Faculty Bibliography

Epidemiology should aim to improve population health; however, no consensus exists regarding the activities and skills that should be prioritized to achieve this goal. We performed a scoping review of articles addressing the translation of epidemiologic knowledge into improved population health outcomes. We identified 5 themes in the translational epidemiology literature: foundations of epidemiologic thinking, evidence-based public health or medicine, epidemiologic education, implementation science, and community-engaged research (including literature on community-based participatory research). We then identified 5 priority areas for advancing translational epidemiology: 1) scientific engagement with public health; 2) public health communication; 3) epidemiologic education; 4) epidemiology and implementation; and 5) community involvement. Using these priority areas as a starting point, we developed a conceptual framework of translational epidemiology that emphasizes interconnectedness and feedback among epidemiology, foundational science, and public health stakeholders. We also identified 2-5 representative principles in each priority area that could serve as the basis for advancing a vision of translational epidemiology. We believe an emphasis on translational epidemiology can help the broader field to increase the efficiency of translating epidemiologic knowledge into improved health outcomes and to achieve its goal of improving population health.

Importance:Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. Objective:To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. Design, Setting, and Participants:A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. Exposures:At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). Main Outcomes and Measures:The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Results:Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P = .57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P = .04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P = .06; P = .75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P < .001; P = .047 for interaction). Conclusions and Relevance:This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status.

Impacts of the prescription opioid epidemic have not yet been examined in the context of heart transplantation. We examined a novel database in which national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2016) to characterize prescription opioid use before and after heart transplant, and associations (adjusted hazard ratio, _{95% LCL} aHR_{95% UCL} ) with death and graft loss. Among 13 958 eligible patients, 40% filled opioids in the year before transplant. Use was more common among recipients who were female, white, or unemployed, or who underwent transplant in more recent years. Of those with the highest level of pretransplant opioid use, 71% continued opioid use posttransplant. Pretransplant use had graded associations with 1-year posttransplant outcomes; compared with no use, the highest-level use (>1000 mg morphine equivalents) predicted 33% increased risk of death (aHR _1.10 1.33_1.61 ) in the year after transplant. Risk relationships with opioid use in the first year posttransplant were stronger, with highest level use predicting 70% higher mortality (aHR _1.46 1.70_1.98 ) over the subsequent 4 years (from >1 to 5 years posttransplant). While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.

BACKGROUND:Recipients of nonkidney solid organ transplants (nkSOT) are living longer, and 11%-18% will develop end stage renal disease (ESRD). While our general inclination is to treat nkSOT recipients who develop ESRD with a kidney transplant (KT), an increasing number are developing ESRD at an older age where KT may not be the most appropriate treatment. It is possible that the risk of older age and prior nkSOT might synergize to make KT too risky, but this has never been explored. METHODS:To examine death-censored graft loss and mortality for KT recipients with and without prior nkSOT, we used Scientific Registry of Transplant Recipients data to identify 42 089 older (age ≥65) KT recipients between 1995 and 2016. Additionally, to better understand treatment options for these patients and survival benefit of KT, we identified 5023 older (age ≥65) with prior nkSOT recipients listed for subsequent KT, of whom 863 received transplants. RESULTS:Compared with 41 159 older KT recipients without prior nkSOT, death-censored graft loss was similar (adjusted hazard ratio [aHR]: 1.13, 95% CI: 0.93-1.37, P = 0.2), but mortality (aHR: 1.40, 95% CI: 1.28-1.54, P < 0.001) was greater for older KT recipients with prior nkSOT. Nonetheless, in a survival benefit model (survival with versus without the transplant), among older prior nkSOT recipients, KT decreased the risk of mortality by more than half (aHR: 0.47, 95% CI: 0.42-0.54, P < 0.001). CONCLUSIONS:Older prior nkSOT recipients who subsequently develop ESRD derive survival benefit from KT, but graft longevity is limited by overall survival in this population. These findings can help guide patient counseling for this challenging population.

Pediatric kidney transplant candidates often have multiple potential living donors (LDs); no evidence-based tool exists to compare potential LDs, or to decide between marginal LDs and deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P-LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all-cause graft loss as a function of living donor characteristics and DD KDPI. HLA-B mismatch (adjusted hazard ratio [aHR] per mismatch = _1.04 1.27_1.55 ), HLA-DR mismatch (aHR per mismatch = _1.02 1.23_1.49 ), ABO incompatibility (aHR = _1.20 3.26_8.81 ), donor systolic blood pressure (aHR per 10 mm Hg = _1.01 1.07_1.18 ), and donor estimated GFR (eGFR; aHR per 10 mL/min/1.73 m² = _0.88 0.94_0.99 ) were associated with graft loss after LDKT. Median (interquartile range [IQR]) P-LKDPI was -25 (-56 to 12). 68% of donors had P-LKDPI <0 (less risk than any DD kidney) and 25% of donors had P-LKDPI >14 (more risk than median DD kidney among pediatric KT recipients during the study period). Strata of LDKT recipients of kidneys with higher P-LKDPI had a higher cumulative incidence of graft loss (39% at 10 years for P-LDKPI ≥20, 28% for 20> P-LKDPI ≥-20, 23% for -20 > P-LKDPI ≥-60, 19% for P-LKDPI <-60 [log rank P < .001]). The P-LKDPI can aid in organ selection for pediatric KT recipients by allowing comparison of potential LD and DD kidneys.

RATIONALE & OBJECTIVE:There is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT). STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:Using national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT. EXPOSURES:Relative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain. OUTCOMES:We examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality. ANALYTIC APPROACH:Unadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models. RESULTS:Among 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality. LIMITATIONS:Unmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error. CONCLUSIONS:DDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

OBJECTIVES:Older adults who undergo kidney transplantation (KT) are living longer with a functioning graft and are at risk for age-related adverse events including fractures. Understanding recipient, transplant, and donor factors and the outcomes associated with fractures may help identify older KT recipients at increased risk. We determined incidence of hip, vertebral, and extremity fractures; assessed factors associated with incident fractures; and estimated associations between fractures and subsequent death-censored graft loss (DCGL) and mortality. DESIGN:This was a prospective cohort study of patients who underwent their first KT between January 1, 1999, and December 31, 2014. SETTING:We linked data from the Scientific Registry of Transplant Recipients to Medicare claims through the US Renal Data System. PARTICIPANTS:The analytic population included 47 815 KT recipients aged 55 years or older. MEASUREMENTS:We assessed the cumulative incidence of and factors associated with post-KT fractures (hip, vertebral, or extremity) using competing risks models. We estimated risk of DCGL and mortality after fracture using adjusted Cox proportional hazards models. RESULTS:The 5-year incidence of post-KT hip, vertebral, and extremity fracture for those aged 65 to 69 years was 2.2%, 1.0%, and 1.7%, respectively. Increasing age was associated with higher hip (adjusted hazard ratio [aHR] = 1.37 per 5-y increase; 95% confidence interval [CI] = 1.30-1.45) and vertebral (aHR = 1.31; 95% CI = 1.20-1.42) but not extremity (aHR = .97; 95% CI = .91-1.04) fracture risk. DCGL risk was higher after hip (aHR = 1.34; 95% CI = 1.12-1.60) and extremity (aHR = 1.30; 95% CI = 1.08-1.57) fracture. Mortality risk was higher after hip (aHR = 2.31; 95% CI = 2.11-2.52), vertebral (aHR = 2.80; 95% CI = 2.44-3.21), and extremity (aHR = 1.85; 95% CI = 1.64-2.10) fracture. CONCLUSION:Our findings suggest that older KT recipients are at higher risk for hip and vertebral fracture but not extremity fracture; and those with hip, vertebral, or extremity fracture are more likely to experience subsequent graft loss or mortality. These findings underscore that different fracture types may have different underlying etiologies and risks, and they should be approached accordingly. J Am Geriatr Soc 67:1680-1688, 2019.