Unintended Consequences of Health Care Reform: Impact of Changes in Payor Mix on Patient Safety Indicators.

OBJECTIVE: To evaluate the impact of the Affordable Care Act's Medicaid expansion on patient safety metrics at the hospital level by expansion status, across varying levels of safety-net burden, and over time. SUMMARY BACKGROUND DATA: Medicaid expansion has raised concerns over the influx of additional medically and socially complex populations on hospital systems. Whether increases in Medicaid and uninsured payor mix impact hospital performance metrics remains largely unknown. We sought to evaluate the effects of expansion on Centers for Medicare and Medicaid Services-endorsed Patient Safety Indicators (PSI-90). METHODS: Three hundred fifty-eight hospitals were identified using State Inpatient Databases (2012-2015) from 3 expansions (KY, MD, NJ) and 2 nonexpansion (FL, NC) states. PSI-90 scores were calculated using Agency for Healthcare Research and Quality modules. Hospital Medicaid and uninsured patients were categorized into safety-net burden (SNB) quartiles. Hospital-level, multivariate linear regression was performed to measure the effects of expansion and change in SNB on PSI-90. RESULTS: PSI-90 decreased (safety improved) over time across all hospitals (-5.2%), with comparable reductions in expansion versus nonexpansion states (-5.9% vs -4.7%, respectively; P = 0.441) and across high SNB hospitals within expansion versus nonexpansion states (-3.9% vs -5.2%, P = 0.639). Pre-ACA SNB quartile did not predict changes in PSI-90 post-ACA. However, when hospitals increased their SNB by 5%, they incurred significantly more safety events in expansion relative to nonexpansion states (+1.87% vs -14.0%, P = 0.013). CONCLUSIONS: Despite overall improvement in patient safety, increased SNB was associated with increased safety events in expansion states. Accordingly, Centers for Medicare and Medicaid Services measures may unintentionally penalize hospitals with increased SNB following Medicaid expansion.

SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. METHODS: This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. RESULTS: 412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC < 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC < 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC < 50%, 10.0 months, P = 0.39, respectively). CONCLUSIONS: PD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies. Trial registration ClinicalTrials.gov, NCT02543476. Registered September 4, 2015.

Utilization of Left Ventricular Assist Devices in Vulnerable Adults Across Medicaid Expansion.

BACKGROUND: Continuous-flow left ventricular assist device (LVAD) implantation is a payor sensitive procedure influenced by preoperative comorbidities and social factors. Whether expansion in insurance coverage will further influence device utilization is unknown. This study sought to assess the effects of Medicaid expansion on vulnerable populations (namely racial-ethnic minorities and those with low-income status) undergoing continuous-flow LVAD implantation after the enactment of the 2014 Affordable Care Act (ACA). METHODS: Data from the 2012 to Q3 2015 State Inpatient Database were used to examine a cohort of 624 nonelderly adults (aged 18-64 y) who were given a continuous-flow LVAD in three expansion states (Kentucky, New Jersey, and Maryland) and two nonexpansion states (North Carolina and Florida). The cohort excluded patients who had a heart transplant, heart-lung transplant, or noncontinuous-flow LVAD. Poisson Interrupted Time Series was used with three-way interactions and change of slope and intercept parameters at 2014 to determine the impact of the ACA expansion on utilization of continuous-flow LVAD by race and insurance strata. RESULTS: Poisson Interrupted Time Series models show that within expansion states, the population of Medicaid and uninsured patients saw an increase in the utilization of LVAD's immediately after ACA expansion, from 2.8 in Q4 2013 to 9.83 Q1 2014 (incidence rate ratio [IRR] 5.26, P = 0.02). Utilization eventually declined to pre-ACA levels, however, ending with 3.04 LVADs in Q3 2015 (IRR 0.84, 95% confidence interval 0.58-1.20). Models testing for racial effect showed no statistically preferential or disparate effects (immediate effect IRR 1.608, P = 0.506; marginal effect IRR 0.897, P = 0.512). CONCLUSIONS: These findings show that despite expanded insurance coverage, the utilization of continuous-flow LVADs was not increased in nonelderly racial and ethnic minorities following the ACA Medicaid expansion. Although these findings are preliminary and require further long-term evaluation, they suggest that insurance coverage alone does not play a significant role in increased utilization of continuous-flow LVAD. These findings point toward the importance of further exploring social, medical, and hospital drivers of these disparities.

Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.

Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 ± 9 years in both groups (P = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 ± 5.3 vs. 4.2 ± 3.3 years, P = 0.001). There were no significant differences in LVEF (P = 0.227) or GLS (P = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value <18.9 % was seen in 4 (10 %) BRCA1/2 mutation carriers and 7 (17 %) sporadic participants. In this first prospective examination of cardiac function in BRCA1/2 mutation carriers, we found no significant differences in sensitive echocardiographic parameters of cardiac function between BRCA1/2 mutation carriers and women with history of sporadic BC who received anthracycline treatment. In contrast to laboratory animal data, our findings indicate lack of elevated cardiac risk with the use of standard-doses of adjuvant anthracyclines in treatment of BRCA1/2 mutation carriers with early stage BC.

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative.

BACKGROUND: Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs). PREDICTORS: Categories of eGFR (exposure); race/ethnicity (effect modifier). OUTCOMES: The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death. MEASUREMENTS: We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. RESULTS: During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories. LIMITATIONS: Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. CONCLUSIONS: In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

Travel patterns of cancer surgery patients in a regionalized system.

BACKGROUND: Regionalization of complex surgeries has increased patient travel distances possibly leaving a substantial burden on those at risk for poorer surgical outcomes. To date, little is known about travel patterns of cancer surgery patients in regionalized settings. To inform this issue, we sought to assess travel patterns of those undergoing a major cancer surgery within a regionalized system. MATERIALS AND METHODS: We identified 4733 patients who underwent lung, esophageal, gastric, liver, pancreatic, and colorectal resections from 2002-2014 within a multihospital system in the Mid-Atlantic region of the United States. Patient age, race and/or ethnicity, and insurance status were extracted from electronic health records. We used Geographical Information System capabilities in R software to estimate travel distance and map patient addresses based on cancer surgery type and these characteristics. We used visual inspection, analysis of variance, and interaction analyses to assess the distribution of travel distances between patient populations. RESULTS: A total of 48.2% of patients were non-white, 49.9% were aged >65 y, and 54.9% had private insurance. Increased travel distance was associated with decreasing age and those undergoing pancreatic and esophageal resections. Also, black patients tend to travel shorter distances than other racial and/or ethnic groups. CONCLUSIONS: These maps offer a preliminary understanding into variations of geospatial travel patterns among patients receiving major cancer surgery in a Mid-Atlantic regionalized setting. Future research should focus on the impact of regionalization on timely delivery of surgical care and other quality metrics.

Postoperative wound dehiscence: Predictors and associations.

The Agency for Healthcare Research and Quality patient safety indicators (PSI) were developed as a metric of hospital complication rates. PSI-14 measures postoperative wound dehiscence and specifically how often a surgical wound in the abdominal or pelvic area fails to heal after abdominopelvic surgery. Wound dehiscence is estimated to occur in 0.5-3.4% of abdominopelvic surgeries, and carries a mortality of up to 40%. Postoperative wound dehiscence has been adopted as a surrogate safety outcome measure as it impacts morbidity, length of stay, healthcare costs and readmission rates. Postoperative wound dehiscence cases from the Nationwide Inpatient Sample demonstrate 9.6% excess mortality, 9.4 days of excess hospitalization and $40,323 in excess hospital charges relative to matched controls. The purpose of the current study was to investigate the associations between PSI-14 and measurable medical and surgical comorbidities using the Explorys technology platform to query electronic health record data from a large hospital system serving a diverse patient population in the Washington, DC and Baltimore, MD metropolitan areas. The study population included 25,636 eligible patients who had undergone abdominopelvic surgery between January 1, 2008 and December 31, 2012. Of these cases, 786 (2.97%) had postoperative wound dehiscence. Patient-associated comorbidities were strongly associated with PSI-14, suggesting that this indicator may not solely be an indicator of hospital safety. There was a strong association between PSI-14 and opioid use after surgery and this finding merits further investigation.

Activity, energy intake, obesity, and the risk of incident kidney stones in postmenopausal women: a report from the Women's Health Initiative.

Obesity is a strong risk factor for nephrolithiasis, but the role of physical activity and caloric intake remains poorly understood. We evaluated this relationship in 84,225 women with no history of stones as part of the Women's Health Initiative Observational Study, a longitudinal, prospective cohort of postmenopausal women enrolled from 1993 to 1998 with 8 years' median follow-up. The independent association of physical activity (metabolic equivalents [METs]/wk), calibrated dietary energy intake, and body mass index (BMI) with incident kidney stone development was evaluated after adjustment for nephrolithiasis risk factors. Activity intensity was evaluated in stratified analyses. Compared with the risk in inactive women, the risk of incident stones decreased by 16% in women with the lowest physical activity level (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [95% CI], 0.74 to 0.97). As activity increased, the risk of incident stones continued to decline until plateauing at a decrease of approximately 31% for activity levels ≥10 METs/wk (aHR, 0.69; 95% CI, 0.60 to 0.79). Intensity of activity was not associated with stone formation. As dietary energy intake increased, the risk of incident stones increased by up to 42% (aHR, 1.42; 95% CI, 1.02 to 1.98). However, intake <1800 kcal/d did not protect against stone formation. Higher BMI category was associated with increased risk of incident stones. In summary, physical activity may reduce the risk of incident kidney stones in postmenopausal women independent of caloric intake and BMI, primarily because of the amount of activity rather than exercise intensity. Higher caloric intake further increases the risk of incident stones.

Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing.

To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing.

Dietary intake of fiber, fruit and vegetables decreases the risk of incident kidney stones in women: a Women's Health Initiative report.

PURPOSE: We evaluated the relationship between dietary fiber, fruit and vegetable intake, and the risk of kidney stone formation. MATERIALS AND METHODS: Overall 83,922 postmenopausal women from the Women's Health Initiative observational study were included in the analysis and followed prospectively. Cox proportional hazards regression analyses were used to evaluate the associations between total dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity, geographic region, diabetes mellitus, calcium supplementation, hormone therapy use, body mass index and calibrated caloric intake; and dietary water, sodium, animal protein and calcium intake). Women with a history of kidney stones (3,471) were analyzed separately. RESULTS: Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney stone formation in separate adjusted models. In women with a history of stones there were no significant protective effects of fiber, fruit or vegetable intake on the risk of kidney stone recurrence. CONCLUSIONS: Greater dietary intake of fiber, fruits and vegetables was associated with a reduced risk of incident kidney stones in postmenopausal women. The protective effects were independent of other known risk factors for kidney stones. In contrast, there was no reduction in risk in women with a history of stones.

Use of Machine Learning for Early Detection of Maternal Cardiovascular Conditions: Retrospective Study Using Electronic Health Record Data.

BACKGROUND: Cardiovascular conditions (eg, cardiac and coronary conditions, hypertensive disorders of pregnancy, and cardiomyopathies) were the leading cause of maternal mortality between 2017 and 2019. The United States has the highest maternal mortality rate of any high-income nation, disproportionately impacting those who identify as non-Hispanic Black or Hispanic. Novel clinical approaches to the detection and diagnosis of cardiovascular conditions are therefore imperative. Emerging research is demonstrating that machine learning (ML) is a promising tool for detecting patients at increased risk for hypertensive disorders during pregnancy. However, additional studies are required to determine how integrating ML and big data, such as electronic health records (EHRs), can improve the identification of obstetric patients at higher risk of cardiovascular conditions. OBJECTIVE: This study aimed to evaluate the capability and timing of a proprietary ML algorithm, Healthy Outcomes for all Pregnancy Experiences-Cardiovascular-Risk Assessment Technology (HOPE-CAT), to detect maternal-related cardiovascular conditions and outcomes. METHODS: Retrospective data from the EHRs of a large health care system were investigated by HOPE-CAT in a virtual server environment. Deidentification of EHR data and standardization enabled HOPE-CAT to analyze data without pre-existing biases. The ML algorithm assessed risk factors selected by clinical experts in cardio-obstetrics, and the algorithm was iteratively trained using relevant literature and current standards of risk identification. After refinement of the algorithm's learned risk factors, risk profiles were generated for every patient including a designation of standard versus high risk. The profiles were individually paired with clinical outcomes pertaining to cardiovascular pregnancy conditions and complications, wherein a delta was calculated between the date of the risk profile and the actual diagnosis or intervention in the EHR. RESULTS: In total, 604 pregnancies resulting in birth had records or diagnoses that could be compared against the risk profile; the majority of patients identified as Black (n=482, 79.8%) and aged between 21 and 34 years (n=509, 84.4%). Preeclampsia (n=547, 90.6%) was the most common condition, followed by thromboembolism (n=16, 2.7%) and acute kidney disease or failure (n=13, 2.2%). The average delta was 56.8 (SD 69.7) days between the identification of risk factors by HOPE-CAT and the first date of diagnosis or intervention of a related condition reported in the EHR. HOPE-CAT showed the strongest performance in early risk detection of myocardial infarction at a delta of 65.7 (SD 81.4) days. CONCLUSIONS: This study provides additional evidence to support ML in obstetrical patients to enhance the early detection of cardiovascular conditions during pregnancy. ML can synthesize multiday patient presentations to enhance provider decision-making and potentially reduce maternal health disparities.

Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To investigate the relationship between chronic kidney disease (CKD) and MRI-defined cerebral microbleeds (CMB), a harbinger of future intracerebral hemorrhage (ICH), among patients with a recent history of primary ICH. METHODS: Using data from a predominantly black cohort of patients with a recent ICH-enrolled in an observational study between September 2007 and June 2011, we evaluated the association between CKD (defined as estimated low glomerular filtration rate<60 mL/min per 1.73 m(2)) and CMB on gradient-echo MRI. Multivariable models were generated to determine the contribution of CKD to the presence, number, and location of CMB. RESULTS: Of 197 subjects with imaging data, mean age was 59 years, 48% were women, 73% were black, 114 (58%) had ≥1 CMBs, and 52 (26%) had CKD. Overall, CKD was associated with presence of CMB (adjusted odds ratio, 2.70; 95% confidence interval [CI], 1.10-6.59) and number of CMB (adjusted relative risk, 2.04; 95% CI, 1.27-3.27). CKD was associated with CMB presence (adjusted odds ratio, 3.44; 95% CI, 1.64-7.24) and number (adjusted relative risk, 2.46; 95% CI, 1.11-5.42) in black patients, but not CMB presence (adjusted odds ratio, 3.00; 95% CI, 0.61-14.86) or number (adjusted relative risk, 1.03; 95% CI: 0.22-4.89) in non-Hispanic white patients (interactions by race were statistically not significant). CONCLUSIONS: CKD is associated with a greater presence and number of CMB in ICH patients, particularly in patients of black race. Future studies should assess whether low estimated glomerular filtration rate may be a CMB risk marker or potential therapeutic target for mitigating the development of CMB.

Predictors of highly prevalent brain ischemia in intracerebral hemorrhage.

OBJECTIVE: This study was undertaken to determine the prevalence, characteristics, risk factors, and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH). METHODS: Patients were recruited within a prospective, longitudinal, magnetic resonance imaging (MRI)-based study of primary ICH. Clinical, demographic, and MRI data were collected on all subjects at baseline and 1 month. RESULTS: Of the 138 patients enrolled, mean age was 59 years, 54% were male, 73% were black, and 84% had a history of hypertension. At baseline, ischemic lesions on diffusion-weighted imaging (DWI) were found in 35% of patients. At 1 month, lesions were present in 27%, and of these lesions, 83% were new and not present at baseline. ICH volume (p = 0.025), intraventricular hemorrhage (p = 0.019), presence of microbleeds (p = 0.024), and large, early reductions in mean arterial pressure (p = 0.003) were independent predictors of baseline DWI lesions. A multivariate logistical model predicting the presence of 1-month DWI lesions included history of any prior stroke (p = 0.012), presence of 1 or more microbleeds (p = 0.04), black race (p = 0.641), and presence of a DWI lesion at baseline (p = 0.007). INTERPRETATION: This study demonstrates that >⅓ of patients with primary ICH have active cerebral ischemia at baseline remote from the index hematoma, and » of patients experience ongoing, acute ischemic events at 1 month. Multivariate analyses implicate blood pressure reductions in the setting of an active vasculopathy as a potential underlying mechanism. Further studies are needed to determine the impact of these lesions on outcome and optimal management strategies to arrest vascular damage.

Chronic leg ulceration associated with polycythemia vera responding to ruxolitinib (Jakafi(®)).

We present the case of a 63-year-old white male with bilateral chronic leg ulcers due to polycythemia vera and hydroxyurea therapy who demonstrated dramatic healing of his wounds in response to ruxolitinib (Jakafi(®), Novartis), a novel Janus kinase-1 and -2 inhibitor. This patient's wound had previously been refractory to multiple surgical interventions and immunosuppression. After the initiation of ruxolitinib, the patient underwent successful split-thickness skin grafting, with resultant healing of his wounds. He was stable without prednisone and other immunosuppressant therapy and had healed at 6 months. Ruxolitinib therapy could represent a novel option for patients who develop persistent inflammatory wounds in the setting of polycythemia vera and hydroxyurea therapy.

Opioid use and opioid use disorder in mono and dual-system users of veteran affairs medical centers.

Introduction: Efforts to achieve opioid guideline concordant care may be undermined when patients access multiple opioid prescription sources. Limited data are available on the impact of dual-system sources of care on receipt of opioid medications. Objective: We examined whether dual-system use was associated with increased rates of new opioid prescriptions, continued opioid prescriptions and diagnoses of opioid use disorder (OUD). We hypothesized that dual-system use would be associated with increased odds for each outcome. Methods: This retrospective cohort study was conducted using Veterans Administration (VA) data from two facilities from 2015 to 2019, and included active patients, defined as Veterans who had at least one encounter in a calendar year (2015-2019). Dual-system use was defined as receipt of VA care as well as VA payment for community care (non-VA) services. Mono users were defined as those who only received VA services. There were 77,225 dual-system users, and 442,824 mono users. Outcomes were three binary measures: new opioid prescription, continued opioid prescription (i.e., received an additional opioid prescription), and OUD diagnosis (during the calendar year). We conducted a multivariate logistic regression accounting for the repeated observations on patient and intra-class correlations within patients. Results: Dual-system users were significantly younger than mono users, more likely to be women, and less likely to report white race. In adjusted models, dual-system users were significantly more likely to receive a new opioid prescription during the observation period [Odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.76-1.93], continue prescriptions (OR = 1.24, CI 1.22-1.27), and to receive an OUD diagnosis (OR = 1.20, CI 1.14-1.27). Discussion: The prevalence of opioid prescriptions has been declining in the US healthcare systems including VA, yet the prevalence of OUD has not been declining at the same rate. One potential problem is that detailed notes from non-VA visits are not immediately available to VA clinicians, and information about VA care is not readily available to non-VA sources. One implication of our findings is that better health system coordination is needed. Even though care was paid for by the VA and presumably closely monitored, dual-system users were more likely to have new and continued opioid prescriptions.

Poor long-term blood pressure control after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Hypertension is the most important risk factor associated with intracerebral hemorrhage. We explored racial differences in blood pressure (BP) control after intracerebral hemorrhage and assessed predictors of BP control at presentation, 30 days, and 1 year in a prospective cohort study. METHODS: Subjects with spontaneous intracerebral hemorrhage were identified from the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project. BP was compared by race at each time point. Multivariable linear regression was used to determine predictors of presenting mean arterial pressure, and longitudinal linear regression was used to assess predictors of mean arterial pressure at follow-up. RESULTS: A total of 162 patients were included (mean age, 59 years; 53% male; 77% black). Mean arterial pressure at presentation was 9.6 mm Hg higher in blacks than whites despite adjustment for confounders (P=0.065). Fewer than 20% of patients had normal BP (<120/80 mm Hg) at 30 days or 1 year. Although there was no difference at 30 days (P=0.331), blacks were more likely than whites to have Stage I/II hypertension at 1 year (P=0.036). Factors associated with lower mean arterial pressure at follow-up in multivariable analysis were being married at baseline (P=0.032) and living in a facility (versus personal residence) at the time of BP measurement (P=0.023). CONCLUSIONS: Long-term BP control is inadequate in patients after intracerebral hemorrhage, particularly in blacks. Further studies are needed to understand the role of social support and barriers to control to identify optimal approaches to improve BP in this high-risk population.

Arsenic exposure, diabetes prevalence, and diabetes control in the Strong Heart Study.

This study evaluated the association of arsenic exposure, as measured in urine, with diabetes prevalence, glycated hemoglobin, and insulin resistance in American Indian adults from Arizona, Oklahoma, and North and South Dakota (1989-1991). We studied 3,925 men and women 45-74 years of age with available urine arsenic measures. Diabetes was defined as a fasting glucose level of 126 mg/dL or higher, a 2-hour glucose level of 200 mg/dL or higher, a hemoglobin A1c (HbA1c) of 6.5% or higher, or diabetes treatment. Median urine arsenic concentration was 14.1 µg/L (interquartile range, 7.9-24.2). Diabetes prevalence was 49.4%. After adjustment for sociodemographic factors, diabetes risk factors, and urine creatinine, the prevalence ratio of diabetes comparing the 75th versus 25th percentiles of total arsenic concentrations was 1.14 (95% confidence interval: 1.08, 1.21). The association between arsenic and diabetes was restricted to participants with poor diabetes control (HbA1c ≥8%). Arsenic was positively associated with HbA1c levels in participants with diabetes. Arsenic was not associated with HbA1c or with insulin resistance (assessed by homeostatic model assessment to quantify insulin resistance) in participants without diabetes. Urine arsenic was associated with diabetes control in a population from rural communities in the United States with a high burden of diabetes. Prospective studies that evaluate the direction of the relation between poor diabetes control and arsenic exposure are needed.

The association of genetic variants of type 2 diabetes with kidney function.

Type 2 diabetes is highly prevalent and is the major cause of progressive chronic kidney disease in American Indians. Genome-wide association studies identified several loci associated with diabetes but their impact on susceptibility to diabetic complications is unknown. We studied the association of 18 type 2 diabetes genome-wide association single-nucleotide polymorphisms (SNPs) with estimated glomerular filtration rate (eGFR; MDRD equation) and urine albumin-to-creatinine ratio in 6958 Strong Heart Study family and cohort participants. Center-specific residuals of eGFR and log urine albumin-to-creatinine ratio, obtained from linear regression models adjusted for age, sex, and body mass index, were regressed onto SNP dosage using variance component models in family data and linear regression in unrelated individuals. Estimates were then combined across centers. Four diabetic loci were associated with eGFR and one locus with urine albumin-to-creatinine ratio. A SNP in the WFS1 gene (rs10010131) was associated with higher eGFR in younger individuals and with increased albuminuria. SNPs in the FTO, KCNJ11, and TCF7L2 genes were associated with lower eGFR, but not albuminuria, and were not significant in prospective analyses. Our findings suggest a shared genetic risk for type 2 diabetes and its kidney complications, and a potential role for WFS1 in early-onset diabetic nephropathy in American Indian populations.

Estimated GFR and incident cardiovascular disease events in American Indians: the Strong Heart Study.

BACKGROUND: In populations with high prevalences of diabetes and obesity, estimating glomerular filtration rate (GFR) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation may predict cardiovascular disease (CVD) risk better than by using the Modification of Diet in Renal Disease (MDRD) Study equation. STUDY DESIGN: Longitudinal cohort study comparing the association of GFR estimated using either the CKD-EPI or MDRD Study equation with incident CVD outcomes. SETTING & PARTICIPANTS: American Indians participating in the Strong Heart Study, a longitudinal population-based cohort with high prevalences of diabetes, CVD, and CKD. PREDICTOR: Estimated GFR (eGFR) predicted using the CKD-EPI and MDRD Study equations. OUTCOMES: Fatal and nonfatal cardiovascular events, consisting of coronary heart disease, stroke, and heart failure. MEASUREMENTS: The association between eGFR and outcomes was explored in Cox proportional hazards models adjusted for traditional risk factors and albuminuria; the net reclassification index and integrated discrimination improvement were determined for the CKD-EPI versus MDRD Study equations. RESULTS: In 4,549 participants, diabetes was present in 45%; CVD, in 7%; and stages 3-5 CKD, in 10%. During a median of 15 years, there were 1,280 cases of incident CVD, 929 cases of incident coronary heart disease, 305 cases of incident stroke, and 381 cases of incident heart failure. Reduced eGFR (<90 mL/min/1.73 m2) was associated with adverse events in most models. Compared with the MDRD Study equation, the CKD-EPI equation correctly reclassified 17.0% of 2,151 participants without incident CVD to a lower risk (higher eGFR) category and 1.3% (n=28) were reclassified incorrectly to a higher risk (lower eGFR) category. LIMITATIONS: Single measurements of eGFR and albuminuria at study visits. CONCLUSIONS: Although eGFR based on either equation had similar associations with incident CVD, coronary heart disease, stroke, and heart failure events, in those not having events, reclassification of participants to eGFR categories was superior using the CKD-EPI equation compared with the MDRD Study equation.