"What do you think about nephrology?" A national survey of internal medicine residents.

BACKGROUND: Interest in nephrology has been declining among internal medicine residents but the reasons behind this observation are not well characterized. Our objective was to evaluate factors influencing residents' choice of subspecialty. METHODS: This is a mixed-method QUAL-QUAN design study that used the results of our previously published qualitative analysis on residents' perception of nephrology to create and pilot a questionnaire of 60 questions. The final questionnaire was distributed to 26 programs across the United States and a total of 1992 residents. We calculated response rates and tabulated participant characteristics and percentage of participant responses. We categorized choice of fellowship into 2 medical categories (Highly Sought After vs. Less Sought After) and fitted a logistic regression model of choosing a highly vs. less sought after fellowship. RESULTS: Four hundred fifteen out of 1992 (21%) US residents responded to the survey. Of the 268 residents planning to pursue fellowship training, 67 (25%) selected a less sought after fellowship. Female sex was associated with significantly higher odds of selecting a less sought after fellowship (OR = 2.64, 95% CI: 1.47, 4.74). Major factors deterring residents from pursuing nephrology were perception of inadequate financial compensation, broad scope of clinical practice and complexity of patient population. We observed a decline in exposure to nephrology during the clinical years of medical school with only 35.4% of respondents rotating in nephrology versus 76.8% in residency. The quality of nephrology education was rated less positively during clinical medical school years (median of 50 on a 0-100 point scale) compared to the pre-clinical years (median 60) and residency (median 75). CONCLUSION: Our study attempts to explain the declining interest in nephrology. Results suggest potential targets for improvement: diversified trainee exposure, sub-specialization of nephrology, and increased involvement of nephrologists in the education of trainees.

Characteristics and Outcomes of Patients With Aortic Stenosis and Chronic Kidney Disease.

Background We sought to study longer term survival in patients with aortic stenosis ( AS ) and nondialysis chronic kidney disease ( CKD ). Methods and Results We studied 839 patients (aged 78±9 years and 51% male) with CKD and AS on echocardiogram from 2005 to 2012. Longer term all-cause and cardiovascular mortality was compared with a CKD group without AS , propensity matched for age, sex, race, left ventricular ejection fraction and CKD stage. Cox models were used to evaluate all-cause mortality and competing-risks regression models censored at time of aortic valve replacement to evaluate cardiac mortality in patients with AS and CKD . Overall, 511 (61%), 252 (30%), and 76 (9%) patients had CKD stages 3a, 3b, and 4, respectively; 93% had hypertension, 28% had diabetes mellitus, and 37% had coronary artery disease. In total, 185 (22%) had mild AS, 355 (42%) had moderate AS, and 299 (36%) had severe AS (66 symptomatic). Patients with CKD and AS had higher cardiac and all-cause mortality compared with controls with CKD and no AS ( P<0.001). Among patients with AS and CKD , there were 156 (19%) aortic valve replacements and 454 (54%) deaths (203 cardiac deaths) at 4.0±2.3 years of follow-up. Lower estimated glomerular filtration rate (hazard ratio per 10 mL/min per 1.73 m2: 1.18; 95% CI, 1.08-1.29) was associated with increased risk of all-cause mortality but not cardiac mortality (hazard ratio: 1.12; 95% CI, 0.97-1.30; P=0.13). Of patients undergoing aortic valve replacement, 61% had improvement in estimated glomerular filtration rate within 1 year (median percentage change=+2.8% per month). Conclusions Among patients with nondialysis CKD , AS is associated with significantly higher cardiac and all-cause mortality; lower estimated glomerular filtration rate is associated with increased mortality, and aortic valve replacement was associated with improved survival.

What are the Risk Factors for One-Year Mortality in Older Patients with Chronic Kidney Disease? An Analysis of the Cleveland Clinic CKD Registry.

BACKGROUND: Prognostic factors after dialysis initiation among older chronic kidney disease (CKD) patients are not well studied. In this study, we examined the risk factors associated with 1-year mortality after dialysis initiation among older CKD patients. METHODS: In this retrospective study, we included 621 CKD patients from an electronic medical record based CKD registry that was linked to the United States Renal Data System data. In terms of age, they were all ≥65. We examined the associations of various demographic factors, comorbid conditions, relevant laboratory parameters, the presence of arteriovenous fistula, and inability to take care of oneself with 1-year mortality after dialysis initiation using Cox proportional hazards model. RESULTS: In our study cohort, 224 older patients died during the first year of dialysis initiation and the estimated survival at 1 year was 65% (95% CI 62-69). After adjusting for covariates, increasing age by each year (Hazard ratio 1.04 [95% CI 1.02-1.06]), congestive heart failure (CHF; 1.57 [1.13-2.18]), an absence of AVF (3.0 [1.7-5.1]) and lack of nephrology care prior to dialysis initiation (1.93 [1.39-2.70]) were associated with increased risk of 1-year mortality. Nearly 60% of deaths were due to non-cardiovascular (CV) causes including cancer. CONCLUSION: Risk factors portending high 1-year mortality in older CKD patients are increasing age, CHF, an absence of AVF, and lack of pre-dialysis nephrology care. Clinicians need to be aware of non-CV risks of high mortality in these patients.

Intra-Arterial versus Intravenous Contrast and Renal Injury in Chronic Kidney Disease: A Propensity-Matched Analysis.

BACKGROUND/AIMS: contrast-induced nephropathy (CIN) is well described following an administration of intraarterial contrast, but its occurrence after intravenous (IV) contrast is being questioned. We evaluated the incidence of acute kidney injury (AKI), post-contrast AKI (PC-AKI), CIN, dialysis and mortality in patients with chronic kidney disease (CKD) undergoing non-contrast computed tomography (NCCT) or contrast CT (CCT) or coronary angiography (CoA). METHODS: We identified individuals who had CoA or CCT or NCCT between 2010 and 2015 in the Cleveland Clinic CKD registry. We used propensity scores to match patients in the 3 groups. We evaluated the proportion of patients that developed AKI and CIN across the groups with chi-square tests. We generated Kaplan-Meier plots comparing mortality and ESRD among patients who developed AKI (in the NCCT group), PC (multifactorial AKI, CIN) AKI and no AKI. RESULTS: Out of 251 eligible patients, 200 who had CoA were matched to each of the other CT scan groups. The incidence of AKI was 27% in CoA, 24% in CCT and 24% in NCCT (p = 0.72). The incidence of CIN AKI was 16.5% in CoA and 12.5% in CCT (p = 0.26). The Kaplan-Meier survival at 2 years was 74.8 (95% CI 63.8-87.7) for those with CIN and 53.2 (95% CI 39.7-71.4) for those with multifactorial AKI and 56.5 (95% CI 43.4-73.6) for those with AKI-NCCT and 71.4 (95% CI 67.2-76.0) for those without AKI. The Kaplan-Meier ESRD-free estimates at 2 years were 89.9 (95% CI 80.8-100) for those with CIN and 89.4 (95% CI 78.7-100) for those with multifactorial AKI and 77.4 (95% CI 63.6-94.3) for those with AKI-NCCT and 94.4 (95% CI 91.9-97.1) for those without AKI. CONCLUSION: The administration of both IV and intra-arterial contrast is associated with a risk of AKI. Multifactorial AKI was associated with worse outcomes, while CIN was associated with better outcomes.

Phosphorus binders: The new and the old, and how to choose.

In caring for patients with chronic kidney disease, it is important to prevent and treat hyperphosphatemia with a combination of dietary restrictions and phosphorus binders. This review describes the pathophysiology and control of hyperphosphatemia and the different classes of phosphorus binders with respect to their availability, cost, side effects, and scenarios in which one class of binder may be more beneficial than another.

Cause-Specific Mortality in Patients with Chronic Kidney Disease and Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with death in patients with chronic kidney disease (CKD). We examined the associations between AF and cause-specific mortality in a large CKD population. METHODS: We included 62,459 patients with estimated glomerular filtration rate 15-59 mL/min/1.73 m2 (6,639 patients with AF and 55,820 without AF) followed in a large health care system. Outcomes included overall and cause-specific deaths (a) cardiovascular; (b) malignancy; and (c) non-cardiovascular/non-malignancy causes. Cox regression models for overall mortality and separate competing risk models for each major cause of death category were used to evaluate their respective associations with AF. RESULTS: During a median follow-up of 4.1 years, 19,094 patients died; cause of death was known for 18,854 patients. After multivariable adjustment (demographics, comorbidities, relevant laboratory data, medication use, and kidney function), AF was associated with 23% (95% CI 18-29%) higher risk of all-cause mortality, 45% (95% CI 31-61%) higher risk of cardiovascular mortality and 13% (95% CI 3-22%) lower risk of malignancy-related mortality. Exclusion of patients with malignancy yielded similar results except for a lack of association between AF and malignancy-related deaths. Results were consistent across various stages of CKD. CONCLUSIONS: In a non-dialysis-dependent CKD population, the presence of AF was associated with higher all-cause and cardiovascular mortality. These data suggest that patients with both CKD and AF are at high cardiovascular risk, and thus clinical practice (or trials) should aim at reducing the overall excess cardiovascular mortality (not stroke alone) in patients with AF and CKD.

High-density lipoprotein cholesterol and causes of death in chronic kidney disease.

BACKGROUND: Recent data suggest a U-shaped association between high-density lipoprotein cholesterol (HDL-c) and death in chronic kidney disease (CKD). However, whether the increased mortality in patients with extreme levels is explained by specific causes of death remains unclear. OBJECTIVES: We studied the associations between HDL-c and cause-specific deaths in CKD. METHODS: We included 38,377 patients with estimated glomerular filtration rate 15-59 mL/min/1.73 m2. We classified deaths into 3 major categories: (1) cardiovascular; (2) malignant; and (3) noncardiovascular/nonmalignant causes. We fitted Cox regression models for overall mortality and separate competing risk models for each major cause of death category to evaluate their respective associations with categories of HDL-c (≤30, 31-40, 41-50 [referent], 51-60, >60 mg/dL). Separate analyses were conducted for men and women. RESULTS: During a median follow-up of 4.5 years, 9665 patients died. After adjusting for relevant covariates, in both sexes, HDL-c 31 to 40 mg/dL and ≤30 mg/dL were associated with higher risk of all-cause mortality, cardiovascular mortality, malignancy-related deaths, and noncardiovascular/nonmalignancy-related deaths. HDL-c >60 mg/dL was associated with lower all-cause (hazard ratio: 0.75, 95% confidence interval: 0.69, 0.81), cardiovascular, malignancy-related, and noncardiovascular/nonmalignancy-related deaths among women but not in men. Similar results were noted when HDL-c was examined as a continuous measure. CONCLUSIONS: In a non-dialysis-dependent CKD population, HDL-c ≤40 mg/dL was associated with risk of higher all-cause, cardiovascular, malignant, and noncardiovascular/nonmalignant mortality in men and women. HDL >60 mg/dL was associated with lower risk of all-cause, cardiovascular, malignant, and noncardiovascular/nonmalignant mortality in women but not in men.

Chronic kidney disease in African Americans: Puzzle pieces are falling into place.

Recent decades have seen great advances in the understanding of chronic kidney disease, spurred by standardizing disease definitions and large-scale patient surveillance. African Americans are disproportionately affected by the disease, and recently discovered genetic variants in APOL1 that protect against sleeping sickness in Africa provide an important explanation for the increased burden. Studies are now under way to determine if genetic testing of African American transplant donors and recipients is advisable.

Impact of Uric Acid Levels on Kidney Disease Progression.

BACKGROUND: Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry. METHODS: We included 1,676 patients with CKD stages 3 and 4 from Ohio, who had measured their uric acid (UA) levels a year prior to the recording of the second eGFR <60 mL/min/1.73 m2, and follow-up eGFR, between 2005 and 2009. Our primary composite outcome included a 50% drop in eGFR or progression to ESRD. Secondary outcomes included the rate of decline in eGFR, all-cause mortality, progression to ESRD, and a composite measure of progression to ESRD or death. We assessed the association between UA, UALT, and outcomes using Cox models and competing risks regression models. RESULTS: In multivariable models, higher UA was associated with the composite endpoint, but it reached statistical significance only in the 4th quartile (≥8.9 mg/dL). Receipt of UALT was significantly associated with increased risk of the composite outcome. Neither UA nor UALT (considered a time-dependent covariate) was significantly associated with mortality. The inference was similar for UA as high vs. low, quartiles, or continuous. Similarly, neither high UA nor UALT were significantly associated with ESRD, the composite of ESRD and mortality, or eGFR decline. CONCLUSIONS: Hyperuricemia is associated with increased risk of progression to ESRD in patients with CKD stages 3 and 4, but UALT does not ameliorate the risk, suggesting that the relationship is not causal.

Pragmatic Randomized, Controlled Trial of Patient Navigators and Enhanced Personal Health Records in CKD.

BACKGROUND AND OBJECTIVES: Patient navigators and enhanced personal health records improve the quality of health care delivered in other disease states. We aimed to develop a navigator program for patients with CKD and an electronic health record-based enhanced personal health record to disseminate CKD stage-specific goals of care and education. We also conducted a pragmatic randomized clinical trial to compare the effect of a navigator program for patients with CKD with enhanced personal health record and compare their combination compared with usual care among patients with CKD stage 3b/4. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two hundred and nine patients from six outpatient clinics (in both primary care and nephrology settings) were randomized in a 2×2 factorial design into four-study groups: (1) enhanced personal health record only, (2) patient navigator only, (3) both, and (4) usual care (control) group. Primary outcome measure was the change in eGFR over a 2-year follow-up period. Secondary outcome measures included acquisition of appropriate CKD-related laboratory measures, specialty referrals, and hospitalization rates. RESULTS: Median age of the study population was 68 years old, and 75% were white. At study entry, 54% of patients were followed by nephrologists, and 88% were on renin-angiotensin system blockers. After a 2-year follow-up, rate of decline in eGFR was similar across the four groups (P=0.19). Measurements of CKD-related laboratory parameters were not significantly different among the groups. Furthermore, referral for dialysis education and vascular access placement, emergency room visits, and hospitalization rates were not statistically significant different between the groups. CONCLUSIONS: We successfully developed a patient navigator program and an enhanced personal health record for the CKD population. However, there were no differences in eGFR decline and other outcomes among the study groups. Larger and long-term studies along with cost-effectiveness analyses are needed to evaluate the role of patient navigators and patient education through an enhanced personal health record in those with CKD.

Blood pressure parameters are associated with all-cause and cause-specific mortality in chronic kidney disease.

Previous observational studies reported J or U-shaped associations between blood pressure parameters and mortality in patients with chronic kidney disease (CKD). Here we examined the associations of different blood pressure levels with various causes of death in a CKD population that included patients with eGFR 15-59 ml/min/1.73 m2 with underlying hypertension receiving at least one antihypertensive agent. We obtained data on date and cause of death from State Department of Health mortality files and classified deaths into three categories: cardiovascular, malignancy-related, and non-cardiovascular/non-malignancy related. Cox models were fitted for overall mortality, and separate competing risk regression models for each major cause of death category, to evaluate their associations with various systolic and diastolic blood pressures. During a median follow-up of 3.9 years, 13,332 of 45,412 patients died. Systolic blood pressures under 100, 100-109, 110-119, and over 150 (vs. 130-139 mm Hg) were associated with higher all-cause and cardiovascular mortality. Systolic blood pressures under 100 mm Hg and 100-109 were associated with higher non-cardiovascular/non-malignancy related mortality. Diastolic blood pressures under 50 and 50-59 (vs. 70-79 mm Hg) were associated with higher all-cause and non-cardiovascular/non-malignancy-related mortality while diastolic blood pressures over 90 mm Hg was associated with higher cardiovascular but lower non-cardiovascular/non-malignancy related mortality. Thus, in a non-dialysis dependent CKD population, systolic blood pressures under 110 and over 150 mm Hg were associated with cardiovascular and non-cardiovascular/non-malignancy related deaths. However, diastolic blood pressure under 60 mm Hg was associated in contrast with all-cause mortality and non-cardiovascular/non-malignancy-related deaths.

Diabetes Control and the Risks of ESRD and Mortality in Patients With CKD.

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD) and a significant contributor to mortality in the general population. We examined the associations of hemoglobin A1c (HbA1c) levels with ESRD and death in a population with diabetes and chronic kidney disease (CKD). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 6,165 patients with diabetes (treated with oral hypoglycemic agents and/or insulin) and CKD stages 1 to 5 at a large health care system. PREDICTOR: HbA1c level (examined as a categorical and continuous measure). OUTCOMES: All-cause and cause-specific mortality ascertained from the Ohio Department of Health mortality files and ESRD ascertained from the US Renal Data System. RESULTS: During a median 2.3 years of follow-up, 957 patients died (887 pre-ESRD deaths) and 205 patients reached ESRD. In a Cox proportional hazards model, after multivariable adjustment including for kidney function, HbA1c level < 6% was associated with higher risk for death when compared with HbA1c levels of 6% to 6.9% (HR, 1.23; 95% CI, 1.01-1.50). Similarly, HbA1c level ≥ 9% was associated with higher risk for all-cause death (HR, 1.34; 95% CI, 1.06-1.69). In competing-risk models, baseline HbA1c level was not associated with ESRD. For cause-specific mortality, diabetes accounted for >12% of deaths overall and >19% of deaths among those with HbA1c levels > 9%. LIMITATIONS: Small proportion of participants with advanced kidney disease; single-center population. CONCLUSIONS: In this cohort of patients with CKD with diabetes, HbA1c levels < 6% and ≥9% were associated with higher risk for death. HbA1c levels were not associated with ESRD in this specific CKD population. Diabetes-related deaths increased with higher HbA1c levels.

Associations of dysnatremias with mortality in chronic kidney disease.

BACKGROUND: Hyponatremia and hypernatremia are associated with death in the general population and those with chronic kidney disease (CKD). We studied the associations between dysnatremias, all-cause mortality and causes of death in a large cohort of Stage 3 and 4 CKD patients. METHODS: We included 45 333 patients with Stage 3 and 4 CKDs followed in a large healthcare system. Associations between hyponatremia (<136 mmol/L) and hypernatremia (>145), and all-cause mortality and causes of death (cardiovascular, malignancy related and non-cardiovascular/non-malignancy related) were studied using Cox proportional hazards and competing risk models. RESULTS: Dysnatremias were found in 9.2% of the study population. In separate multivariable Cox proportional hazards models using baseline serum sodium levels and time-dependent repeated measures, both hyponatremia and hypernatremia were associated with all-cause mortality. In the competing risk analyses, hyponatremia was significantly associated with increased risk for various cause-specific mortality categories [cardiovascular (hazard ratio, HR 1.16, 95% confidence interval, CI: 1.04, 1.30), malignancy related (HR 1.48, 95% CI: 1.33, 1.65) and non-cardiovascular/non-malignancy deaths (HR 1.25, 95% CI: 1.13, 1.39)], while hypernatremia was significantly associated with higher non-cardiovascular/non-malignancy mortality only (HR 1.36, 95% CI: 1.08, 1.72). CONCLUSIONS: In those with CKD, hyponatremia was associated with all-cause mortality, cardiovascular, malignancy and non-cardiovascular/non-malignancy-related deaths. Hypernatremia was associated with all-cause and non-cardiovascular/non-malignancy-related deaths. Further studies are needed to elucidate the mechanisms of differences in cause-specific death among CKD patients with hyponatremia and hypernatremia.

Outcomes of In-Hospital Cardiopulmonary Resuscitation in Patients with CKD.

BACKGROUND AND OBJECTIVES: Advance care planning, including code/resuscitation status discussion, is an essential part of the medical care of patients with CKD. There is little information on the outcomes of cardiopulmonary resuscitation in these patients. We aimed to measure cardiopulmonary resuscitation outcomes in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study is observational in nature. We compared the following cardiopulmonary resuscitation-related outcomes in patients with CKD with those in the general population by using the Nationwide Inpatient Sample (2005-2011): (1) survival to hospital discharge, (2) discharge destination, and (3) length of hospital stay. All of the patients were 18 years old or older. RESULTS: During the study period, 71,961 patients with CKD underwent in-hospital cardiopulmonary resuscitation compared with 323,620 patients from the general population. Unadjusted in-hospital mortality rates were higher in patients with CKD (75% versus 72%; P<0.001) on univariate analysis. After adjusting for age, sex, and potential confounders, patients with CKD had higher odds of mortality (odds ratio, 1.24; 95% confidence interval, 1.11 to 1.34; P≤0.001) and length of stay (odds ratio, 1.11; 95% confidence interval, 1.07 to 1.15; P=0.001). Hospitalization charges were also greater in patients with CKD. There was no overall difference in postcardiopulmonary resuscitation nursing home placement between the two groups. In a separate subanalysis of patients ≥75 years old with CKD, higher odds of in-hospital mortality were also seen in the patients with CKD (odds ratio, 1.10; 95% confidence interval, 1.02 to 1.17; P=0.01). CONCLUSIONS: In conclusion, we observed slightly higher in-hospital mortality in patients with CKD undergoing in-hospital cardiopulmonary resuscitation.

Interpreting SPRINT: How low should you go?

The Systolic Blood Pressure Intervention Trial (SPRINT) found evidence of cardiovascular benefit with intensive lowering of systolic blood pressure (goal < 120 mm Hg) compared with the currently recommended goal (< 140 mm Hg) in older patients with cardiovascular risk but without diabetes or stroke. This article reviews the trial design and protocol, summarizes the results, and briefly discusses the implications of these results.

Body mass index and causes of death in chronic kidney disease.

In chronic kidney disease (CKD), a higher body mass index (BMI) is associated with a lower risk for death, but cause-specific death details are unknown across the BMI range. To define this, we studied 54,506 patients with CKD (stage 3 CKD- [91.5%]) from an institutional electronic medical record based-registry. We examined the associations among various causes of death (cardiovascular-, malignancy- and noncardiovascular/nonmalignancy-related deaths) across the BMI range using Cox proportional hazards and competing risks regression models. During a median follow-up of 3.7 years, 14,518 patients died. In the multivariable model, an inverted J-shaped association was noted between BMI and cardiovascular-related, malignancy-related, and noncardiovascular/nonmalignancy-related deaths. Similar associations were noted for BMI 25-29.9, 30-34.9, and 35-39.9 kg/m(2) categories. A BMI >40 kg/m(2) was not associated with cardiovascular-related and noncardiovascular/nonmalignancy-related deaths in CKD. Sensitivity analyses yielded similar results even after adjusting for proteinuria and excluding diabetes and hypertension from the models. In CKD, compared with a BMI of 18.5-24.9 kg/m(2), those who are overweight, with class 1 and 2 obesity have a lower risk for cardiovascular-related, malignancy-related, and noncardiovascular/nonmalignancy-related deaths. Future studies should examine the associations of other measures of adiposity with outcomes in CKD.

Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with higher mortality in the general population. We studied the associations between COPD and death among chronic kidney disease (CKD) patients along with reporting cause-specific death data. METHODS: We included 56,960 patients with stages 3 and 4 CKD who were followed in a large health care system. Associations between COPD and all-cause mortality and various causes of death (respiratory deaths, cardiovascular deaths, malignancy-related deaths and deaths due to other reasons) were studied using the Cox proportional hazards and competing risk models. RESULTS: Out of 56,960 CKD patients, 4.7% (n = 2,667) had underlying COPD. Old age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, and smoking were associated with higher risk for COPD. During a median follow-up of 3.7 years, 15,969 patients died. After covariate adjustment, COPD was associated with a 41% increased risk (95% CI 1.31-1.52) for all-cause mortality, and fourfold increased risk (sub-hazard ratio 4.36, 95% CI 3.54-5.37) for respiratory-related deaths. In a sensitivity analysis that was performed by defining COPD as the use of relevant International Classification of Diseases-9 codes and medications used to treat COPD, similar results were noted. CONCLUSIONS: COPD is associated with higher risk for death among those with CKD, and an underlying lung disease accounts for significant proportion of deaths. These data highlight the need for further prospective studies to understand the underlying mechanisms and potential interventions to improve outcomes in this population.