Investigation of the predictive value of a novel algorithm based on coronary CT angiography regarding fractional flow reserve and revascularization in patients with stable coronary artery disease.

Fractional flow reserve (FFR) has been established as a gold standard for functional coronary ischemia. At present, the FFR can be calculated from coronary computed tomography angiography (CCTA) images (CT-FFR). Previous studies have suggested that CT-FFR outperforms CCTA and invasive coronary angiography (ICA) in determining hemodynamic significance of stenoses. Recently, a novel automatical algorithm of CT-FFR called RuiXin-FFR has been developed. The present study is designed to investigate the predictive value of this algorithm and its value in therapeutic decision making. The present study retrospectively included 166 patients with stable coronary artery disease (CAD) who underwent CCTA screening and diagnostic ICA examination at Peking University People's Hospital, in 73 of whom wire-derived FFR was also measured. CT-FFR analyses were performed with a dedicated software. All patients were followed up for at least 1 year. We validated the accuracy of RuiXin-FFR with invasive FFR as the standard of reference, and investigated the role of RuiXin-FFR in predicting treatment strategy and long-term prognosis. The mean age of the patients was 63.3 years with 63.9% male. The CT-FFR showed a moderate correlation with wire-derived FFR (r = 0.542, p < 0.0001) and diagnostic accuracy of 87.6% to predict myocardial ischemia (AUC: 0.839, 95% CI 0.728-0.950), which was significantly higher than CCTA and ICA. In the multivariate logistic regression analysis, CT-FFR ≤ 0.80 was an independent predictor of undergoing coronary revascularization (OR: 45.54, 95% CI 12.03-172.38, p < 0.0001), whereas CT-FFR > 0.80 was an independent predictor of non-obstructive CAD (OR: 14.67, 95% CI 5.42-39.72, p < 0.0001). Reserving ICA and revascularization for vessels with positive CT-FFR could have reduced the rate of ICA by 29.6%, lowered the rate of ICA in vessels without stenosis > 50% by 11.7%, and increased the rate of revascularization in patients receiving ICA by 21.2%. The average follow-up was 23.7 months, and major adverse cardiovascular events (MACE) occurred in 11 patients. The rate of MACE was significantly lower in patients with CT-FFR > 0.80. The new algorithm of CT-FFR can be used to predict the invasive FFR. The RuiXin-FFR can also provide useful information for the screening of patients in whom further ICA is indeed needed and prognosis evaluation.

Identifying Individual and Clinic Characteristics Associated With Primary Care Provider Turnover During Implementation of the Veterans Health Administration Patient-Centered Medical Home.

Understanding which factors predict primary care provider (PCP) turnover can help organizations prepare for PCP shortages. We conducted a retrospective cohort study of Veteran Health Administration PCPs between 2012 and 2016. We analyzed whether 7 domains of the patient centered medical home (PCMH) implementation-including access, care coordination, comprehensiveness, self-management support, communication, shared decision-making, and team-based care-were associated with PCP turnover. We found that 2 domains of PCMH (access and self-management) were associated with lower turnover, which may reflect that practice cultures that support these characteristics may lower PCP turnover.

Incidence and predictors of left ventricular function change following ST-segment elevation myocardial infarction.

Aim: The purpose of the study was to assess the incidence and predictors of left ventricular function change in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Methods: 312 patients with STEMI who received primary percutaneous coronary intervention (PCI) between January 2015 and December 2016 were consecutively enrolled in this study. Multiple logistic regression analysis was used to evaluate independent predictors of left ventricular ejection fraction (LVEF) improvement after long-term follow-up. Results: We finally analyzed the LVEF change in 186 patients from baseline to follow-up. The mean age was 61.3 ± 12.5 years, with 78.5% being male. The median duration of follow-up after STEMI was 1,021 (389-1,947) days. 54.3% had a decrease in LVEF and 45.7% experienced an improvement in LV function after primary PCI through long-term follow-up. Logistic regression analysis showed lower peak troponin I, non-anterior STEMI, lower baseline LVEF, and no previous myocardial infarction history were independently associated with LVEF improvement. Conclusion: 54.3% of patients with STEMI undergoing primary PCI had a decrease in LVEF during long-term follow-up. LVEF recovery can be predicted by baseline characteristics.

A novel optical coherence tomography­based calcium scoring system can predict the stent expansion of moderate and severe calcified lesions.

Coronary calcified lesions can exert serious effects on stent expansion. A calcium scoring system, based on optical coherence tomography (OCT), has been previously developed to identify relatively mild calcified lesions that would benefit from plaque modification procedures. Therefore, the present study aimed to establish a novel OCT-based scoring system to predict the stent expansion of moderate and severe calcified lesions. A total of 33 patients who underwent percutaneous coronary intervention (PCI; 34 calcified lesions were observed using coronary angiography) were retrospectively included in the present study. Coronary angiography and OCT images were subsequently reviewed and analyzed. Furthermore, a calcium scoring system was developed based on the results of multivariate analysis before the optimal threshold for the prediction of stent underexpansion in patients with moderate and severe calcified lesions was determined. The mean age of the patients was 67±10 years. The present analysis demonstrated that the final post-PCI median stent expansion was 70.74%, where stent underexpansion (defined as stent expansion <80%) was observed in 23 lesions. The mean maximum calcium arc, length and thickness, which were assessed using OCT, were found to be 230˚, 25.10 mm and 1.18 mm, respectively. A multivariate logistic regression model demonstrated that age and the maximum calcium arc were independent predictors of stent underexpansion. A novel calcium scoring system was thereafter established using the following formula: (0.16 x age) + (0.03 x maximum calcium arc) according to the ß-coefficients in the multivariate analysis, with the optimal cut-off value for the prediction of stent underexpansion being 16.87. Receiver operating characteristic curve analysis demonstrated that this novel scoring system yielded a larger area under the curve value compared with that from a previous study's scoring system. Therefore, in conclusion, since the calcium scoring system of the present study based on age and the maximum calcium arc obtained from OCT was specifically developed in the subjects with moderate and severe calcified lesions, it may be more accurate in predicting the risk of stent underexpansion in these patients.

Potential drug-drug interactions in drug therapy for older adults with chronic coronary syndrome at hospital discharge: A real-world study.

Introduction: Polypharmacy are commonly observed among older adults with cardiovascular disease. However, multiple medications lead to increased risk of drug-drug interactions (DDIs). Therefore, identification and prevention actions related to harmful DDIs are expected in older adults. The study aimed to describe the prevalence of potential DDIs (pDDIs) in discharge prescriptions among older adults with chronic coronary syndrome (CCS). Methods: A single-center cross-sectional study was performed in a tertiary public hospital in Beijing, China. CCS patients aged 65 years and above who were admitted to cardiology wards over a 3-month period and alive at discharge were included. Electronic medical records and discharge prescriptions were reviewed. pDDIs were evaluated through the Lexi-Interact online. Results: pDDIs were identified in 72.9% of the 402 individuals (n = 293). A total of 864 pDDIs were obtained. 72.1% of patients were found with C DDIs (n = 290) and 20.3% were categorized in D and X DDIs (n = 82). The only X DDI was between cyclosporine and atorvastatin. Under category D, glycemia alterations within antidiabetics and increased chances of bleeding with antithrombotic were the most common. Concomitant use of clopidogrel and calcium channel blockers was a frequent situation within category C, followed by synergic blood pressure lowering agents and increased rosuvastatin concentration induced by clopidogrel. Conclusion: DDIs exposure was common in older CCS. DDIs screening tools should be introduced to alert potential adverse effects. Prescribers need to rigorously review or modulate therapies to prevent DDI-related adverse outcomes. Clinical pharmacists should be more involved in complex drug regimen management.

How Did Veterans' Reliance on Veterans Health Administration Outpatient Care Change After Expansion of the Veterans Community Care Program?

BACKGROUND: The Veterans Community Care Program (VCCP) aims to address access constraints in the Veterans Health Administration (VA) by reimbursing care from non-VA community providers. Little existing research explores how veterans' choice of VA versus VCCP providers has evolved as a significant VCCP expansion in 2014 as part of the Veterans Access, Choice, and Accountability Act. OBJECTIVES: We examined changes in reliance on VA for primary care (PC), mental health (MH), and specialty care (SC) among VCCP-eligible veterans. RESEARCH DESIGN: We linked VA administrative data with VCCP claims to retrospectively examine utilization during calendar years 2016-2018. SUBJECTS: 1.78 million veterans enrolled in VA before 2013 and VCCP-eligible in 2016 due to limited VA capacity or travel hardship. MEASURES: We measured reliance as the proportion of total annual outpatient (VA+VCCP) visits occurring in VA for PC, MH, and SC. RESULTS: Of the 26.1 million total outpatient visits identified, 45.6% were for MH, 29.9% for PC, and 24.4% for SC. Over the 3 years, 83.2% of veterans used any VA services, 23.8% used any VCCP services, and 20.0% were dual VA-VCCP users. Modest but statistically significant declines in reliance were observed from 2016-2018 for PC (94.5%-92.2%), and MH (97.8%-96.9%), and a more significant decline was observed for SC (88.5%-79.8%). CONCLUSIONS: Veterans who have the option of selecting between VA or VCCP providers continued using VA for most of their outpatient care in the initial years after the 2014 VCCP expansion.

The Coronary Angiography-Derived Index of Microcirculatory Resistance Predicts Left Ventricular Performance Recovery in Patients with ST-Segment Elevation Myocardial Infarction.

Objectives: The present study is designed to investigate the impact of coronary angiography-derived index of microcirculatory resistance (caIMR) on left ventricular performance recovery. Background: IMR has been established as a gold standard for coronary microvascular assessment and a predictor of left ventricular recovery after ST-segment elevation myocardial infarction (STEMI). CaIMR is a novel and accurate alternative of IMR. Methods: The present study retrospectively included 80 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). We offline performed the post-PCI caIMR analysis of the culprit vessel. Echocardiography was performed within the first 24 hours and at 3 months after the index procedure. Left ventricular recovery was defined as the change in left ventricular ejection fraction (LVEF) more than zero. Results: The mean age of the patients was 58.0 years with 80.0% male. The average post-PCI caIMR was 43.2. Overall left ventricular recovery was seen in 41 patients. Post-PCI caIMR (OR: 0.948, 95% CI: 0.916-0.981, p = 0.002), left anterior descending as the culprit vessel (OR: 3.605, 95% CI: 1.23-10.567, p = 0.019), and male (OR: 0.254, 95% CI: 0.066-0.979, p = 0.047) were independent predictors of left ventricular recovery at 3 months follow-up. A predictive model was established with the best cutoff value for the prediction of left ventricular recovery 2.33 (sensitivity 0.610, specificity 0.897, and area under the curve 0.765). In patients with a predictive model score less than 2.33, the LVEF increased significantly at 3 months. Conclusions: The post-PCI caIMR can accurately predict left ventricular functional recovery at 3 months follow-up in patients with STEMI treated by primary PCI, supporting its use in clinical practice.

The Effect of Bariatric Surgery on Long-term Depression Treatment in Patients With Obesity.

OBJECTIVE: In a large multisite cohort of Veterans who underwent Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (LSG), initiation of (ie, incident) and persistence of (ie, continuation of preoperative) depression treatment are compared with matched nonsurgical controls. BACKGROUND: Bariatric surgery has been associated with short-term improvements in depression but less is known about longer term outcomes. METHODS: In a retrospective cohort study, we matched 1713 Veterans with depression treatment who underwent bariatric surgery in Veterans Administration bariatric centers from fiscal year 2001 to 2016 to 15,056 nonsurgical controls using sequential stratification and examined the persistence of depression treatment via generalized estimating equations. Incidence of depression treatment was compared using Cox regression models between 2227 surgical patients and 20,939 matched nonsurgical controls without depression treatment at baseline. RESULTS: In surgical patients with depression treatment at baseline, the use of postsurgical depression treatment declined over time for both surgical procedures, but postsurgical patients had greater use of depression treatment at 5 years [RYGB: odds ratio=1.24, 95% confidence interval (CI): 1.04-1.49; LSG: odds ratio=1.27, 95% CI: 1.04-1.56] compared with controls. Among those without depression treatment at baseline, bariatric surgery was associated with a higher incidence of depression treatment compared with matched controls (RYGB: hazard ratio=1.34, 95% CI: 1.17-1.53; LSG: hazard ratio at 1-5 years=1.27, 95% CI: 1.10-1.47). CONCLUSIONS: Bariatric surgery was associated with a greater risk of postoperative incident depression treatment and greater persistence of postoperative depression treatment. Depression may worsen for some patients after bariatric surgery, so clinicians should carefully monitor their patients for depression postoperatively.

Successful Therapy for Myocarditis Concomitant With Complete Heart Block After Pembrolizumab Treatment for Head and Neck Squamous Cell Carcinoma: A Case Report With Literature Review.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy over the past decade. Despite their beneficial effects on treating numerous types of tumors, cardiotoxicity resulting from ICIs is a rare side effect but a concerning one due to its high mortality rate. We herein describe a case of an 80-year-old woman with recurrent head and neck squamous cell cancer (HNSCC), who presented with myocarditis complicated by complete atrioventricular block (CAVB) after second infusion of pembrolizumab. After quickly ruling out myocardial infarction and viral myocarditis, the strong relationship between the onset time and pembrolizumab therapy suggested that ICI-induced myocarditis was the most possible diagnosis. Though CAVB frequently presents with fulminant myocarditis in the setting of ICI-related cardiotoxicity, the patients kept a stable hemodynamic status and had normal myocardial function with just a slightly low global longitudinal strain (GLS) at-16.4%, which implied myocardial injury but was highly related to good prognosis based on the existing literature. Besides, elderly patients are vulnerable to adverse outcomes of steroid therapy, notably opportunistic infections. To balance beneficial effects and adverse effects of immune suppression, she accepted high-dose steroids without pulse methylprednisolone. Excitingly, she had a dramatic clinical and laboratory improvement, and heart block quickly returned to normal sinus rhythm. Another interesting finding was that the patient's tumor remained stable during the half-year follow-up from the termination of immunotherapy. Besides, we here firstly review previously reported cases in terms of their clinical characteristics and prognosis of ICI-induced myocarditis with CAVB, in particular the reversibility of heart block. In conclusion, ICI-induced myocarditis can be life-threatening and it therefore warrants efforts to increase awareness, facilitate early detection, and initiate prompt intervention. Importantly, CAVB secondary to ICIs-induced myocarditis may not always present with fulminant myocarditis and more than 50% of these surviving patients might recover to normal sinus rhythm. For patients with ICI-induced myocarditis with contraindication for cardiac magnetic resonance (CMR), speckle-tracking echocardiography is a reliable and sensitive alternative to CMR for detecting myocardial injury, and GLS may be an important prognostic indicator.

PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction.

Background and Objectives: Early diagnosis of patients with acute myocardial infarction (AMI) who are at a high risk of heart failure (HF) progression remains controversial. This study aimed at identifying new predictive biomarkers of post-AMI HF and at revealing the pathogenesis of HF involving these marker genes. Methods and Results: A transcriptomic dataset of whole blood cells from AMI patients with HF progression (post-AMI HF, n = 16) and without progression (post-AMI non-HF, n = 16) was analyzed using the weighted gene co-expression network analysis (WGCNA). The results indicated that one module consisting of 720 hub genes was significantly correlated with post-AMI HF. The hub genes were validated in another transcriptomic dataset of peripheral blood mononuclear cells (post-AMI HF, n = 9; post-AMI non-HF, n = 8). PRKAR1A, SDCBP, SPRED2, and VAMP3 were upregulated in the two datasets. Based on a single-cell RNA sequencing dataset of leukocytes from heart tissues of normal and infarcted mice, PRKAR1A was further verified to be upregulated in monocytes/macrophages on day 2, while SDCBP was highly expressed in neutrophils on day 2 and in monocytes/macrophages on day 3 after AMI. Cell-cell communication analysis via the "CellChat" package showed that, based on the interaction of ligand-receptor (L-R) pairs, there were increased autocrine/paracrine cross-talk networks of monocytes/macrophages and neutrophils in the acute stage of MI. Functional enrichment analysis of the abovementioned L-R genes together with PRKAR1A and SDCBP performed through the Metascape platform suggested that PRKAR1A and SDCBP were mainly involved in inflammation, apoptosis, and angiogenesis. The receiver operating characteristic (ROC) curve analysis demonstrated that PRKAR1A and SDCBP, as well as their combination, had a promising prognostic value in the identification of AMI patients who were at a high risk of HF progression. Conclusion: This study identified that PRKAR1A and SDCBP may serve as novel biomarkers for the early diagnosis of post-AMI HF and also revealed their potentially regulatory mechanism during HF progression.

Does Long-Term Post-Bariatric Weight Change Differ Across Antidepressants?

We sought to evaluate whether weight change up to 5 years after bariatric surgery differed by antidepressant class taken before surgery. Background: Bariatric surgery induces significant weight loss, but outcomes are highly variable. The specific type of antidepressant used prior to surgery may be an important factor in long-term weight loss. Methods: This retrospective cohort study from 2000 to 2016 compared the 5-year weight loss of 556 Veterans who were taking antidepressant monotherapy (bupropion, selective serotonin reuptake inhibitors [SSRIs], or serotonin-norepinephrine reuptake inhibitors [SNRIs]) before bariatric surgery (229 sleeve gastrectomy and 327 Roux-en-Y gastric bypass) versus 556 matched nonsurgical controls. Results: Patients taking bupropion before sleeve gastrectomy had greater differential weight loss between surgical patients and matched controls than those taking SSRIs at 1 (8.9 pounds; 95% confidence interval [CI], 1.6-16.3; P = 0.02) and 2 years (17.6 pounds; 95% CI, 5.9-29.3; P = 0.003), but there was no difference at 5 years (11.9 pounds; 95% CI, -8.9 to 32.8; P = 0.26). Findings were similar for gastric bypass patients taking bupropion compared to SSRIs at 1 (9.7 pounds; 95% CI, 2.0-17.4; P = 0.014), 2 (12.0 pounds; 95% CI, -0.5 to 24.5; P = 0.06), and 5 years (4.8 pounds; 95% CI, -16.7 to 26.3; P = 0.66). No significant differences were observed comparing patients taking SNRI versus SSRI medications. Conclusions: Sleeve gastrectomy and gastric bypass patients taking bupropion had greater weight loss than those taking SSRIs, although these differences may wane over time. Bupropion may be the first-line antidepressant of choice among patients with severe obesity considering bariatric surgery.

Economic costs of implementing evidence-based telemedicine outreach for posttraumatic stress disorder in VA.

Background: Telemedicine outreach for posttraumatic stress disorder (TOP) is a virtual evidence-based practice (EBP) involving telephone care management and telepsychology that engages rural patients in trauma-focused psychotherapy. This evaluation examined implementation and intervention costs attributable to deploying TOP from a health system perspective. Methods: Costs were ascertained as part of a stepped wedge cluster randomized trial at five sites within the Veterans Affairs (VA) Healthcare System. All sites initially received a standard implementation strategy, which included internal facilitation, dissemination of an internal facilitators operational guide, funded care manager, care managing training, and technical support. A subset of clinics that failed to meet performance metrics were subsequently randomized to enhanced implementation, which added external facilitation that focused on incorporating TOP clinical processes into existing clinic workflow. We measured site-level implementation activities using project records and structured activity logs tracking personnel-level time devoted to all implementation activities. We monetized time devoted to implementation activities by applying an opportunity cost approach. Intervention costs were measured as accounting-based costs for telepsychiatry/telepsychology and care manager visits, ascertained using VA administrative data. We conducted descriptive analyses of strategy-specific implementation costs across five sites. Descriptive analyses were conducted instead of population-level cost-effectiveness analysis because previous research found enhanced implementation was not more successful than the standard implementation in improving uptake of TOP. Results: Over the 40-month study period, four of five sites received enhanced implementation. Mean site-level implementation cost per month was $919 (SD = $238) during standard implementation and increased to $1,651 (SD = $460) during enhanced implementation. Mean site-level intervention cost per patient-month was $46 (SD = $28) during standard implementation and $31 (SD = $21) during enhanced implementation. Conclusions: Project findings inform the expected cost of implementing TOP, which represents one factor health systems should consider in the decision to broadly adopt this EBP. Plain Language Summary: What is already known about the topic: Trauma-focused psychotherapy delivered through telemedicine has been demonstrated as an effective approach for the treatment of post-traumatic stress disorder (PTSD). However, uptake of this evidence-based approach by integrated health systems such as the Veterans Affairs (VA) Health Care System is low. What does this paper add: This paper presents new findings on the costs of two implementation approaches designed to increase adoption telemedicine outreach for PTSD from a health system perspective. What are the implications for practice, research, and policy: Cost estimates from this paper can be used by health systems to inform the relative value of candidate implementation strategies to increase adoption of evidence-based treatments for PTSD or other mental health conditions.

Cardiovascular Magnetic Resonance Imaging and Heart Failure.

PURPOSE OF REVIEW: The purpose of this review is to summarize the application of cardiac magnetic resonance (CMR) in the diagnostic and prognostic evaluation of patients with heart failure (HF). RECENT FINDINGS: CMR is an important non-invasive imaging modality in the assessment of ventricular volumes and function and in the analysis of myocardial tissue characteristics. The information derived from CMR provides a comprehensive evaluation of HF. Its unique ability of tissue characterization not only helps to reveal the underlying etiologies of HF but also offers incremental prognostic information. CMR is a useful non-invasive tool for the diagnosis and assessment of prognosis in patients suffering from heart failure.

Identification of monocyte-associated genes as predictive biomarkers of heart failure after acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF. METHODS: We performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above. RESULTS: In our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients. CONCLUSION: Our findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.

Burden and Cost of Caring for US Veterans With CKD: Initial Findings From the VA Renal Information System (VA-REINS).

Kidney disease is a common, complex, costly, and life-limiting condition. Most kidney disease registries or information systems have been limited to single institutions or regions. A national US Department of Veterans Affairs (VA) Renal Information System (VA-REINS) was recently developed. We describe its creation and present key initial findings related to chronic kidney disease (CKD) without kidney replacement therapy (KRT). Data from the VA's Corporate Data Warehouse were processed and linked with national Medicare data for patients with CKD receiving KRT. Operational definitions for VA user, CKD, acute kidney injury, and kidney failure were developed. Among 7 million VA users in fiscal year 2014, CKD was identified using either a strict or liberal operational definition in 1.1 million (16.4%) and 2.5 million (36.3%) veterans, respectively. Most were identified using an estimated glomerular filtration rate laboratory phenotype, some through proteinuria assessment, and very few through International Classification of Diseases, Ninth Revision coding. The VA spent ∼$18 billion for the care of patients with CKD without KRT, most of which was for CKD stage 3, with higher per-patient costs by CKD stage. VA-REINS can be leveraged for disease surveillance, population health management, and improving the quality and value of care, thereby enhancing VA's capacity as a patient-centered learning health system for US veterans.

Thematic Analysis of the Health Records of a National Sample of US Veterans With Advanced Kidney Disease Evaluated for Transplant.

Importance: To be considered for a kidney transplant, patients with advanced kidney disease must participate in a formal evaluation and selection process. Little is known about how this process proceeds in real-world clinical settings. Objective: To characterize the transplant evaluation process among a representative national sample of US veterans with advanced kidney disease who were referred to a kidney transplant center. Design, Setting, and Participants: This qualitative study was a thematic analysis of clinician notes in the electronic health records of US veterans referred for kidney transplant evaluation. In a random sample of 4000 patients with advanced kidney disease between January 1, 2004, and December 31, 2014, cared for in the US Department of Veterans Affairs (VA) health care system, there were 211 patients who were referred to a transplant center during the follow-up period. This group was included in the qualitative analysis and was followed up until their date of death or the end of the follow-up period on October 8, 2019. Main Outcomes and Measures: Dominant themes pertaining to the kidney transplant evaluation and selection process identified through thematic analysis. Results: Among 211 study patients, the mean (SD) age was 57.9 (9.5) years, and 202 patients (95.7%) were male. The following 4 dominant themes regarding the transplant evaluation process emerged: (1) far-reaching and inflexible medical evaluation, in which patients were expected to complete an extensive evaluation that could have substantial physical and emotional consequences, made little accommodation for their personal values and needs, and impacted other aspects of their care; (2) psychosocial valuation, in which the psychosocial component of the transplant assessment could be subjective and intrusive and could place substantial demands on patients' family members; (3) surveillance over compliance, in which the patients' ability and willingness to follow medical recommendations was an important criterion for transplant candidacy and their adherence to a wide range of recommendations and treatments was closely monitored; and (4) disempowerment and lack of transparency, in which patients and their local clinicians were often unsure about what to expect during the evaluation process or about the rationale for selection decisions. For the evaluation process to proceed, local clinicians had to follow transplant center requirements even when they believed the requirements did not align with best practices or the patients' needs. Conclusions and Relevance: In this qualitative study of US veterans with advanced kidney disease evaluated for transplant, clinician documentation in the medical record indicated that, to be considered for a kidney transplant, patients were required to participate in a rigid, demanding, and opaque evaluation and selection process over which they and their local clinicians had little control. These findings highlight the need for a more evidence-based, individualized, and collaborative approach to kidney transplant evaluation.

Association of Bariatric Surgical Procedures With Changes in Unhealthy Alcohol Use Among US Veterans.

Importance: Bariatric surgical procedures have been associated with increased risk of unhealthy alcohol use, but no previous research has evaluated the long-term alcohol-related risks after laparoscopic sleeve gastrectomy (LSG), currently the most used bariatric procedure. No US-based study has compared long-term alcohol-related outcomes between patients who have undergone Roux-en-Y gastric bypass (RYGB) and those who have not. Objective: To evaluate the changes over time in alcohol use and unhealthy alcohol use from 2 years before to 8 years after a bariatric surgical procedure among individuals with or without preoperative unhealthy alcohol use. Design, Setting, and Participants: This retrospective cohort study analyzed electronic health record (EHR) data on military veterans who underwent a bariatric surgical procedure at any of the bariatric centers in the US Department of Veterans Affairs (VA) health system between October 1, 2008, and September 30, 2016. Surgical patients without unhealthy alcohol use at baseline were matched using sequential stratification to nonsurgical control patients without unhealthy alcohol use at baseline, and surgical patients with unhealthy alcohol use at baseline were matched to nonsurgical patients with unhealthy alcohol use at baseline. Data were analyzed in February 2020. Interventions: LSG (n = 1684) and RYGB (n = 924). Main Outcomes and Measures: Mean alcohol use, unhealthy alcohol use, and no alcohol use were estimated using scores from the validated 3-item Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), which had been documented in the VA EHR. Alcohol outcomes were estimated with mixed-effects models. Results: A total of 2608 surgical patients were included in the final cohort (1964 male [75.3%] and 644 female [24.7%] veterans. Mean (SD) age of surgical patients was 53.0 (9.9) years and 53.6 (9.9) years for the matched nonsurgical patients. Among patients without baseline unhealthy alcohol use, 1539 patients who underwent an LSG were matched to 14 555 nonsurgical control patients and 854 patients who underwent an RYGB were matched to 8038 nonsurgical control patients. In patients without baseline unhealthy alcohol use, the mean AUDIT-C scores and the probability of unhealthy alcohol use both increased significantly 3 to 8 years after an LSG or an RYGB, compared with control patients. Eight years after an LSG, the probability of unhealthy alcohol use was higher in surgical vs control patients (7.9% [95% CI, 6.4-9.5] vs 4.5% [95% CI, 4.1-4.9]; difference, 3.4% [95% CI, 1.8-5.0])). Similarly, 8 years after an RYGB, the probability of unhealthy alcohol use was higher in surgical vs control patients (9.2% [95% CI, 8.0-10.3] vs 4.4% [95% CI, 4.1-4.6]; difference, 4.8% [95% CI, 3.6-5.9]). The probability of no alcohol use also decreased significantly 5 to 8 years after both procedures for surgical vs control patients. Among patients with unhealthy alcohol use at baseline, prevalence of unhealthy alcohol use was higher for patients who underwent an RYGB than matched controls. Conclusions and Relevance: In this multi-site cohort study of predominantly male patients, among those who did not have unhealthy alcohol use in the 2 years before bariatric surgery, the probability of developing unhealthy alcohol use increased significantly 3-8 years after bariatric procedures compared with matched controls during follow-up.

Comparable, but distinct: Perceptions of primary care provided by physicians and nurse practitioners in full and restricted practice authority states.

AIMS: To understand patients' and providers' perceptions of primary care delivered by nurse practitioners (NPs) in the Veterans Affairs Healthcare System. DESIGN: Qualitative exploratory study (in convergent mixed-methods design). METHODS: Semi-structured interviews in 2016 with primary care providers and patients from facilities in states with full and restricted practice authority for NPs. Patient sample based on reassignment to: (a) a NP; or (b) a different physician following an established physician relationship. Data were analysed using content analysis. RESULTS: We interviewed 28 patients, 17 physicians and 14 NPs. We found: (a) NPs provided more holistic care than physicians; (b) patients were satisfied with NPs; and (c) providers' professional experience outweighed provider type. CONCLUSIONS: Patients' preferences for NPs (compared with prior physicians) contributed to perceptions of patient centredness. Similarities in providers' perceptions suggest NPs and physicians are both viable providers for primary care. IMPACT: Nurse Practitioners (NPs): practice authority Veterans Affairs Health care: nurse practitioners will continue to be a viable resource for primary care delivery United States Health care: challenges notions patients may not be satisfied with care provided by NPs and supports expanding their use to provide much-needed access to primary care services; expanding Full Practice Authority would allow states to provide acceptable primary care without diminishing patient or provider experiences.

Decreased miR­92a­3p expression potentially mediates the pro­angiogenic effects of oxidative stress­activated endothelial cell­derived exosomes by targeting tissue factor.

Angiogenesis is an essential pathological feature of vulnerable atherosclerotic plaque. Exosome­derived microRNAs (miRNAs or miRs) have been proven to be important regulators of angiogenesis. However, the role of exosomes, which are secreted by endothelial cells (ECs) under conditions of oxidative stress, in angiogenesis remain unclear. The present study aimed to investigate the effects and mechanism of oxidative stress­activated endothelial­derived exosomes in angiogenesis. Exosomes were isolated from H2O2­stimulated human umbilical vein ECs (HUVECs; termed Exo-H2O2) by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. Exo-H2O2 enhanced HUVEC proliferation, migration and tube formation, as determined by EdU incorporation assay, scratch wound migration assay and tube formation assay, respectively. miR­92a­3p was identified as the predominantly downregulated miRNA in the Exo-H2O2­treated HUVECs by small RNA sequencing, and the expression of primary miR­92a (pri­miR­92a­1) was also decreased, as shown by RT­qPCR. Similarly, the inhibition of miR­92a­3p promoted angiogenesis in vitro and in vivo. miR­92a­3p overexpression blocked the pro­angiogenic effects of Exo-H2O2 on target ECs. Tissue factor (TF), a molecule involved in angiogenesis, was increased in HUVECs in which miR­92a­3p expression was downregulated, as shown by mRNA sequencing. TF was also predicted as a target of miR­92a­3p by using the RNAhybrid program. The overexpression or suppression of miR­92a­3p modified TF expression at both the mRNA and protein level, as measured by RT­qPCR and western blot analysis, respectively. Luciferase reporter assays suggested that miR­92a­3p inhibited TF expression by binding to the 3' untranslated region of TF. On the whole, the findings of the present study demonstrate that exosomes released from oxidative stress­activated ECs stimulate angiogenesis by inhibiting miR­92a­3p expression in recipient ECs, and TF may be involved in the regulatory effects of miR­92a­3p on angiogenesis.