Arteriovenous Vascular Access-Related Procedural Burden Among Incident Hemodialysis Patients in the United States.

RATIONALE & OBJECTIVE: As the proportion of arteriovenous fistulas (AVFs) compared with arteriovenous grafts (AVGs) in the United States has increased, there has been a concurrent increase in interventions. We explored AVF and AVG maturation and maintenance procedural burden in the first year of hemodialysis. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Patients initiating hemodialysis from July 1, 2012, to December 31, 2014, and having a first-time AVF or AVG placement between dialysis initiation and 1 year (N = 73,027), identified using the US Renal Data System (USRDS). PREDICTORS: Patient characteristics. OUTCOME: Successful AVF/AVG use and intervention procedure burden. ANALYTICAL APPROACH: For each group, we analyzed interventional procedure rates during maturation maintenance phases using Poisson regression. We used proportional rate modeling for covariate-adjusted analysis of interventional procedure rates during the maintenance phase. RESULTS: During the maturation phase, 13,989 of 57,275 patients (24.4%) in the AVF group required intervention, with therapeutic interventional requirements of 0.36 per person. In the AVG group 2,904 of 15,572 patients (18.4%) required intervention during maturation, with therapeutic interventional requirements of 0.28 per person. During the maintenance phase, in the AVF group 12,732 of 32,115 patients (39.6%) required intervention, with a therapeutic intervention rate of 0.93 per person-year. During maintenance phase, in the AVG group 5,928 of 10,271 patients (57.7%) required intervention, with a therapeutic intervention rate of 1.87 per person-year. For both phases, the intervention rates for AVF tended to be higher on the East Coast while those for AVG were more uniform geographically. LIMITATIONS: This study relies on administrative data, with monthly recording of access use. CONCLUSIONS: During maturation, interventions for both AVFs and AVGs were relatively common. Once successfully matured, AVFs had lower maintenance interventional requirements. During the maturation and maintenance phases, there were geographic variations in AVF intervention rates that warrant additional study.

Does One Size Fit All With the Effects of Payment Reform? Dialysis Facility Payer Mix and Anemia Management Under the Expanded Medicare Prospective Payment System.

BACKGROUND: The effects of Medicare payment reforms aiming to improve the efficiency and quality of care by establishing greater financial accountability for providers may vary based on the extent and types of other coverage for their patient populations. Providers who are more resource constrained due to a less favorable payer mix face greater financial risks under such reforms. The impact of the expanded Medicare dialysis prospective payment system (PPS) on quality of care in independent dialysis facilities may vary based on the extent of higher payments from private insurers available for managing increased risks. OBJECTIVES: To evaluate whether anemia outcomes for dialysis patients in independent facilities differ under the Medicare PPS based on facility payer mix. DESIGN: We examined changes in anemia outcomes for 122,641 Medicare dialysis patients in 921 independent facilities during 2009-2014 among facilities with differing levels of employer insurance (EI). We performed similar analyses of facilities affiliated with large dialysis organizations, whose practices were not expected to change based on facility-specific payer mix. RESULTS: Among independent facilities, similar modeled trends in low hemoglobin for all 3 facility EI groups in 2009-2010 were followed by increased low hemoglobin during 2012-2014 for facilities with lower EI (P<0.01). Post-PPS standardized blood transfusion ratios were 9% higher for lower EI versus higher EI independent facilities (P<0.01). Among large dialysis organizations facilities, there was no divergence in low hemoglobin by payer mix under the PPS. CONCLUSIONS: There is evidence of poorer quality of care for anemia under the PPS in independent facilities with lower versus higher EI. Provider responses to payment reform may vary based on attributes such as payer mix that could have implications for health disparities.

Computationally efficient inference for center effects based on restricted mean survival time.

Restricted mean survival time (RMST) has gained increased attention in biostatistical and clinical studies. Directly modeling RMST (as opposed to modeling then transforming the hazard function) is appealing computationally and in terms of interpreting covariate effects. We propose computationally convenient methods for evaluating center effects based on RMST. A multiplicative model for the RMST is assumed. Estimation proceeds through an algorithm analogous to stratification, which permits the evaluation of thousands of centers. We derive the asymptotic properties of the proposed estimators and evaluate finite sample performance through simulation. We demonstrate that considerable decreases in computational burden are achievable through the proposed methods, in terms of both storage requirements and run time. The methods are applied to evaluate more than 5000 US dialysis facilities using data from a national end-stage renal disease registry.

Arteriovenous Fistula Maturation in Prevalent Hemodialysis Patients in the United States: A National Study.

BACKGROUND: Arteriovenous fistulas (AVFs) are the preferred form of hemodialysis vascular access, but maturation failures occur frequently, often resulting in prolonged catheter use. We sought to characterize AVF maturation in a national sample of prevalent hemodialysis patients in the United States. STUDY DESIGN: Nonconcurrent observational cohort study. SETTING & PARTICIPANTS: Prevalent hemodialysis patients having had at least 1 new AVF placed during 2013, as identified using Medicare claims data in the US Renal Data System. PREDICTORS: Demographics, geographic location, dialysis vintage, comorbid conditions. OUTCOMES: Successful maturation following placement defined by subsequent use identified using monthly CROWNWeb data. MEASUREMENTS: AVF maturation rates were compared across strata of predictors. Patients were followed up until the earliest evidence of death, AVF maturation, or the end of 2014. RESULTS: In the study period, 45,087 new AVFs were placed in 39,820 prevalent hemodialysis patients. No evidence of use was identified for 36.2% of AVFs. Only 54.7% of AVFs were used within 4 months of placement, with maturation rates varying considerably across end-stage renal disease (ESRD) networks. Older age was associated with lower AVF maturation rates. Female sex, black race, some comorbid conditions (cardiovascular disease, peripheral artery disease, diabetes, needing assistance, or institutionalized status), dialysis vintage longer than 1 year, and catheter or arteriovenous graft use at ESRD incidence were also associated with lower rates of successful AVF maturation. In contrast, hypertension and prior AVF placement at ESRD incidence were associated with higher rates of successful AVF maturation. LIMITATIONS: This study relies on administrative data, with monthly recording of access use. CONCLUSIONS: We identified numerous associations between AVF maturation and patient-level factors in a recent national sample of US hemodialysis patients. After accounting for these patient factors, we observed substantial differences in AVF maturation across some ESRD networks, indicating a need for additional study of the provider, practice, and regional factors that explain AVF maturation.

Has dialysis payment reform led to initial racial disparities in anemia and mineral metabolism management?

Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in survey-weighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P<0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P<0.001), and mean serum PTH increased from 340 to 435 pg/ml (P<0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P>0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.

Stroke and the "stroke belt" in dialysis: contribution of patient characteristics to ischemic stroke rate and its geographic variation.

Geographic variation in stroke rates is well established in the general population, with higher rates in the South than in other areas of the United States. ESRD is a potent risk factor for stroke, but whether regional variations in stroke risk exist among dialysis patients is unknown. Medicare claims from 2000 to 2005 were used to ascertain ischemic stroke events in a large cohort of 265,685 incident dialysis patients. A Poisson generalized linear mixed model was generated to determine factors associated with stroke and to ascertain state-by-state geographic variability in stroke rates by generating observed-to-expected (O/E) adjusted rate ratios for stroke. Older age, female sex, African American race and Hispanic ethnicity, unemployed status, diabetes, hypertension, history of stroke, and permanent atrial fibrillation were positively associated with ischemic stroke, whereas body mass index >30 kg/m(2) was inversely associated with stroke (P<0.001 for each). After full multivariable adjustment, the three states with O/E rate ratios >1.0 were all in the South: North Carolina, Mississippi, and Oklahoma. Regional efforts to increase primary prevention in the "stroke belt" or to better educate dialysis patients on the signs of stroke so that they may promptly seek care may improve stroke care and outcomes in dialysis patients.

The prevalence of and factors associated with chronic atrial fibrillation in Medicare/Medicaid-eligible dialysis patients.

Atrial fibrillation is an important comorbidity with substantial therapeutic implications in dialysis patients but its prevalence varies in different studies. We used a database that includes patients in the United States on hemodialysis who were eligible for government assistance with prescription drugs. We then used ICD-9 codes from billing claims in this database to identify patients with chronic atrial fibrillation. Multivariable logistic regression was used to determine adjusted prevalence odds ratios for associated factors. Of 63,884 individuals, the prevalence of chronic atrial fibrillation was 7%. The factors of age over 60 years, male, Caucasian, body mass index over 25 kg/m(2), coronary artery disease, and heart failure were all significantly associated with chronic atrial fibrillation. Prevalence rates, particularly in younger patients, were far higher than those reported in an age group-matched nondialysis population. Thus, given its clinical impact, future efforts are needed to examine risk factors for adverse outcomes in chronic atrial fibrillation, and to identify appropriate management strategies for this disorder, as well as opportunities for quality improvement in this vulnerable population.

Geographic variation in HMG-CoA reductase inhibitor use in dialysis patients.

BACKGROUND: Despite uncertainty about their effectiveness in chronic dialysis patients, statin use has increased in recent years. Little is known about the demographic, clinical, and geographic factors associated with statin exposure in end-stage renal disease (ESRD) patients. OBJECTIVE: To analyze the demographic, clinical, and geographic factors associated with use of statins among chronic dialysis patients. DESIGN: Cross-sectional analysis. SETTING: Prevalent dialysis patients across the U.S. PARTICIPANTS: 55,573 chronic dialysis patients who were dually eligible for Medicaid and Medicare services during the last four months of 2005. METHODS: Using Medicaid prescription drug claims and United States Renal Data System core data, we examined demographics, comorbid conditions, and state of residence using hierarchical logistic regression models to determine their associations with statin use. INTERVENTION: Prescription for a statin. OUTCOME MEASURES: Factors associated with a prescription for a statin. RESULTS: Statin exposure was significantly associated with older age, female sex, Caucasian (versus African-American) race, body mass index, use of self-care dialysis, diabetes, and comorbidity burden. Moreover, there was substantial state-by-state variation in statin use, with a greater than 2.3-fold difference in adjusted odds ratios between the highest- and lowest-prescribing states. CONCLUSIONS: Among publicly insured chronic dialysis patients, there were marked differences between states in the use of HMG-CoA reductase inhibitors above and beyond patient characteristics. This suggests substantial clinical uncertainty about the utility of these medications. Understanding how such regional variations impact patient care in this high-risk population is an important focus for future work.

Association of race with cumulative exposure to statins in dialysis.

BACKGROUND: Patients on dialysis have high rates of cardiovascular disease and are frequently treated with HMG-CoA reductase inhibitors. Given that these patients have insurance coverage for medications as well as regular contact with health care providers, differences by race in exposure to statins over time should be minimal among patients who are candidates for the drug. METHODS: We created a cohort of incident dialysis patients who were dually eligible for Medicare and Medicaid services. We determined the proportion of days covered (or PDC, a marker of cumulative medication exposure) by a statin prescription over a mean of 2.0 ± 1.4 years. Ordinary least squares regression was used to determine the factors associated with cumulative drug exposure. RESULTS: Of the 18,727 patients who filled at least one prescription for a statin, mean PDC was 0.57 ± 0.32. The unadjusted PDC was higher for Caucasians (0.63 ± 0.31) than for African-Americans (0.51 ± 0.32), Hispanics (0.54 ± 0.31), and individuals of other race/ethnicity (0.58 ± 0.32). In multivariable modeling, Caucasian race was independently associated with greater exposure to statins. Relative to Caucasians, the adjusted odds ratios for the PDC for African-Americans was 0.47 (95% confidence interval, CI, 0.43-0.50), for Hispanics 0.52 (0.48-0.56) and for others, 0.72 (0.64-0.81). CONCLUSIONS: Despite insurance coverage, regular contact with health care providers, and at least one prescription for a statin, there are large differences by race in statin exposure over time. The provider- and patient-associated factors related to this phenomenon should be further examined.

Association of the Home Health Value-Based Purchasing Model With Quality, Utilization, and Medicare Payments After the First 5 Years.

Importance: The original Home Health Value-Based Purchasing (HHVBP) model provided financial incentives to home health agencies for quality improvement in 9 randomly selected US states. Objective: To evaluate quality, utilization, and Medicare payments for home health patients in HHVBP states compared with those in comparison states. Design, Setting, and Participants: This cohort study was conducted in 2021 with secondary data from January 2013 to December 2020. A difference-in-differences design and multivariate linear regression were used to compare outcomes for Medicare and Medicaid beneficiaries who received home health care in HHVBP states with those in 41 comparison states during 3 years of preintervention (2013-2015) and the subsequent 5 years (2016-2020). Exposures: Home health care provided by a home health agency in HHVBP states and comparison states. Main Outcomes and Measures: Utilization (unplanned hospitalizations, emergency department visits, skilled nursing facility [SNF] visits) for Medicare beneficiaries within 60 days of beginning home health, Medicare payments during and 37 days after home health episodes, and quality of care (functional status, patient experience) during home health episodes. Results: Among 34 058 796 home health episodes (16 584 870 beneficiaries; mean [SD] age of 76.6 [11.7] years; 60.5% female; 11.2% Black non-Hispanic; 79.5% White non-Hispanic) from January 2016 to December 2020, 22.6% were in HHVBP states and 77.4% were in non-HHVBP states. For the HHVBP and non-HHVBP groups, 60.4% and 61.0% of episodes were provided to female patients; 10.0% and 13.6% were provided to Black non-Hispanic patients, and 82.4% and 75.2% were provided to White non-Hispanic patients, respectively. Unplanned hospitalizations decreased by 0.15 percentage points (95% CI, -0.30 to -0.01) more in HHVBP states, a 1.0% decline compared with 15.7% at baseline. The use of SNFs decreased by 0.34 percentage points (95% CI, -0.40 to -0.27) more in HHVBP states, a 6.9% decline compared with the 4.9% baseline average. There was an association between HHVBP and a reduction in average Medicare payments per day of $2.17 (95% CI, -$3.67 to -$0.68) in HHVBP states, primarily associated with reduced inpatient and SNF services, which corresponded to an average annual Medicare savings of $190 million. There was greater functional improvement in HHVBP states than comparison states and no statistically significant change in emergency department use or most measures of patient experience. Conclusions and Relevance: In this cohort study, the HHVBP model was associated with lower Medicare payments that were associated with lower utilization of inpatient and SNF services, with better or similar quality of care.

Geographic variation in cardioprotective antihypertensive medication usage in dialysis patients.

BACKGROUND: Despite their high risk of adverse cardiac outcomes, persons on long-term dialysis therapy have had lower use of antihypertensive medications with cardioprotective properties, such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), ß-blockers, and calcium channel blockers, than might be expected. We constructed a novel database that permits detailed exploration into the demographic, clinical, and geographic factors associated with the use of these agents in hypertensive long-term dialysis patients. STUDY DESIGN: National cross-sectional retrospective analysis linking Medicaid prescription drug claims with US Renal Data System core data. SETTING & PARTICIPANTS: 48,882 hypertensive long-term dialysis patients who were dually eligible for Medicaid and Medicare services in 2005. FACTORS: Demographics, comorbid conditions, functional status, and state of residence. OUTCOMES: Prevalence of cardioprotective antihypertensive agents in Medicaid pharmacy claims and state-specific observed to expected ORs of medication exposure. MEASUREMENTS: Factors associated with medication use were modeled using multilevel logistic regression models. RESULTS: In multivariable analyses, cardioprotective antihypertensive medication exposure was associated significantly with younger age, female sex, nonwhite race, intact functional status, and use of in-center hemodialysis. Diabetes was associated with a statistically significant 28% higher odds of ACE-inhibitor/ARB use, but congestive heart failure was associated with only a 9% increase in the odds of ß-blocker use and no increase in ACE-inhibitor/ARB use. There was substantial state-by-state variation in the use of all classes of agents, with a greater than 2.9-fold difference in adjusted-rate ORs between the highest and lowest prescribing states for ACE inhibitors/ARBs and a 3.6-fold difference for ß-blockers. LIMITATIONS: Limited generalizability beyond study population. CONCLUSIONS: In publicly insured long-term dialysis patients with hypertension, there were marked differences in use rates by state, potentially due in part to differences in Medicaid benefits. However, geographic characteristics also were associated with exposure, suggesting clinical uncertainty about the utility of these medications.

Considering health insurance: how do dialysis initiates with Medicaid coverage differ from persons without Medicaid coverage?

BACKGROUND: Type of health insurance is an important mediator of medical outcomes in the United States. Medicaid, a jointly sponsored Federal/State programme, is designed to serve medically needy individuals. How these patients differ from non-Medicaid-enrolled incident dialysis patients and how these differences have changed over time have not been systematically examined. METHODS: Using data from the United States Renal Data System, we identified individuals initiating dialysis from 1995 to 2004 and categorized their health insurance status. Longitudinal trends in demographic, risk behaviour, functional, comorbidity, laboratory and dialysis modality factors, as reported on the Medical Evidence Form (CMS-2728), were examined in all insurance groups. Polychotomous logistic regression was used to estimate adjusted generalized ratios (AGRs) for these factors by insurance status, with Medicaid as the referent insurance group. RESULTS: Overall, males constitute a growing percentage of both Medicaid and non-Medicaid patients, but in contrast to other insurance groups, Medicaid has a higher proportion of females. Non-Caucasians also constitute a higher proportion of Medicaid patients than non-Medicaid patients. Body mass index increased in all groups over time, and all groups witnessed a significant decrease in initiation on peritoneal dialysis. Polychotomous regression showed generally lower AGRs for minorities, risk behaviours and functional status, and higher AGRs for males, employment and self-care dialysis, for non-Medicaid insurance relative to Medicaid. CONCLUSIONS: While many broad parallel trends are evident in both Medicaid and non-Medicaid incident dialysis patients, many important differences between these groups exist. These findings could have important implications for policy planners, providers and payers.

Peritoneal Dialysis and Mortality, Kidney Transplant, and Transition to Hemodialysis: Trends From 1996-2015 in the United States.

RATIONALE & OBJECTIVE: Transitions between dialysis modalities can be disruptive to care. Our goals were to evaluate rates of transition from peritoneal dialysis (PD) to in-center hemodialysis (HD), mortality, and transplantation among incident PD patients in the US Renal Data System from 1996 to 2015 and identify factors associated with these outcomes. STUDY DESIGN: Observational registry-based retrospective cohort study. SETTING & PARTICIPANTS: Medicare patients incident to end-stage renal disease (ESRD) from January 1, 1996, through December 31, 2011 (for adjusted analyses; through December 31, 2014, for unadjusted analyses), and treated with PD 1 or more days within 180 days of ESRD incidence (n = 173,533 for adjusted analyses; n = 219,787 for unadjusted analyses). EXPOSURE & PREDICTORS: Exposure: 1 or more days of PD. Predictors: patient- and facility-level characteristics obtained from Centers for Medicare & Medicaid Services Form 2728 and other data sources. OUTCOMES: Patients were followed up for 3 years until transition to in-center HD, death, or transplantation. ANALYTICAL APPROACH: Multivariable Cox regression was used to estimate hazards over time and associations with predictors. RESULTS: Compared with earlier cohorts, recent incident PD patient cohorts had lower rates of death (48% decline) and transition to in-center HD (13% decline). Among many other findings, we found that: (1) rates of transition to in-center HD and death were lowest in the 2008 to 2011 cohort, (2) longer time receiving PD was associated with higher mortality risk but lower risk for transition to in-center HD, and (3) larger PD programs (≥25 vs ≤6 patients) displayed lower risks for death and transition to in-center HD. LIMITATIONS: Data collected on Form 2728 are only at the time of ESRD incidence and do not provide information at the time of transition to in-center HD, death, or transplantation. CONCLUSIONS: Rates of transition from PD to in-center HD and death rates for PD patients decreased over time and were lowest in PD programs with 25 or more patients. Implications of the observed improved technique survival warrant further investigation, focusing on modifiable factors of center-level performance to create opportunities for improved patient outcomes.

Survival Among Incident Peritoneal Dialysis Versus Hemodialysis Patients Who Initiate With an Arteriovenous Fistula.

RATIONALE & OBJECTIVE: Comparisons of outcomes between in-center hemodialysis (HD) and peritoneal dialysis (PD) are confounded by selection bias because PD patients are typically younger and healthier and may have received longer predialysis care. We compared first-year survival between what we hypothesized were clinically equivalent groups; namely, patients who initiate maintenance HD using an arteriovenous fistula (AVF) and those selecting PD as their initial modality. STUDY DESIGN: Observational, registry-based, retrospective cohort study. SETTING & PARTICIPANTS: US Renal Data System data for 5 annual cohorts (2010-2014; n = 130,324) of incident HD with an AVF and incident PD patients. EXPOSURES AND PREDICTORS: Exposure was more than 1 day receiving PD or more than 1 day receiving HD with an AVF. Time at risk for both cohorts was determined for 12 consecutive 30-day segments, censoring for transplantation, loss to follow-up, or end of time. Predictors included patient-level characteristics obtained from Centers for Medicare & Medicaid Services 2728 Form and other data sources. OUTCOMES: Patient survival. ANALYTICAL APPROACH: Unadjusted and multivariable risk-adjusted HRs for death of HD versus PD patients, averaged over 2010 to 2014, were calculated. RESULTS: The HD cohort's average unadjusted mortality rate was consistently higher than for the PD cohort. The HR of HD versus PD was 1.25 (95% CI, 1.20-1.30) in the unadjusted model and 0.84 (95% CI, 0.80-0.87) in the adjusted model. However, multivariable risk-adjusted analyses showed the HR of HD versus PD for the first 90 days was 1.06 (95% CI, 0.98-1.14), decreasing to 0.74 (95% CI, 0.68-0.80) in the 270- to 360-day period. LIMITATIONS: Residual confounding due to selection bias inherent in dialysis modality choice and the observational study design. Form 2728 provides baseline data at dialysis incidence alone, but not over time. CONCLUSIONS: US patients receiving HD with an AVF appear to have a survival advantage over PD patients after 90 days of dialysis initiation after accounting for patient characteristics. These findings have implications in the choice of initial dialysis modality and vascular access for patients.

An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ.

INTRODUCTION: Human models of noninvasive breast tumors are limited, and the existing in vivo models do not mimic inter- and intratumoral heterogeneity. Ductal carcinoma in situ (DCIS) is the most common type (80%) of noninvasive breast lesions. The aim of this study was to develop an in vivo model whereby the natural progression of human DCIS might be reproduced and studied. To accomplish this goal, the intraductal human-in-mouse (HIM) transplantation model was developed. The resulting models, which mimicked some of the diversity of human noninvasive breast cancers in vivo, were used to show whether subtypes of human DCIS might contain distinct subpopulations of tumor-initiating cells. METHODS: The intraductal models were established by injection of human DCIS cell lines (MCF10DCIS.COM and SUM-225), as well as cells derived from a primary human DCIS (FSK-H7), directly into the primary mouse mammary ducts via cleaved nipple. Six to eight weeks after injections, whole-mount, hematoxylin and eosin, and immunofluorescence staining were performed to evaluate the type and extent of growth of the DCIS-like lesions. To identify tumor-initiating cells, putative human breast stem/progenitor subpopulations were sorted from MCF10DCIS.COM and SUM-225 with flow cytometry, and their in vivo growth fractions were compared with the Fisher's Exact test. RESULTS: Human DCIS cells initially grew within the mammary ducts, followed by progression to invasion in some cases into the stroma. The lesions were histologically almost identical to those of clinical human DCIS. This method was successful for growing DCIS cell lines (MCF10DCIS.COM and SUM-225) as well as a primary human DCIS (FSK-H7). MCF10DCIS.COM represented a basal-like DCIS model, whereas SUM-225 and FSK-H7 cells were models for HER-2+ DCIS. With this approach, we showed that various subtypes of human DCIS appeared to contain distinct subpopulations of tumor-initiating cells. CONCLUSIONS: The intraductal HIM transplantation model provides an invaluable tool that mimics human breast heterogeneity at the noninvasive stages and allows the study of the distinct molecular and cellular mechanisms of breast cancer progression.

Peritoneal Dialysis Patient Outcomes under the Medicare Expanded Dialysis Prospective Payment System.

BACKGROUND AND OBJECTIVES: Peritoneal dialysis (PD) use increased in the United States with the introduction of a new Medicare prospective payment system in January 2011 that likely reduced financial disincentives for facility use of this home therapy. The expansion of PD to a broader population and facilities having less PD experience may have implications for patient outcomes. We assessed the impact of PD expansion on PD discontinuation and patient mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective cohort study was conducted of patients treated with PD at 90 days of ESKD. Patients were grouped by study start date relative to the Medicare payment reform: prereform (July 1, 2008 to December 31, 2009; n=10,585), interim (January 1, 2010 to December 31, 2010; n=7832), and reform period (January 1, 2011 to December 31, 2012; n=18,742). Patient characteristics and facility PD experience were compared at baseline (day 91 of ESKD). Patients were followed for 3 years for the major outcomes of PD discontinuation and mortality using Cox proportional hazards models. RESULTS: Patient characteristics, including age, sex, race, ethnicity, rurality, cause of ESKD, and comorbidity, were similar or showed small changes across the three study periods. There was an increasing tendency for patients on PD to be treated in facilities with less PD experience (from 34% during the prereform period being treated in facilities averaging <14 patients on PD per year to 44% in the reform period). Patients treated in facilities with less PD experience had a higher rate of PD discontinuation than patients treated in facilities with the most experience (hazard ratio [HR], 1.16; 95% confidence interval [95% CI], 1.10 to 1.23 for the first versus fifth quintile of PD experience). Nevertheless, the risk of PD discontinuation fell during the late interim period (HR, 0.88; 95% CI, 0.82 to 0.95) and most of the reform period (from HR, 0.85; 95% CI, 0.79 to 0.91 to HR, 0.94; 95% CI, 0.87 to 1.01). Mortality risk was stable across the three study periods. CONCLUSIONS: In the context of expanding PD use and declining facility PD experience, the risk of PD discontinuation fell, and there was no adverse effect on mortality. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_12_CJN01610219.mp3.