Petterson, Tanya M.

Background. Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality. Methods. We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality. Results. Of the 2183 patients evaluated, 59.1% were male, 81.4% were white, and 11.4% died during follow-up. Mean ECG age was 59.0 ± 12.0 y and mean chronological age at ECG was 53.3 ± 13.6 y. After adjusting for chronological age, comorbidities, and other characteristics associated with mortality, each increase in ECG age of >10 y than the average ECG age for patients of a similar chronological age was associated with an increase in mortality risk (hazard ratio 3.59 per 10-y increase; 95% confidence interval, 2.06-5.72; P < 0.0001). Conclusions. ECG age is a risk factor for KT waitlist mortality. Determining ECG age through artificial intelligence may help guide risk-benefit assessment when evaluating candidates for KT.

Background. Limited health literacy (HL) is associated with decreased kidney function and death in patients with chronic kidney disease. Less is known about the impact of HL on kidney transplant (KT) outcomes. The aim of this study was to examine the relationship between HL and KT outcomes, including rates of waitlisting, healthcare utilization, acute rejection, renal allograft function, renal allograft failure, and death. Methods. We performed a retrospective review of HL data previously collected at our center. HL was assessed in a convenience sample of consecutive, English-speaking patients age ≥18 y who were evaluated for KT at Mayo Clinic in Minnesota between June 2015 and March 2017 as part of a practice improvement feasibility project (n = 690). HL was assessed using the 4-item Brief Health Literacy Screening Tool modified for the outpatient KT evaluation process. The 4 items assess confidence completing forms, reading comprehension, and oral literacy. Results. Overall, 30.4% of patients had limited or marginal HL. Patients with limited or marginal HL were less likely than those with adequate HL to be waitlisted for KT (hazard ratio = 0.62 and 0.69, respectively), even after adjusting for age, marital status, body mass index, Charlson comorbidity index, or dialysis dependency. Patient HL was not associated with post-KT healthcare utilization, acute rejection, or renal allograft function. Patients with limited or marginal HL appeared to experience a higher risk of renal allograft failure and post-KT death, but the number of events was small, and the relationship was statistically significant only for marginal HL. Conclusions. Inadequate HL is common in KT candidates and independently associated with decreased waitlisting for KT. We observed no statistically significant relationship between HL and posttransplant outcomes in our cohort. Further efforts to improve communication in patients with inadequate HL may improve access to KT.

Abstract Background Treatment burden refers to the work involved in managing one’s health and its impact on well-being and has been associated with nonadherence in patients with chronic illnesses. No kidney transplant (KT)-specific measure of treatment burden exists. The aim of this study was to develop a KT-specific supplement to the Patient Experience with Treatment and Self-Management (PETS), a general measure of treatment burden. Methods After drafting and pretesting KT-specific survey items, we conducted a cross-sectional survey study involving KT recipients from Mayo Clinic in Minnesota, Arizona, and Florida. Exploratory factor analysis (EFA) was used to identify domains for scaling the KT-specific supplement. Construct and known-groups validity were determined. Results Survey respondents (n = 167) had a mean age of 61 years (range 22–86) and received a KT on average 4.0 years ago. Three KT-specific scales were identified (transplant function, self-management, adverse effects). Higher scores on the KT-specific scales were correlated with higher PETS treatment burden, worse physical and mental health, and lower self-efficacy (p < 0.0001). Patients taking more medications reported higher transplant self-management burden. Conclusions We developed a KT-specific supplement to the PETS general measure of treatment burden. Scores may help providers identify recipients at risk for nonadherence.

Background: Whether VTE risk can be further stratified among patients with neurologic disease and leg paresis is unknown. Objective: To identify independent risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE) among patients with neurologic disease and leg paresis. Methods: Using the population-based resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with incident DVT or PE over the 45-year period, 1966 to 2010. We performed a case-control study nested within the Olmsted County population with incident VTE associated with neurologic disease and leg paresis over the 18-year period, 1988-2010 (n=192). For each VTE case, we identified 1 Olmsted County resident with neurologic disease, leg paresis and no VTE (control) matched to each case on sex, date of birth (+/- 5 years), calendar year (+/- 1 year) and duration of medical records. Using conditional logistic regression, we tested duration of paresis (index-3 months, 3-12 months, and > 12 months), paresis etiology, and degree of immobility as potential risk factors for VTE after adjusting for other known VTE risk factors, including hospitalization for major surgery or acute medical illness, trauma/fracture, and active cancer. Results: In univariate analyses of the 192 pairs, trauma/fracture, hospitalization for major surgery or for acute medical illness, active cancer, duration of paresis, and degree of immobility were associated with VTE. In the multivariable analysis, hospitalization for acute medical illness, active cancer, degree of immobility (ambulatory without/with assistance, function from a wheelchair base, bed bound; OR: 2.60; 95%Cl: 1.65-4.11); p=<0.0001) were independent predictors of VTE. Conclusion: Among patients with neurologic disease and leg paresis, VTE risk can be further stratified by hospitalization for acute medical illness, active cancer and degree of immobility; these patients should be considered for VTE prophylaxis.

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein–Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8–26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04–0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03–0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.

Menopausal hormone treatments (MHT) may limit progression of CIMT, a measure of atherosclerosis, but pose a risk for ischemic stroke. To test candidate gene variation for an association with CIMT, DNA from 714 women participating in KEEPS, a clinical trial of MHT to prevent progression of atherosclerosis, was genotyped using custom Illumina Infinium iSelect chemistry. Single nucleotide polymorphisms (SNPs; 13,229) were genotyped within 769 genes within the anticoagulant, procoagulant, fibrinolytic or innate immunity pathways. Of these SNPs, 75 were removed due to call rate<0.95, relatedness, duplication, and misidentification; 1275 were removed for quality control. There were 504 ancestry informative markers (AIM). Percent of European ancestry using AIM, age at enrollment and pulse pressure correlated positively with CIMT. Using logistic regression to adjust for these, one SNP (rs2236935 of MAP4K4 on chromosome 2) associated positively with CIMT (p‐value = 5.771e‐06). This gene encodes a protein of the serine/threonine protein kinase family involved in cytokine signaling pathways related to innate immunity, development of type II diabetes, and response to environmental stress. Whether this SNP remains associated with changes in CIMT in women randomized to hormonal treatment in KEEPS remains to be determined. (Supported by grants from the Aurora Foundation, NIH HL90639 and the Mayo Foundation)

Objective: To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs). Methods: This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions. Results: 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4–6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89–2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17–1.54) after adjusting for all 16 comorbid chronic conditions. Conclusion: These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses.

Background: Parenthood during medical training is common and impacts trainee well-being. However, current graduate medical education parental health policies are often limited in scope. We explored current fellowship trainees’ knowledge of/satisfaction with current policies as well as interest in potential changes/additions to existing policies. Methods: Fellowship program directors/coordinators at a three-site academic institution were surveyed and information was collected from 2015 to 2019 regarding fellow demographics and parental health policies. We distributed an electronic survey to fellows containing Likert-type-scale questions rating knowledge/level of satisfaction with current parental health policies and interest in potential additions/modifications to current policies. Results: Thirty-five of 47 (74%) fellowship programs responded. An average of 11% of female fellows and 15% of male fellows took parental leave during the study period. Three (9%) of the programs had at least one additional parental health policy beyond institutional graduate medical education policies. In the fellow survey, 175 of 609 fellows responded (28.7%), of which 84 (48.6%) were female. Although 89.1% agreed/strongly agreed that parental health is an important part of health and well-being for fellows, only 32% were satisfied/very satisfied with current policies (no significant sex-related differences). Fellows reported the following potential interventions as important/very important: 79.2% increased (paid) maternity leave (72.7% male, 86.7% female, p = 0.02), 78% increased (paid) paternity leave (76.4% male, 81.9% female, p = 0.37), 72.3% part-time return to work (60.2% male, 84.3% female, p = 0.0005), 63% coverage for workup/management of infertility (52.3% male, 74.7% female, p = 0.002), and 79.9% on-site day care (70.7% male, 89.2% female, p = 0.003). Conclusions: Parental health includes multiple domains, not all of which are covered by current policies. Fellows feel that parental health is an important part of overall health and well-being, but most are not satisfied with current policies. Expanded access to parental leave and new policies (part-time return to work, infertility management, and on-site day care) are opportunities for innovation.

Abstract Background: Active cancer is an independent predictor of recurrent venous thromboembolism (VTE; hazard ratio=2.2–4.2). However, whether the risk of VTE recurrence among active cancer patients can be further stratified by tumor site or presence of metastases is uncertain. Objectives: To estimate and compare the cumulative incidence of VTE recurrence by tumor site and presence of metastases among active cancer patients with incident VTE. Study Design and Population: Retrospective cohort study of Olmsted County, MN residents with active cancer who lived &gt;1 day after a first-lifetime deep vein thrombosis or pulmonary embolism over the 35-year period, 1966–2000 (n=418). 25 patients with oral (6), bone (1), skin (4), soft tissue (3), eye (1) and other/unknown (10) were excluded, leaving 393 remaining patients. Measurements: Baseline demographic and clinical characteristics, tumor site, presence and location of tumor metastases, and date of first recurrent VTE. Tumor site and metastases were tested as potential predictors of time-to-recurrent VTE using the Cox proportional hazards model. Results: 114 of 393 patients with active cancer developed recurrent VTE over 764 person-years of follow-up. The cumulative incidence of recurrent VTE at seven, 30, 90, and 180 days, 1, 5, and 10 years was 1.9%, 10.3%, 18.3%, 22.3%, 28.7%, 44.5%, and 53.5%, respectively. After adjusting for age and gender, tumor site was an independent predictor of first VTE recurrence (p&lt;0.01). The hazard of VTE recurrence was over 2-fold higher for lung cancer patients compared to the lowest recurrence group (kidney, bladder and other genitourinary cancer; HR=2.04, 95% CI: 0.88, 4.70, p=0.096), and the hazard for brain and pancreatic cancer was nearly 2-fold higher (HR=1.9 for each, p=0.22, 0.24, respectively). The hazard of recurrence among hematological; breast and ovarian; gastric, colon, and liver; and prostate cancer patients did not differ significantly from the lowest recurrence group. Univariately, the presence of metastases at cancer diagnosis was not associated with recurrent VTE (HR=1.16; 95% CI: 0.79, 1.69, p=0.45). Conclusions: Tumor site is an independent predictor of VTE recurrence after adjusting for age and gender. In particular, lung, brain and pancreatic cancer patients have the highest risk for recurrence and these patients should be considered for secondary prophylaxis. Disease severity, as reflected by metastatic disease at cancer diagnosis, is not a predictor of recurrence.