimate of excess kidney failure-related deaths. Estimates were compared with those based on standard life tables (not adjusted for comorbidity).The analysis included 31,944 adults with kidney failure with a mean age of 77 +/- 7 years. 5-year relative survival was 31% using standard life tables (adjusted for age, sex, race, and year) versus 36% using life tables also adjusted for comorbidities. Compared with other chronic diseases, patients with kidney failure have among the lowest relative survival. Patients with incident kidney failure ages 66-70 and 76-80 have a survival comparable to adults without kidney failure roughly 86-90 and 91-95 years old, respectively.Relative survival estimates can be improved by narrowing the specificity of the covariates collected, (e.g. disease severity and ethnicity).Estimates of survival relative to a matched general population partition the mortality due to kidney failure from other causes of death. Results highlight the immense burden of kidney failure on mortality and the importance of disease prevention efforts among older adults.

  View details for DOI 10.1053/j.ajkd.2023.05.015

  View details for PubMedID 37678740

• Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes. JAMA internal medicine Cheng, X. S., Liu, S., Han, J., Stedman, M. R., Baiocchi, M., Tan, J. C., Chertow, G. M., Fearon, W. F. 2023

  Abstract

  Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear.Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI).Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes.Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant.Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant.Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P<.001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%).Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

  View details for DOI 10.1001/jamainternmed.2022.6069

  View details for PubMedID 36595271

• Advice for isolated statisticians collaborating in academic healthcare centre settings STAT Mehta, C., Stedman, M. R., Rao, S. R., Podolsky, R. 2022; 11 (1)

  View details for DOI 10.1002/sta4.492

  View details for Web of Science ID 000887550500001

• National Imaging Trends for Suspected Urinary Stone Disease in the Emergency Department. JAMA internal medicine Ganesan, C., Stedman, M. R., Liu, S., Conti, S. L., Chertow, G. M., Leppert, J. T., Pao, A. C. 2022

  View details for DOI 10.1001/jamainternmed.2022.4939

  View details for PubMedID 36315134

• APOL1 G3 Variant Is Associated with Cardiovascular Mortality and Sudden Cardiac Death in Patients Receiving Maintenance Hemodialysis of European Ancestry. Cardiorenal medicine Schwantes-An, T., Robinson-Cohen, C., Liu, S., Zheng, N., Stedman, M., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2022: 1-7

  Abstract

  INTRODUCTION: The G1 and G2 variants in the APOL1 gene convey high risk for the progression of chronic kidney disease in African Americans. The G3 variant in APOL1 is more common in patients of European ancestry (EA); outcomes associated with this variant have not been explored previously in EA patients receiving dialysis.METHODS: DNA was collected from approximately half of the patients enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial and genotyped for the G3 variants. We utilized an additive genetic model to test associations of G3 with the EVOLVE adjudicated endpoints of all-cause mortality, cardiovascular mortality, sudden cardiac death (SCD), and heart failure. EA and African ancestry samples were analyzed separately. Validation was done in the Vanderbilt BioVU using ICD codes for cardiovascular events that parallel the adjudicated endpoints in EVOLVE.RESULTS: In EVOLVE, G3 in EA patients was associated with the adjudicated endpoints of cardiovascular mortality and SCD. In a validation cohort from the Vanderbilt BioVU, cardiovascular events and cardiovascular mortality defined by ICD codes showed similar associations in EA participants who had been on dialysis for 2 to <5 years.DISCUSSION/CONCLUSIONS: G3 in APOL1 variant was associated with cardiovascular events and cardiovascular mortality in the EA patients receiving dialysis. This suggests that variations in the APOL1 gene that differ in populations of different ancestry may contribute to cardiovascular disease.

  View details for DOI 10.1159/000525448

  View details for PubMedID 36310009

• Testosterone concentrations andoutcomes in hemodialysis patients of the EVOLVE trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Nilsson, E., Stenvinkel, P., Liu, S., Stedman, M. R., Chertow, G. M., Floege, J. 2022

  Abstract

  Hypogonadism is common in end-stage kidney disease and may contribute to morbidity and mortality.Using data from the randomized controlled EVOLVE trial of cinacalcet, we analyzed the associations of total testosterone, free testosterone, and sex-hormone binding globulin (SHBG) serum concentrations with mortality and major cardiovascular events in 1692 men and 1059 women receiving hemodialysis. We also describe the effect of cinacalcet treatment on serum concentrations of testosterone.Among men, lower serum free testosterone (OR 0.18 95%, CI 0.04-0.82, p = 0.026) and higher SHBG (OR 1.05 per 10 nmol/L, 95% CI 1.01-1.10, p = 0.012), but not total testosterone, were associated with higher risk of death or cardiovascular event. Only SHBG was associated with all-cause mortality (OR 1.07 per 10 nmol/L, 95% CI 1.02-1.12, p = 0.0073). Among women, neither total- or free testosterone, nor SHBG were associated with outcomes. We found no statistically significant effect of cinacalcet treatment on SHBG, free- or total testosterone.Lower free testosterone and higher SHBG in serum are associated with higher risk of death or cardiovascular event in men undergoing chronic hemodialysis.

  View details for DOI 10.1093/ndt/gfac278

  View details for PubMedID 36175142

• Implementation and Effectiveness of a Learning Collaborative to Improve Palliative Care for Seriously Ill Hemodialysis Patients. Clinical journal of the American Society of Nephrology : CJASN Kurella Tamura, M., Holdsworth, L., Stedman, M., Aldous, A., Asch, S. M., Han, J., Harbert, G., Lorenz, K. A., Malcolm, E., Nicklas, A., Moss, A. H., Lupu, D. E. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: Limited implementation of palliative care practices in hemodialysis may contribute to end-of-life care that is intensive and not patient centered. We determined whether a learning collaborative for hemodialysis center providers improved delivery of palliative care best practices.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ten US hemodialysis centers participated in a pre-post study targeting seriously ill patients between April 2019 and September 2020. Three practices were prioritized: screening for serious illness, goals of care discussions, and use of a palliative dialysis care pathway. The collaborative educational bundle consisted of learning sessions, communication skills training, and implementation support. The primary outcome was change in the probability of complete advance care planning documentation among seriously ill patients. Health care utilization was a secondary outcome, and implementation outcomes of acceptability, adoption, feasibility, and penetration were assessed using mixed methods.RESULTS: One center dropped out due to the coronavirus disease 2019 pandemic. Among the remaining nine centers, 20% (273 of 1395) of patients were identified as seriously ill preimplementation, and 16% (203 of 1254) were identified as seriously ill postimplementation. From the preimplementation to postimplementation period, the adjusted probability of complete advance care planning documentation among seriously ill patients increased by 34.5 percentage points (95% confidence interval, 4.4 to 68.5). There was no difference in mortality or in utilization of palliative hemodialysis, hospice referral, or hemodialysis discontinuation. Screening for serious illness was widely adopted, and goals of care discussions were adopted with incomplete integration. There was limited adoption of a palliative dialysis care pathway.CONCLUSIONS: A learning collaborative for hemodialysis centers spanning the coronavirus disease 2019 pandemic was associated with adoption of serious illness screening and goals of care discussions as well as improved documentation of advance care planning for seriously ill patients.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Pathways Project: Kidney Supportive Care, NCT04125537.

  View details for DOI 10.2215/CJN.00090122

  View details for PubMedID 36104084

• Trends in Coronary Artery Disease Screening before Kidney Transplantation. Kidney360 Cheng, X. S., Liu, S., Han, J., Stedman, M. R., Chertow, G. M., Tan, J. C., Fearon, W. F. 2022; 3 (3): 516-523

  Abstract

  Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States.Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant.Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods.Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

  View details for DOI 10.34067/KID.0005282021

  View details for PubMedID 35582172

• Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States. Clinical journal of the American Society of Nephrology : CJASN Krissberg, J., Kaufmann, M., Gupta, A., Bendavid, E., Stedman, M., Cheng, X., Tan, J., Grimm, P., Chaudhuri, A. 2021

  Abstract

  Background and Objectives: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial/ethnic disparities in pediatric kidney transplantation access and related outcomes. Design, setting, participants, and measurements: A retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients. Log-logistic accelerated failure time models were used to determine time from first activation on the transplant list and time on dialysis to deceased-donor transplant, each with KAS era or race/ethnicity as the exposure of interest. We used logistic regression to assess odds of delayed graft function. Log-rank tests assessed time to graft loss within racial/ethnic groups across KAS eras. Results: All children experienced longer wait times from activation to transplantation post-KAS. In univariable analysis, Black or Hispanic children or other children of color experienced longer times from activation to transplant compared to White children in the both eras; this finding was largely attenuated after multivariable analysis (time ratio 1.16, (95% CI 1.01-1.32); 1.13 (1.00-1.28); 1.17 (0.96-1.41) post-KAS, respectively). Multivariable analysis also showed that racial/ethnic disparities in time from dialysis initiation to transplantation in the pre-KAS era was mitigated in the post-KAS era. There were no disparities in odds of delayed graft function. Black or Hispanic children experienced longer times with a functioning graft in the post-KAS era. Conclusions: No racial/ethnic disparities from activation to deceased donor transplantation were seen before or after implementation of KAS in multivariable analysis, while time on dialysis to transplantation and odds of short-term graft loss improved in equity after KAS, without compromising disparities in delayed graft function.

  View details for DOI 10.2215/CJN.06740521

  View details for PubMedID 34670797

• Intensive Blood Pressure Control and Diabetes Mellitus-Related Limb Events in Patients With Type 2 Diabetes Mellitus: Reanalysis of ACCORD. Journal of the American Heart Association Tran, K., Stedman, M., Chang, T. I. 2021: e021407

  View details for DOI 10.1161/JAHA.121.021407

  View details for PubMedID 34320842

• Karnofsky Performance Score-Failure to Thrive as a Frailty Proxy? Transplantation direct Stedman, M. R., Watford, D. J., Chertow, G. M., Tan, J. C. 2021; 7 (7): e708

  Abstract

  Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility.Methods: We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist.Results: Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2-7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20-80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score.Conclusions: The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.

  View details for DOI 10.1097/TXD.0000000000001164

  View details for PubMedID 34124344

• Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates. Cardiorenal medicine Cheng, X. S., Watford, D. J., Arashi, H., Stedman, M. R., Chertow, G. M., Tan, J. C., Fearon, W. F. 2021: 1-11

  Abstract

  INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions.OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting.METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events.RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m).CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

  View details for DOI 10.1159/000516158

  View details for PubMedID 34034263

• And Then There Were Three: Effects of Pretransplant Dialysis on Multiorgan Transplantation. Transplantation direct Cheng, X. S., Han, J., Stedman, M. R., Chertow, G. M., Tan, J. C. 2021; 7 (2): e657

  Abstract

  Background: Simultaneous liver-kidney (SLK) and simultaneous heart-kidney (SHK) transplantation currently utilize 6% of deceased donor kidneys in the United States. To what extent residual kidney function accounts for apparent kidney allograft survival is unknown.Methods: We examined all adult SLK and SHK transplants in the United States during 1995-2014. We considered the duration of dialysis preceding SLK or SHK (≥90 d, 1-89 d, or none) as a proxy of residual kidney function. We used multinomial logistic regression to estimate the difference in the adjusted likelihood of 6- and 12-month apparent kidney allograft failure between the no dialysis versus ≥90 days dialysis groups.Results: Of 4875 SLK and 848 SHK recipients, 1775 (36%) SLK and 449 (53%) SHK recipients received no dialysis before transplant. The likelihood of apparent kidney allograft failure was 1%-3% lower at 12 months in SLK and SHK recipients who did not require pretransplant dialysis relative to recipients who required ≥90 days of pretransplant dialysis. Among 3978 SLK recipients who survived to 1 year, no pretransplant dialysis was associated with a lower risk of apparent kidney allograft failure over a median follow-up of 5.7 years (adjusted hazard ratio 0.73 [0.55-0.96]).Conclusions: Patients with residual kidney function at the time of multiorgan transplantation are less likely to have apparent failure of the kidney allograft. Whether residual kidney function facilitates function of the allograft or whether some SLK and SHK recipients have 3 functional kidneys is unknown. Sustained kidney function after SLK and SHK transplants does not necessarily indicate successful MOT.

  View details for DOI 10.1097/TXD.0000000000001112

  View details for PubMedID 33490382

• Documentation of Reproductive Health Counseling Among Women With CKD: A Retrospective Chart Review. American journal of kidney diseases : the official journal of the National Kidney Foundation Okundaye, I. O., Stedman, M. R., Rhee, J. J., O'Shaughnessy, M., Lafayette, R. A. 2021

  View details for DOI 10.1053/j.ajkd.2021.08.012

  View details for PubMedID 34571063

• Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT). Hypertension (Dallas, Tex. : 1979) Wang, K. M., Stedman, M. R., Chertow, G. M., Chang, T. I. 2020: HYPERTENSIONAHA12016155

  Abstract

  SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.

  View details for DOI 10.1161/HYPERTENSIONAHA.120.16155

  View details for PubMedID 33131314

• Screening Rates for Primary Aldosteronism in Resistant Hypertension: A Cohort Study. Hypertension (Dallas, Tex. : 1979) Jaffe, G., Gray, Z., Krishnan, G., Stedman, M., Zheng, Y., Han, J., Chertow, G. M., Leppert, J. T., Bhalla, V. 2020: HYPERTENSIONAHA11914359

  Abstract

  Resistant hypertension is associated with higher rates of cardiovascular disease, kidney disease, and death than primary hypertension. Although clinical practice guidelines recommend screening for primary aldosteronism among persons with resistant hypertension, rates of screening are unknown. We identified 145 670 persons with hypertension and excluded persons with congestive heart failure or advanced chronic kidney disease. Among this cohort, we studied 4660 persons ages 18 to <90 from the years 2008 to 2014 with resistant hypertension and available laboratory tests within the following 24 months. The screening rate for primary aldosteronism in persons with resistant hypertension was 2.1%. Screened persons were younger (55.9±13.3 versus 65.5±11.6 years; P<0.0001) and had higher systolic (145.1±24.3 versus 139.6±20.5 mm Hg; P=0.04) and diastolic blood pressure (81.8±13.6 versus 74.4±13.8 mm Hg; P<0.0001), lower rates of coronary artery disease (5.2% versus 14.2%; P=0.01), and lower serum potassium concentrations (3.9±0.6 versus 4.1±0.5 mmol/L; P=0.04) than unscreened persons. Screened persons had significantly higher rates of prescription for calcium channel blockers, mixed alpha/beta-adrenergic receptor antagonists, sympatholytics, and vasodilators, and lower rates of prescription for loop, thiazide, and thiazide-type diuretics. The prescription of mineralocorticoid receptor antagonists or other potassium-sparing diuretics was not significantly different between groups (P=0.20). In conclusion, only 2.1% of eligible persons received a screening test within 2 years of meeting criteria for resistant hypertension. Low rates of screening were not due to the prescription of antihypertensive medications that may potentially interfere with interpretation of the screening test. Efforts to highlight guideline-recommended screening and targeted therapy are warranted.

  View details for DOI 10.1161/HYPERTENSIONAHA.119.14359

  View details for PubMedID 32008436

• Physical Performance Testing in Kidney Transplant Candidates at the Top of the Waitlist. American journal of kidney diseases : the official journal of the National Kidney Foundation Cheng, X. S., Myers, J. n., Han, J. n., Stedman, M. R., Watford, D. J., Lee, J. n., Discipulo, K. V., Chan, K. N., Chertow, G. M., Tan, J. C. 2020

  Abstract

  Frailty and poor physical function are associated with adverse kidney transplant outcomes, but how to incorporate this knowledge into clinical practice is uncertain. We studied the association between measured physical performance and clinical outcomes among patients on kidney transplant waitlists.Prospective observational cohort study.We studied consecutive patients evaluated in our Transplant Readiness Assessment Clinic, a top-of-the-waitlist management program, from May 2017 through December 2018 (N=305). We incorporated physical performance testing, including the 6-minute walk test (6MWT) and the sit-to-stand (STS) test, into routine clinical assessments.6MWT and STS test results.Primary - Time to adverse waitlist outcomes (removal from waitlist or death). Secondary - Time to transplantation, time to death.We used linear regression to examine the relationship between clinical characteristics and physical performance test results. We used subdistribution hazards models to examine the association between physical performance test results and outcomes.Median 6MWT and STS results were 393 meters (25th- 75th percentile range 305-455) and 17 repetitions (25th- 75th percentile range 12-21), respectively. Clinical characteristics and Estimated Post-Transplant Survival scores only accounted for 14-21% of the variance in 6MWT/STS results. 6MWT/STS results were associated with adverse waitlist outcomes (adjusted subdistribution hazard ratio [sHR] of 1.42 [95% confidence interval 1.30-1.56 per 50-meter lower in 6MWT and 1.53 [95% confidence interval 1.33-1.75] per 5-repetition lower in STS), and with transplantation (adjusted sHR of 0.80 [95% confidence interval 0.72-0.88] per 50-meter lower in 6MWT and 0.80 [95% confidence interval 0.71-0.89] per 5-repetition lower in STS). Addition of either STS or 6MWT to survival models containing clinical characteristics enhanced fit (likelihood ratio test p<0.001).Single-center observational study. Other measures of global health status (e.g., Fried frailty index or short physical performance battery) were not examined.Among waitlisted kidney transplant candidates with high Kidney Allocation Scores, standardized and easily performed physical performance test results are associated with waitlist outcomes and contain information beyond what is currently routinely collected in clinical practice.

  View details for DOI 10.1053/j.ajkd.2020.04.009

  View details for PubMedID 32512039

• Toward telemedicine-compatible physical functioning assessments in kidney transplant candidates. Clinical transplantation Watford, D. J., Cheng, X. S., Han, J. n., Stedman, M. R., Chertow, G. M., Tan, J. C. 2020: e14173

  Abstract

  Frailty is associated with adverse kidney transplant outcomes and can be assessed by subjective and objective metrics. There is increasing recognition of the value of metrics obtainable remotely. We compared the self-reported SF-36 physical functioning subscale score (SF-36 PF) with in-person physical performance tests (6-minute walk and sit-to-stand) in a prospective cohort of kidney transplant candidates. We assessed each metric's ability to predict time to the composite outcome of waitlist removal or death, censoring at transplant. We built time-dependent receiver operating characteristic curves and calculated the area under the curve [AUC(t)] at 1 year, using bootstrapping for internal validation. In 199 patients followed for a median of 346 days, 41 reached the composite endpoint. Lower SF-36 PF scores were associated with higher risk of waitlist removal/death, with every 10-point decrease corresponding to a 16% increase in risk. All models showed an AUC(t) of 0.83-0.84 that did not contract substantially after internal validation. Among kidney transplant candidates, SF-36 PF, obtainable remotely, can help to stratify the risk of waitlist removal or death, and may be used as a screening tool for poor physical functioning in ongoing candidate evaluation, particularly where travel, increasing patient volume, or other restrictions challenge in-person assessment.

  View details for DOI 10.1111/ctr.14173

  View details for PubMedID 33247983

• Impact of Pretransplant Donor BK Viruria in Kidney Transplant Recipients JOURNAL OF INFECTIOUS DISEASES Tan, S. K., Huang, C., Sahoo, M. K., Weber, J., Kurzer, J., Stedman, M. R., Concepcion, W., Gallo, A. E., Alonso, D., Srinivas, T., Storch, G. A., Subramanian, A. K., Tan, J. C., Pinsky, B. A. 2019; 220 (3): 370–76

  View details for DOI 10.1093/infdis/jiz114

  View details for Web of Science ID 000477595700005

• Impact of Pre-Transplant Donor BK Viruria in Kidney Transplant Recipients. The Journal of infectious diseases Tan, S. K., Huang, C., Sahoo, M. K., Weber, J., Kurzer, J., Stedman, M. R., Concepcion, W., Gallo, A. E., Alonso, D., Srinivas, T., Storch, G. A., Subramanian, A. K., Tan, J. C., Pinsky, B. A. 2019

  Abstract

  BACKGROUND: BK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients.METHODS: We prospectively collected pre-transplant plasma and urine samples from living and deceased kidney donors and performed BKV PCR and IgG testing on pre-transplant and serially collected post-transplant samples in kidney transplant recipients.RESULTS: Among deceased donors, 8.1%(17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4%(6/39) of living donors and 8.5%(4/47) of deceased donors of recipients at our institution (p=0.50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6%vs.7.8%, p<0.001) and viremia (66.6%vs.8.9%, p<0.001) with a shorter time to onset (log-rank, p<0.001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pre-transplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (p=0.31,0.75,0.51,respectively).DISCUSSION: Donor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at-risk for BKV complications.

  View details for PubMedID 30869132

• Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stubbs, J. R., Stedman, M. R., Liu, S., Long, J., Franchetti, Y., West, R. E., Prokopienko, A. J., Mahnken, J. D., Chertow, G. M., Nolin, T. D. 2019; 14 (2): 261–67

  View details for DOI 10.2215/CJN.06190518

  View details for Web of Science ID 000458400200015

• Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis. American journal of nephrology Schwantes-An, T., Liu, S., Stedman, M., Decker, B. S., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2019; 49 (2): 125–32

  Abstract

  BACKGROUND: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis.OBJECTIVES: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality.METHODS: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest.RESULTS: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest.CONCLUSIONS: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.

  View details for PubMedID 30669147

• Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with End-stage Kidney Disease Receiving Maintenance Hemodialysis. Clinical journal of the American Society of Nephrology : CJASN Stubbs, J. R., Stedman, M. R., Liu, S., Long, J., Franchetti, Y., West, R. E., Prokopienko, A. J., Mahnken, J. D., Chertow, G. M., Nolin, T. D. 2019

  Abstract

  BACKGROUND AND OBJECTIVES: Trimethylamine N-oxide (TMAO), a compound derived from byproducts of intestinal bacteria, has been shown to accelerate atherosclerosis in rodents. To date, there are conflicting data regarding the association of serum TMAO with cardiovascular outcomes in patients with ESKD, a population exhibiting both high serum TMAO and excessive atherosclerosis.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured baseline serum TMAO concentrations in a subset of participants (n=1243) from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial and conducted post hoc analyses evaluating the association between baseline serum TMAO and cardiovascular outcomes.RESULTS: We observed a wide distribution of serum TMAO in our cohort, with approximately 80% of participants exhibiting TMAO concentrations ≥56 M and a maximum TMAO concentration of 1103.1 M. We found no association between TMAO and our primary outcome, a composite of cardiovascular mortality, myocardial infarction, peripheral vascular event, stroke, and hospitalization for unstable angina. Moreover, in unadjusted and adjusted analyses, we observed no relation between TMAO and all-cause mortality, the independent components of our composite outcome, or the original EVOLVE primary outcome. Although we did observe higher TMAO concentrations in white participants, further subgroup analyses did not confirm the previously identified interaction between TMAO and race observed in a prior study in patients receiving dialysis.CONCLUSIONS: We found no evidence linking TMAO to adverse clinical outcomes in patients receiving maintenance hemodialysis with moderate to severe secondary hyperparathyroidism.

  View details for PubMedID 30665924

• Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis AMERICAN JOURNAL OF NEPHROLOGY Schwantes-An, T., Liu, S., Stedman, M., Decker, B. S., Wetherill, L., Edenberg, H. J., Vatta, M., Foroud, T. M., Chertow, G. M., Moe, S. M. 2019; 49 (2): 125–32

  View details for DOI 10.1159/000496060

  View details for Web of Science ID 000459402800005

• Longitudinal Changes in Kidney Function Following Heart Transplantation: Stanford Experience. Clinical transplantation Taiwo, A., Khush, K., Stedman, M. R., Zheng, Y., Tan, J. C. 2018: e13414

  Abstract

  Many heart transplant recipients experience declining kidney function following transplantation. We aimed toquantify change in kidney function in heart transplant recipients stratified by pre-transplant kidney function. 230 adult heart transplant recipients between May 1, 2008 and December 31, 2014 were evaluated for up to 5 years post-transplant (median 1 year). Using 19,398 total eGFR assessments, we evaluated trends in estimated glomerular filtration rate (eGFR) in recipients with normal/near normal (eGFR >45 mL/min/1.73m2 ) versus impaired (eGFR <45 mL/min/1.73m2 ) kidney function and the likelihood of reaching an eGFR of 20 mL/min/1.73m2 after heart transplant. Baseline characteristics were similar. Immediately following heart transplant, the impaired pre-transplant kidney function group showed a mean eGFR gain of 9.5mL/min/1.73m2 (n=193) versus a mean decline of 4.9 mL/min/1.73m2 (n=37) in the normal/near normal group. Subsequent rates of eGFR decline were 2.2 mL/min/1.73m2 /yrversus2.9 mL/min/1.73m2 /yr, respectively. The probability of reaching an eGFR of 20 mL/min/1.73m2 or less at 1, 5, and 10 years following heart transplant was 1%, 4% and 30% in the impaired group, and <1%, <1%, and 10% in the normal/near normal group. Estimates of expected recovery in kidney function and its decline over time will help inform decision making about kidney care after heart transplantation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.13414

  View details for PubMedID 30240515

• Education in consultation: A comparative survey-based assessment of perceived educational effectiveness within a university and community-based internal medicine residency. MedEdPublish (2016) Rope, R., Merrell, S. B., Stedman, M., Young, B. 2017; 6: 153

  Abstract

  This article was migrated. The article was marked as recommended. Background: Education in consultation is a potentially valuable, but understudied, element of medical education. Inpatient consultation is an opportunity for significant subspecialist contact for resident trainees and an avenue for improving their knowledge and patient care across content areas. We evaluated the perceived educational effectiveness of education in consultation among internal medicine residents, within a university and a community-based program, as well as the role of barriers in medical training that may limit education. Methods: We used a web-based survey expanded from a previously published survey consisting of 12 questions, including one free-response, on education in consultation. Data were analyzed descriptively and qualitatively. We surveyed residents from two internal medicine programs in 2016. One within a large university-based hospital and the second within a smaller community-based safety-net hospital. Results: 91/198 (46%) of residents responded. Overall results from both programs were similar despite their structural differences. Residents viewed education in consultation as a priority and the majority felt it was at least moderately effective but underutilized. Importantly, educational interactions are largely dependent on outreach from residents. While in-person teaching interactions were the most effective, key barriers to these interactions include a lack of time, difficulty locating residents, and the perception of residents as being too busy. Conclusions: Inpatient consultation offers a unique opportunity for specialist-led education for internal medicine residents. It is potentially effective but constrained extensively in modern training environments. Interventions aimed at emphasizing education in consultation within fellowships and residencies, increasing in-person resident-specialist interactions, and addressing structural barriers, may improve resident knowledge across specialties and strengthen patient care.

  View details for DOI 10.15694/mep.2017.000153

  View details for PubMedID 38406436

  View details for PubMedCentralID PMC10885288

• Screening Rates for the Diagnostic Workup of Resistant Hypertension Jaffe, G. M., Krishnan, G., Stedman, M., Chertow, G. M., Leppert, J. T., Bhalla, V. LIPPINCOTT WILLIAMS & WILKINS. 2017

  View details for Web of Science ID 000523486000196

• Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation TRANSPLANTATION Cheng, X. S., Stedman, M. R., Chertow, G. M., Kim, W. R., Tan, J. C. 2017; 101 (5): 1111-1119

  Abstract

  Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

  View details for DOI 10.1097/TP.0000000000001491

  View details for PubMedID 28437790

• Current estimates of the cure fraction: a feasibility study of statistical cure for breast and colorectal cancer. Journal of the National Cancer Institute. Monographs Stedman, M. R., Feuer, E. J., Mariotto, A. B. 2014; 2014 (49): 244-254

  Abstract

  The probability of cure is a long-term prognostic measure of cancer survival. Estimates of the cure fraction, the proportion of patients "cured" of the disease, are based on extrapolating survival models beyond the range of data. The objective of this work is to evaluate the sensitivity of cure fraction estimates to model choice and study design.Data were obtained from the Surveillance, Epidemiology, and End Results (SEER)-9 registries to construct a cohort of breast and colorectal cancer patients diagnosed from 1975 to 1985. In a sensitivity analysis, cure fraction estimates are compared from different study designs with short- and long-term follow-up. Methods tested include: cause-specific and relative survival, parametric mixture, and flexible models. In a separate analysis, estimates are projected for 2008 diagnoses using study designs including the full cohort (1975-2008 diagnoses) and restricted to recent diagnoses (1998-2008) with follow-up to 2009.We show that flexible models often provide higher estimates of the cure fraction compared to parametric mixture models. Log normal models generate lower estimates than Weibull parametric models. In general, 12 years is enough follow-up time to estimate the cure fraction for regional and distant stage colorectal cancer but not for breast cancer. 2008 colorectal cure projections show a 15% increase in the cure fraction since 1985.Estimates of the cure fraction are model and study design dependent. It is best to compare results from multiple models and examine model fit to determine the reliability of the estimate. Early-stage cancers are sensitive to survival type and follow-up time because of their longer survival. More flexible models are susceptible to slight fluctuations in the shape of the survival curve which can influence the stability of the estimate; however, stability may be improved by lengthening follow-up and restricting the cohort to reduce heterogeneity in the data.

  View details for DOI 10.1093/jncimonographs/lgu015

  View details for PubMedID 25417238

• Adolescent and young adult cancer survival. Journal of the National Cancer Institute. Monographs Lewis, D. R., Seibel, N. L., Smith, A. W., Stedman, M. R. 2014; 2014 (49): 228-235

  Abstract

  Adolescent and young adults (AYAs) face challenges in having their cancers recognized, diagnosed, treated, and monitored. Monitoring AYA cancer survival is of interest because of the lack of improvement in outcome previously documented for these patients as compared with younger and older patient outcomes. AYA patients 15-39 years old, diagnosed during 2000-2008 with malignant cancers were selected from the SEER 17 registries data. Selected cancers were analyzed for incidence and five-year relative survival by histology, stage, and receptor subtypes. Hazard ratios were estimated for cancer death risk among younger and older ages relative to the AYA group. AYA survival was worse for female breast cancer (regardless of estrogen receptor status), acute lymphoid leukemia (ALL), and acute myeloid leukemia (AML). AYA survival for AML was lowest for a subtype associated with a mutation of the nucleophosmin 1 gene (NPM1). AYA survival for breast cancer and leukemia remain poor as compared with younger and older survivors. Research is needed to address disparities and improve survival in this age group.

  View details for DOI 10.1093/jncimonographs/lgu019

  View details for PubMedID 25417236

  View details for PubMedCentralID PMC4841167

• A comparison of statistical approaches for physician-randomized trials with survival outcomes CONTEMPORARY CLINICAL TRIALS Stedman, M. R., Lew, R. A., Losina, E., Gagnon, D. R., Solomon, D. H., Brookhart, M. A. 2012; 33 (1): 104-115

  Abstract

  This study compares methods for analyzing correlated survival data from physician-randomized trials of health care quality improvement interventions. Several proposed methods adjust for correlated survival data; however the most suitable method is unknown. Applying the characteristics of our study example, we performed three simulation studies to compare conditional, marginal, and non-parametric methods for analyzing clustered survival data. We simulated 1000 datasets using a shared frailty model with (1) fixed cluster size, (2) variable cluster size, and (3) non-lognormal random effects. Methods of analyses included: the nonlinear mixed model (conditional), the marginal proportional hazards model with robust standard errors, the clustered logrank test, and the clustered permutation test (non-parametric). For each method considered we estimated Type I error, power, mean squared error, and the coverage probability of the treatment effect estimator. We observed underestimated Type I error for the clustered logrank test. The marginal proportional hazards method performed well even when model assumptions were violated. Nonlinear mixed models were only advantageous when the distribution was correctly specified.

  View details for DOI 10.1016/j.cct.2011.08.008

  View details for Web of Science ID 000300072500018

  View details for PubMedID 21924382

• Meta-analyses involving cross-over trials: methodological issues INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Stedman, M. R., Curtin, F., Elbourne, D. R., Kesselheim, A. S., Brookhart, M. A. 2011; 40 (6): 1732-1734

  View details for DOI 10.1093/ije/dyp345

  View details for Web of Science ID 000297868500037

  View details for PubMedID 20026595

• A SAS macro for a clustered logrank test COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE Stedman, M. R., Gagnon, D. R., Lew, R. A., Jung, S., Losina, E., Brookhart, M. A. 2011; 104 (2): 266-270

  Abstract

  The clustered logrank test is a nonparametric method of significance testing for correlated survival data. Examples of its application include cluster randomized trials where groups of patients rather than individuals are randomized to either a treatment or a control intervention. We describe a SAS macro that implements the 2-sample clustered logrank test for data where the entire cluster is randomized to the same treatment group. We discuss the theory and applications behind this test as well as details of the SAS code.

  View details for DOI 10.1016/j.cmpb.2011.02.001

  View details for Web of Science ID 000296945100031

  View details for PubMedID 21496938

• Guideline-conformity of initiation with oral hypoglycemic treatment for patients with newly therapy-dependent type 2 diabetes mellitus in Austria PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Winkelmayer, W. C., Stedman, M. R., Pogantsch, M., Wieninger, P., Bucsics, A., Asslaber, M., Bauer, R., Burkhardt, T., Schautzer, A., Brookhart, M. A. 2011; 20 (1): 57-65

  Abstract

  To determine guideline conformity of initiation of oral hypoglycemic (OH) treatment for type 2 diabetes in Austria; to study patient and prescriber correlates of recommended initiation with metformin monotherapy.We used claims from 11 sickness funds that covered 7.5 million individuals, representing >90% of the Austrian population. First-time OH use was defined as a first filled prescription after one year without any OH drug or insulin. Among these incident users, we described the OH drug class used and defined correlates of initiation with metformin monotherapy.From 1/2007 to 6/2008, we identified 42,882 incident users of an OH drug: 70.8% used metformin, 24.7% used a sulfonylurea, and 4.5% initiated treatment with another class. We estimated the incidence of OH-dependent type 2 diabetes at 3.8-4.4 per 1000 patient-years. We conducted multivariate analyses among 39 077 patients with available prescriber information. Independent correlates of initiation with metformin were younger age, female gender, waived co-payment, more recent initiation, fewer hospital days and more therapeutic classes received in the year prior to first OH therapy (all p < 0.001). Prescriber specialty and age (p < 0.001), but not gender, were also associated with metformin initiation. Approximately 20% of metformin initiators had a second OH drug added within <18 months. While we were unable to ascertain specific contraindications to metformin (renal insufficiency, hepatic failure), <10% of the general population are expected to have these conditions.Seventy per cent of new initiators of OH treatment in Austria received metformin as recommended by international guidelines. At least 20% did not, taking into account possible contraindications, which provides an opportunity for intervention.

  View details for DOI 10.1002/pds.2059

  View details for Web of Science ID 000286071700008

  View details for PubMedID 21182153

• Evaluation of Guideline-Conformity of Initiation of Oral Hypoglycemic Treatment for Incident Diabetes Mellitus Type 2 in Austria Winkelmayer, W. C., Stedman, M. R., Pogantsch, M., Wieninger, P., Bucsics, A., Brookhart, A. WILEY-BLACKWELL. 2010: S54

  View details for Web of Science ID 000209826200123

• Primary Medication Non-Adherence: Analysis of 195,930 Electronic Prescriptions JOURNAL OF GENERAL INTERNAL MEDICINE Fischer, M. A., Stedman, M. R., Lii, J., Vogeli, C., Shrank, W. H., Brookhart, M. A., Weissman, J. S. 2010; 25 (4): 284-290

  Abstract

  Non-adherence to essential medications represents an important public health problem. Little is known about the frequency with which patients fail to fill prescriptions when new medications are started ("primary non-adherence") or predictors of failure to fill.Evaluate primary non-adherence in community-based practices and identify predictors of non-adherence.75,589 patients treated by 1,217 prescribers in the first year of a community-based e-prescribing initiative.We compiled all e-prescriptions written over a 12-month period and used filled claims to identify filled prescriptions. We calculated primary adherence and non-adherence rates for all e-prescriptions and for new medication starts and compared the rates across patient and medication characteristics. Using multivariable regressions analyses, we examined which characteristics were associated with non-adherence.Primary medication non-adherence.Of 195,930 e-prescriptions, 151,837 (78%) were filled. Of 82,245 e-prescriptions for new medications, 58,984 (72%) were filled. Primary adherence rates were higher for prescriptions written by primary care specialists, especially pediatricians (84%). Patients aged 18 and younger filled prescriptions at the highest rate (87%). In multivariate analyses, medication class was the strongest predictor of adherence, and non-adherence was common for newly prescribed medications treating chronic conditions such as hypertension (28.4%), hyperlipidemia (28.2%), and diabetes (31.4%).Many e-prescriptions were not filled. Previous studies of medication non-adherence failed to capture these prescriptions. Efforts to increase primary adherence could dramatically improve the effectiveness of medication therapy. Interventions that target specific medication classes may be most effective.

  View details for DOI 10.1007/s11606-010-1253-9

  View details for Web of Science ID 000275779300003

  View details for PubMedID 20131023

• A SAS macro for a clustered permutation test COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE Stedman, M. R., Gagnon, D. R., Lew, R. A., Solomon, D. H., Losina, E., Brookhart, M. A. 2009; 95 (1): 89-94

  Abstract

  The clustered permutation test is a nonparametric method of significance testing for correlated data. It is often used in cluster randomized trials where groups of patients rather than individuals are randomized to either a treatment or control intervention. We describe a flexible and efficient SAS macro that implements the 2-sample clustered permutation test. We discuss the theory and applications behind this test as well as details of the SAS code.

  View details for DOI 10.1016/j.cmpb.2009.02.005

  View details for Web of Science ID 000266187900008

  View details for PubMedID 19321221

• The Relationship Between Focal Erosions and Generalized Osteoporosis in Postmenopausal Women With Rheumatoid Arthritis ARTHRITIS AND RHEUMATISM Solomon, D. H., Finkelstein, J. S., Shadick, N., LeBoff, M. S., Winalski, C. S., Stedman, M., Glass, R., Brookhart, M. A., Weinblatt, M. E., Gravallese, E. M. 2009; 60 (6): 1624-1631

  Abstract

  Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA.We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models.Patients had an average disease duration of 13.7 years, and almost all were taking a disease-modifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r=-0.33, P<0.0001), but not with lumbar spine BMD (r=-0.09, P=0.27). Hip BMD was significantly lower in RF-positive patients versus RF-negative patients (P=0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions.Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors.

  View details for DOI 10.1002/art.24551

  View details for Web of Science ID 000267116800010

  View details for PubMedID 19479876

• An evaluation of statistical approaches for analyzing physician-randomized quality improvement interventions CONTEMPORARY CLINICAL TRIALS Stedman, M. R., Gagnon, D. R., Lewa, R. A., Solomon, D. H., Brookhart, M. A. 2008; 29 (5): 687-695

  Abstract

  Health care quality improvement interventions are often evaluated in randomized trials in which individual physicians serve as the unit of randomization. These cluster randomized trials present a unique data structure that consists of many clusters of highly variable size. The appropriate method of analysis for these trials is unknown. We conducted a simulation study to compare several methods for analyzing data which were generated to replicate the structure of our motivating example. We varied the treatment effect size and the distributional assumptions about the random effect. Simulation was used to estimate power, coverage, bias, and mean squared error of full maximum likelihood estimation (MLE), approximate MLE using penalized quasi-likelihood (PQL), generalized estimating equations (GEE), group-bootstrapped logistic regression, and a clustered permutation test. Across all conditions tested, GEE and full MLE performed comparably. Bootstrapped methods were less powerful and had higher mean squared error under conditions of variable cluster size. PQL yielded biased results. The permutation test preserved Type I error rates, but had less power than the other methods considered.

  View details for DOI 10.1016/j.cct.2008.04.003

  View details for Web of Science ID 000259424400008

  View details for PubMedID 18571476

• Medical comorbidity and health-related quality of life in bipolar disorder across the adult age span JOURNAL OF AFFECTIVE DISORDERS Fenn, H. H., Bauer, M. S., Alshuler, L., Evans, D. R., Williford, W. O., Kilbourne, A. M., Beresford, T. P., Kirk, G., Stedman, M., Fiore, L. 2005; 86 (1): 47-60

  Abstract

  Little is known about medical comorbidity or health-related quality of life (HRQOL) in bipolar disorder across the adult age span, especially in public sector patients.We obtained cross-sectional demographic, clinical, and functional ratings for 330 veterans hospitalized for bipolar disorder with Mini-Mental State score > or = 27 and without active alcohol/substance intoxication or withdrawal, who had had at least 2 prior psychiatric admissions in the last 5 years. Structured medical record review identified current/lifetime comorbid medical conditions. SF-36 Physical (PCS) and Mental (MCS) Component Scores, measured physical and mental HRQOL. Univariate and multivariate analyses addressed main hypotheses that physical and mental function decrease with age with decrements due to increasing medical comorbidity.PCS decreased (worsened) with age; number of current comorbid medical diagnoses, but not age, explained the decline. Older individuals had higher (better) MCS, even without controlling for medical comorbidity. Multivariate analysis indicated association of MCS with age, current depressed/mixed episode, number of past-year depressive episodes, and current anxiety disorder, but not with medical comorbidity, number of past-year manic episodes, current substance disorder or lifetime comorbidities.This cross-sectional design studied a predominantly male hospitalized sample who qualified for and consented to subsequent randomized treatment.Medical comorbidity is associated with lower (worse) physical HRQOL, independent of age. Surprisingly, younger rather than older subjects reported lower mental HRQOL. This appears due in part to more complex psychiatric presentations, and several mechanisms are discussed. Both results suggest that age-specific assessment and treatment may enhance HRQOL outcome.

  View details for DOI 10.1016/j.jad.2004.12.006

  View details for Web of Science ID 000228632700006

  View details for PubMedID 15820270