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Background: Extracellular volume (ECV) overload and endothelial cell dysfunction are mortality risk factors in hemodialysis (HD) patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in HD patients. We hypothesized there would be associations between ET-1 and ECV overload in hypertensive HD patients., Methods: We obtained pre-HD ET-1, ECV/weight (bioimpedance spectroscopy), pre-HD hemodynamics, and ambulatory blood pressure (BP) in an HD cohort. Following appropriate transformations, we conducted correlation and linear regression analyses idendifying associations between ET-1, ECV overload, total peripheral resistance index (TPRI), cardiac index (CI), and ambulatory BP., Results: Among 66 patients, median ET-1 was 1.93 (1.49-2.56) pg/ml. Median pre-HD ECV/weight, median TPRI, mean CI, and mean systolic ambulatory BP were 0.25 (0.22-0.30) l/kg, 3,161 (2,711-3,642) dynes × s/cm-5/m2, 2.92 (0.6) l/min/m2, and 143 (14) mm Hg, respectively. After reciprocal-transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r = 0.3, P = 0.01), log-transformed TPRI (r = -0.3, P = 0.006), CI (r = 0.3, P = 0.009), and ambulatory BP (r = -0.3, P = 0.02). These associations persisted in linear regression analysis (β = 0.15, P = 0.002; β = -0.8, P = 0.002; β = 0.2, P = 0.002; β = -19, P = 0.03)., Conclusions: In hypertensive HD patients, ET-1 associates with ECV overload higher TPRI and ambulatory BP, and lower CI. Further research is necessary to determine if ECV reduction lowers ET-1 or if pharmacologic ET-1 antagonism can improve outcomes in HD patients with refractory ECV overload., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cigarette smoking is believed to accelerate age-related neurodegeneration. Despite significant sex differences in both smoking behaviors and brain structures, the active literature is equivocal in parsing out a sex difference in smoking-associated brain structural changes., Objective: The current study examined subcortical and lateral ventricle gray matter (GM) volume differences among smokers, active, past, and never-smokers, stratified by sex., Methods: The current study data included 1959 Dallas Heart Study (DHS) participants with valid brain imaging data. Stratified by gender, multiple-group comparisons of three cigarette-smoking groups were conducted to test whether there is any cigarette-smoking group differences in GM volumes of the selected regions of interest (ROIs)., Results: The largest subcortical GM volumetric loss and enlargement of the lateral ventricle were observed among past smokers for both females and males. However, these observed group differences in GM volumetric changes were statistically significant only among males after adjusting for age and intracranial volumes., Conclusions: The study findings suggest a sex difference in lifetime-smoking-associated GM volumetric changes, even after controlling for aging and intracranial volumes.

Subjective wellbeing may predict future health conditions, and lower self-rated physical health (SRH) is associated with the presence of chronic conditions, such as cardiovascular disease (CVD). This study examines whether subjective wellbeing and SRH predict long-term CVD conditions for women using the Midlife in the United States study. The study cohort includes 1716 women participants who completed waves 1 (1995-1996), 2 (2004-2006), and 3 (2013-2014). Data on demographics, chronic conditions of diabetes and CVD, subjective wellbeing (life satisfaction, positive affect, and negative affect), and SRH were collected repeatedly at each wave. Multiple logistic regressions were conducted to test whether subjective wellbeing was associated with a lifetime CVD risk. Greater life satisfaction was significantly associated with a lower risk of CVD at 10 years (odds ratio (OR): 0.83; 95% confidence interval (CI): 0.74-0.95) and 19 years (OR: 0.83; 95% CI: 0.74-0.93), while positive and negative affects were not significantly associated. Additionally, better physical SRH significantly lowered odds of having cardiovascular conditions at both 10 years (OR: 0.79; 95% CI 0.68-0.92) and 19 years (OR 0.74; 95% CI: 0.64-0.86). Measures of life satisfaction and SRH can be used as additional CVD screening tools.

Objective: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions Trial found no benefit of renal artery stenting (RAS) over medical therapy, although it was underpowered to detect a benefit among patients with chronic kidney disease (CKD). A post hoc analysis demonstrated improved event-free survival after RAS for patients whose renal function improved by 20% or more. A significant obstacle to achieving this benefit is the inability to predict which patients' renal function will improve from RAS. The objectives of the current study were to identify predictors of renal function response to RAS., Methods: The Veteran Affairs Corporate Data Warehouse was queried for patients who underwent RAS between 2000 and 2021. The primary outcome was improvement in renal function (estimated glomerular filtration rate [eGFR]) after stenting. Patients were categorized as responders if the eGFR at 30 days or greater after stenting increased by 20% or more compared with before stenting. All others were nonresponders., Results: The study cohort included 695 patients with a median follow-up of 7.1 years (interquartile range, 3.7-11.6 years). Based on postoperative change in eGFR, 202 stented patients (29.1%) were responders, and the remainder (n = 493 [70.9%]) were nonresponders. Before RAS, responders had a significantly higher mean serum creatinine, lower mean eGFR, and higher rate of decline of preoperative GFR in the months before stenting. After stenting, responders had a 26.1% increase in eGFR, compared with before stenting (P < .0001), which remained stable during follow-up. In contrast, nonresponders had a progressive 5.5% decrease in eGFR after stenting. Logistic regression analysis identified three predictors of renal function response to stenting: (1) diabetes (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.44-0.91; P = .013), (2) CKD stages 3b or 4 (OR, 1.80; 95% CI, 1.26-2.57; P = .001), and (3) rate of decline in preoperative eGFR per week before stenting (OR, 1.21; 95% CI, 1.05-1.39; P = .008). CKD stages 3b and 4 and the rate of decline in preoperative eGFR are positive predictors of renal function response to stenting, whereas diabetes is a negative predictor., Conclusions: Based on our data, patients in CKD stages 3b and 4 (eGFR 15-44 mL/min/1.73 m 2 ) are the only subgroups with a significant probability of improved renal function after RAS. The rate of decline of preoperative eGFR over the months before stenting is a powerful discriminator of patients who are most likely to benefit from RAS. Specifically, patients with a more rapid decrease in eGFR before stenting have a significantly greater probability of improved renal function with RAS. In contrast, diabetes is a negative predictor of improved renal function, so interventionalists should be circumspect about RAS in diabetic patients., (Published by Elsevier Inc.)

Objective: To compare short- and mid-term outcomes of patients with femoropopliteal (FP) occlusive disease treated with a retrograde vs antegrade crossing strategy., Background: Few studies have directly compared procedural details and outcomes after retrograde vs antegrade crossing of FP lesions., Methods: Patients undergoing retrograde approaches to FP lesions were identified from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry between 2007 and 2015. These patients were matched 1:1 to patients treated with antegrade crossing strategies based on age, gender, comorbidities, indication for procedure, and lesion characteristics. Technical success, major adverse limb events (MALEs), and overall device cost were compared between retrograde and antegrade-only crossing., Results: A total of 116 patients (58 antegrade and 58 retrograde) were included. The retrograde group had higher prevalence of coronary artery disease and presence of chronic total occlusions. The retrograde approach was associated with significantly longer procedural time (186 ± 70 minutes vs 124.4 ± 60 minutes; P<.001), but similar technical success (91.4% vs 96.6%; P=.24). There was no significant difference in perioperative morbidity. Patients treated with a retrograde approach had a lower total amputation rate (8.6% vs 22.4%; P=.04) and no difference in overall mortality (8.6% vs 5.2%; P=.47). Mean procedural costs were similar in the antegrade and retrograde groups., Conclusion: In patients with similar disease characteristics, a retrograde approach to FP occlusive disease was associated with longer procedural time, but improved limb salvage, without significant difference in procedural cost.

Background: Hyperphosphatemia occurs frequently in end-stage renal disease patients on hemodialysis and is associated with increased mortality. Hyperphosphatemia contributes to vascular calcification in these patients, but there is emerging evidence that it is also associated with endothelial cell dysfunction., Methods: We conducted a cross-sectional study in hypertensive hemodialysis patients. We obtained pre-hemodialysis measurements of total peripheral resistance index (TPRI, non-invasive cardiac output monitor) and plasma levels of endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA). We ascertained the routine peridialytic blood pressure (BP) measurements from that treatment and the most recent pre-hemodialysis serum phosphate levels. We used generalized linear regression analyses to determine independent associations between serum phosphate with BP, TPRI, ET-1, and ADMA while controlling for demographic variables, parathyroid hormone (PTH), and interdialytic weight gain., Results: There were 54 patients analyzed. Mean pre-HD supine and seated systolic and diastolic BP were 164 (27), 158 (21), 91.5 (17), and 86.1 (16) mmHg. Mean serum phosphate was 5.89 (1.8) mg/dL. There were significant correlations between phosphate with all pre-hemodialysis BP measurements (r = 0.3, p = .04; r = 0.4, p = .002; r = 0.5, p < .0001; and r = 0.5, p = .0003.) The correlations with phosphate and TPRI, ET-1, and ADMA were 0.3 (p = .01), 0.4 (p = .007), and 0.3 (p = .04). In our final linear regression analyses controlling for baseline characteristics, PTH, and interdialytic weight gain, independent associations between phosphate with pre-hemodialysis diastolic BP, TPRI, and ET-1 were retained (β = 4.33, p = .0002; log transformed β = 0.05, p = .005; reciprocal transformed β = -0.03, p = .047)., Conclusions: Serum phosphate concentration is independently associated with higher pre-HD BP, vasoconstriction, and markers of endothelial cell dysfunction. These findings demonstrate an additional negative impact of hyperphosphatemia on cardiovascular health beyond vascular calcification., Trial Registration: The study was part of a registered clinical trial, NCT01862497 (May 24, 2013)., (© 2022. The Author(s).)

Purpose: There is lack of uniformity regarding the ideal insertional torque with which dental implants need to be placed. The purpose of this retrospective analysis is to compare the incidence of early dental implant failures with an insertional torque less than 30 N-cm to implants placed with an insertional torque 30 N-cm or greater., Methods: A retrospective cohort study was conducted to evaluate dental implants placed between 2015 and 2016 at the Veterans Affairs North Texas Health Care System in Dallas. The primary predictor variable was dental implant insertional torque, measured at the time of implant placement as either greater than or equal to 30 N-cm or less than 30 N-cm. The primary outcome variable was early implant failure, defined as implant exfoliation noted by the patient or failure due to implant movement or pain necessitating explantation before prosthesis loading. The study conducted a time-to-event analysis to examine a group difference in time to implant failure between insertional torque group greater than or equal to 30 N-cm and less than 30 N-cm using Kaplan-Meir curves and a frailty model. The time to follow-up was censored at 6 months., Results: One hundred three patients had 214 implants placed, with early failures occurring in 14 implants (6.5%). Implants placed with an insertional torque less than 30 N-cm were nearly 14 times more likely to have an early failure compared to implants placed with an insertional torque 30 N-cm or greater (hazard ratio = 13.909; 95% confidence interval, 1.835 to 105.416), which was statistically significant (P = .0108)., Conclusions: The results of this retrospective cohort study suggest that insertional torque values less than 30 N-cm are associated with early dental implant failures. Future, prospective studies will be performed to further elucidate the association between insertional torque and early dental implant failure., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. All rights reserved.)

Background/objective: Heart disease is the leading cause of death among women in the United States, and women are experiencing more strokes at younger ages than men. Despite accumulating evidence of increased burden of heart disease among women, there is little data on gender difference in heart disease-related mortality during the COVID-19 pandemic., Method: This study extracted the data of weekly number of deaths between January 2017 and December 2020 from the United States Center for Disease and Control and Prevention (CDC) mortality and morbidity data, modified to a monthly scale. Stratified by gender, the study applied the Farrington method on monthly data to calculate excess number of deaths. Excess heart disease-related deaths were observed in March and July 2020 for both males and females., Results: While the overall number of heart disease-related deaths was higher in men than women among US population < 75 years old, a greater rate increase of heart disease-related deaths in 2020 from 2019 was observed among women than men. This increased burden was more pronounced among young women < 25 years old. A similar pattern of excess deaths caused by underlying heart disease condition was observed for both genders during COVID-19 pandemic. On the other hand, increase in heart disease-related death burden in 2020 from 2019 was greater amongst females than males. This may be partially accounted for by deferred cardiovascular care and prevention amongst women during the pandemic., Conclusions: While no gender difference was observed in excess deaths caused by underlying heart disease condition, females faced a greater increase in heart disease-related death burden during the pandemic compared to pre-pandemic than males., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Introduction: Extracellular volume (ECV) predicts mortality in hemodialysis patients, but it is difficult to assess clinically. Peridialytic blood pressure (BP) measurements can help ECV assessment. Orthostatic BP is routinely measured clinically, but its association with ECV is unknown., Methods: In a cohort of hypertensive hemodialysis patients, we measured posthemodialysis ECV/weight with bioimpedance spectroscopy and analyzed its association with post-HD orthostatic BP measurements obtained during routine care. Using linear and logistic regression, the primary outcomes were orthostatic BP change and orthostatic hypotension (OH) defined by systolic BP decrease of at least 20 mmHg or diastolic decrease of at least 10 mmHg. Model 1 controlled for sex, age, and diabetes. Model 2 additionally controlled for ultrafiltration rate and antihypertensive medications. We conducted sensitivity analysis using OH definition of systolic BP decrease of at least 30 mmHg., Findings: Among 57 participants, mean orthostatic systolic BP change was -7.30 (20) mmHg and mean ECV/weight was 0.24 (0.04) L/kg. Post-HD ECV/weight was not associated with orthostatic systolic BP change (β = 8.2, p = 0.6). There were 16 participants with and 41 participants without OH. The ECV/weight did not differ between these groups (0.22 [0.04] vs. 0.24 [0.05] L/Kg, p = 0.09) and did not predict OH in logistic regression (OR 11, 4.04; 95% CI 0.2-671, 0.03-0.530 in the two models.) In a sensitivity analysis, ECV/weight was lower in the OH group (0.22 [0.03] vs. 0.25 [0.04] L/kg, p = 0.005), but this was accompanied by differences in sex and diabetes. Using logistic regression, there was no independent association between ECV/weight with OH., Discussion: Orthostatic systolic BP change after HD completion is not a reliable indicator of posthemodialysis ECV. When considering other factors associated with orthostatic BP, ECV/weight is not independently associated with OH. Although transient postdialytic differences in intravascular volume may be associated with OH, posthemodialysis OH does not necessarily indicate ECV depletion., (© 2021 International Society for Hemodialysis.)

Hypoplastic left heart syndrome is a congenital anomaly that is uniformly fatal in infancy without immediate treatment. The standard treatment consists of an initial Norwood procedure (stage 1) followed some months later by stage 2 palliation (S2P). The ideal timing of the S2P is uncertain. The Single Ventricle Reconstruction Trial (SVRT) randomized the procedure used in the initial Norwood operation, leaving the timing of the S2P to the discretion of the surgical team. To estimate the causal effect of the timing of S2P, we propose to impute the potential post-S2P survival outcomes using statistical models under the Rubin Causal Model framework. With this approach, it is straightforward to estimate the causal effect of S2P timing on post-S2P survival by directly comparing the imputed potential outcomes. Specifically, we consider a lognormal model and a restricted cubic spline model, evaluating their performance in Monte Carlo studies. When applied to the SVRT data, the models give somewhat different imputed values, but both support the conclusion that the optimal time for the S2P is at 6 months after the Norwood procedure., (© 2021 John Wiley & Sons Ltd.)

Background: Previous studies have suggested that large preoperative AAA size may impact late survival after elective EVAR. It is unclear, however, whether this association applies to patients with smaller AAA between 5.0-5.5 cm, who constitute a substantial portion of patients undergoing elective EVAR. The purpose of this study was to delineate the effect of AAA size between 5.0 and 5.5 cm on mid-term mortality after EVAR by analyzing a large national cohort, the Vascular Quality Initiative (VQI) database., Methods: Using the Vascular Quality Initiative (VQI) national database, patients who underwent EVAR for intact AAA between 2003 and 2018 were identified and stratified based on maximal AAA diameter into 3 groups: Group 1 (4.0 cm ≤ AAA <5.0 cm); Group 2 (5.0 cm ≤ AAA < 5.5 cm); and Group 3 (AAA ≥ 5.5 cm). Cox proportional hazard model and propensity score matching method were used to estimate AAA size effect on all-cause mortality at 1, 3, and 5 years after EVAR while adjusting for potential confounders., Results: The study included 32,398 patients, of whom 81% were men with a mean age of 74. The most common group who underwent EVAR was Group 2 (5.0 cm ≤ AAA < 5.5 cm). Larger AAA size was associated with male sex (75% versus 79% versus 84%, for Groups 1, 2, and 3 respectively; P < 0.0001) and with coronary artery disease (27% versus 29% versus 31%, for Groups 1, 2, and 3 respectively, P< 0.0001); but was negatively associated with active smoking (33% versus 31% versus 30%, for Groups 1, 2, and 3, respectively, P< 0.001). While 10% of the largest and smallest AAA groups (Groups 3 and 1, respectively) were symptomatic, only 5% of patients in Group 2 were symptomatic (P < 0.01). Adjusted Cox proportional hazard modeling revealed that patients in Group 2 were at significantly lower risk of 5-year mortality when compared to patients in Group 3 (HR 0.66, 95% CI 0.61-0.72, P< 0.01), while similar in risk when compared to patients in Group 1 (HR 1.11, 95% CI 0.93-1.32, P= 0.26)., Conclusion: Our analysis found that over 40% of EVAR in the national VQI cohort were performed for AAA < 5.5 cm, with the greatest number of patients undergoing EVAR at AAA size 5.0-5.5cm. Patients with AAA size 5.0-5.5 cm had better 5-year survival outcomes than patients with AAA ≥ 5.5 cm, and similar survival to patients with small AAA between 4.0-5.0 cm., (Published by Elsevier Inc.)

Objective: The optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current recommendations are based on extrapolation of data from trials in coronary artery disease and stroke., Methods: We identified all patients undergoing an elective lower extremity revascularization for CLTI in the Vascular Quality Initiative registry discharged on a mono antiplatelet agent (MAPT) or dual antiplatelet therapy (DAPT)., Results: From 2003 to 2018, 50,890 patients underwent revascularization procedures for CLTI, and were discharged on MAPT or DAPT. Of these, 33,781 patients underwent endovascular therapy (EVT), and 17,109 patients underwent open surgery (OS) procedures. The rate of major amputation at 30 days in the target limb in the EVT group was 0.3% and 0.4% in the OS group (P = .22). On Kaplan-Meier analyses, patients on MAPT at discharge had a higher risk of 1-year major amputation compared with DAPT after EVT but not after OS procedures. Patients on MAPT had lower overall survival and amputation-free survival at 30 days and 1 year compared with DAPT after both EVT and OS. At 1 year, the MAPT group was at higher risk for target lesion reintervention after EVT compared with the DAPT group (15.9% vs 13%; P = .0012). There was no significant difference in thrombosis at 1 year between the MAPT and DAPT groups either after EVT (3.9% vs 3.7%; P = .3048) or OS (3.1% vs 3.2%; P = .2893). On Cox regression analysis, DAPT was associated with improved survival but not major amputation after both EVT and OS., Conclusions: In patients with CLTI, DAPT at the time of discharge has a positive impact on amputation-free survival and overall survival after both EVT and OS as well as target lesion reintervention after EVT. DAPT was not associated with a positive impact on major amputation after either EVT or OS., (Published by Elsevier Inc.)

The current study assessed performance of the new Veterans Affairs (VA) women cardiovascular disease (CVD) risk score in predicting women veterans' 60-day CVD event risk using VA COVID-19 shared cohort data. The study data included 17,264 women veterans-9658 White, 6088 African American, and 1518 Hispanic women veterans-ever treated at US VA hospitals and clinics between 24 February and 25 November 2020. The VA women CVD risk score discriminated patients with CVD events at 60 days from those without CVD events with accuracy (area under the curve) of 78%, 50%, and 83% for White, African American, and Hispanic women veterans, respectively. The VA women CVD risk score itself showed good accuracy in predicting CVD events at 60 days for White and Hispanic women veterans, while it performed poorly for African American women veterans. The future studies are needed to identify non-traditional factors and biomarkers associated with increased CVD risk specific to African American women and incorporate them to the CVD risk assessment.

COVID-19, caused by SARS-CoV-2, is a contagious life-threatening viral disease that has killed more than three million people worldwide to date. Attempts have been made to identify biomarker(s) to stratify disease severity and improve treatment and resource allocation. Patients with SARS-COV-2 infection manifest with a higher inflammatory response and platelet hyperreactivity; this raises the question of the role of thrombopoiesis in COVID-19 infection. Immature platelet fraction (IPF, %) and immature platelet counts (IPC, ×10 9 /l) can be used to assess thrombopoiesis. This study investigates whether the level of thrombopoiesis correlates with COVID-19 severity. A large cohort of 678 well-characterized COVID-19 patients was analyzed, including 658 (97%) hospitalized and 139 (21%) admitted to the intensive care unit (ICU). Elevated percentage IPF at presentation was predictive of length of hospitalization (P < 0·01) and ICU admission (P < 0·05). Additionally, percentage IPF at the peak was significantly higher among ICU patients than non-ICU patients (6·9 ± 5·1 vs 5·3 ± 8·4, P < 0·01) and among deceased patients than recovered patients (7·9 ± 6·3 vs 5·4 ± 7·8, P < 0·01). Furthermore, IPC at the peak was significantly higher among ICU patients than non-ICU patients (18·5 ± 16·2 vs. 13·2 ± 8·3, P < 0·05) and among patients on a ventilator than those not (22·1 ± 20·1 vs.13·4 ± 8·4, P < 0·05). Our study demonstrated that elevated initial and peak values of percentage IPF and IPC might serve as prognostic biomarkers for COVID-19 progression to severe conditions., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Infants with hypoplastic left heart syndrome require an initial Norwood operation, followed some months later by a stage 2 palliation (S2P). The timing of S2P is critical for the operation's success and the infant's survival, but the optimal timing, if one exists, is unknown. We attempt to identify the optimal timing of S2P by analyzing data from the Single Ventricle Reconstruction Trial (SVRT), which randomized patients between two different types of Norwood procedure. In the SVRT, the timing of the S2P was chosen by the medical team; thus with respect to this exposure, the trial constitutes an observational study, and the analysis must adjust for potential confounding. To accomplish this, we propose an extended propensity score analysis that describes the time to surgery as a function of confounders in a discrete competing-risk model. We then apply inverse probability weighting to estimate a spline hazard model for predicting survival from the time of S2P. Our analysis suggests that S2P conducted at 6 months after the Norwood gives the patient the best post-S2P survival. Thus, we place the optimal time slightly later than a previous analysis in the medical literature that did not account for competing risks of death and heart transplantation., (© 2020 The International Biometric Society.)

The Suicide Cognitions Scale (SCS) assesses suicide-specific cognitions which may drive suicide risk. Nonetheless, prior work has been mixed regarding optimal factor structure. Additionally, this measure has not been validated for use with veterans with military sexual trauma-related posttraumatic stress disorder (MST-related PTSD), a population that is at elevated risk for suicidal self-directed violence (SDV). This study sought to determine the optimal factor structure of the SCS for use with veterans with MST-related PTSD as well as its psychometric properties. An exploratory factor analysis revealed a four-factor structure, including unlovability, unbearability, unsolvability, and negative urgency. The SCS also demonstrated excellent internal consistency and good convergent validity. This study identified a novel factor, negative urgency, which may explain some of the predictive power of the SCS found in previous research. This paper provides initial support for a four-factor structure of the SCS among those with MST-related PTSD. Additional work remains necessary in evaluating the SCS as a tool for detecting risk for future suicidal SDV among veterans with MST-related PTSD.

The burden of COVID-19 has been noted to be disproportionately greater in minority women, a population that is nevertheless still understudied in COVID-19 research. We conducted an observational study to examine COVID-19-associated mortality and cardiovascular disease outcomes after testing (henceforth index) among a racially diverse adult women veteran population. We assembled a retrospective cohort from a Veterans Affairs (VA) national COVID-19 shared data repository, collected between February and August 2020. A case was defined as a woman veteran who tested positive for SARS-COV-2, and a control as a woman veteran who tested negative. We used Kaplan-Meier curves and the Cox proportional hazards model to examine the distribution of time to death and the effects of baseline predictors on mortality risk. We used generalized linear models to examine 60-day cardiovascular disease outcomes. Covariates studied included age, body mass index (BMI), and active smoking status at index, and pre-existing conditions of diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and a history of treatment with antiplatelet or anti-thrombotic drug at any time in the 2 years prior to the index date. Women veterans who tested positive for SARS-CoV-2 had 4 times higher mortality risk than women veterans who tested negative (Hazard Ratio 3.8, 95% Confidence Interval CI 2.92 to 4.89) but had lower risk of cardiovascular events (Odds Ratio OR 0.78, 95% CI 0.66 to 0.92) and developing new heart disease conditions within 60 days (OR 0.67, 95% CI 0.58 to 0.77). Older age, obesity (BMI > 30), and prior CVD and COPD conditions were positively associated with increased mortality in 60 days. Despite a higher infection rate among minority women veterans, there was no significant race difference in mortality, cardiovascular events, or onset of heart disease. SARS-CoV-2 infection increased short-term mortality risk among women veterans similarly across race groups. However, there was no evidence of increased cardiovascular disease incidence in 60 days. A longer follow-up of women veterans who tested positive is warranted.

Background The current American College of Cardiology/American Heart Association women cardiovascular disease (CVD) risk score suboptimally estimates CVD risk for young and minority women in the military. The current study developed an internally validated CVD risk score for women military service members and veterans using the Veterans Affairs (VA) national electronic health records data. Methods and Results The study cohort included 69 574 White, Black, and Hispanic women service members and veterans aged 30 to 79 years in 2007 treated in the VA Health Care System between January 1, 2007 and December 31, 2017 (henceforth, VA women). Stratified by race and ethnicity, the new VA women CVD risk model estimated risk coefficients and 10-year CVD risk using a time-variant covariate Cox model. Harrell C-statistics, calibration plots, and net classification index were used to assess accuracy and prognostic performance of the new VA women CVD risk model. The new internally validated VA women CVD risk score performed better in predicting VA women 10-year atherosclerosis cardiovascular disease risk than the pooled cohort American College of Cardiology/American Heart Association risk score in both accuracy (White Harrell C-statistics, 70% versus 61%; Black, 68% versus 63%) and prognostic performance (White net classification index, 0.31; 95% CI, 0.26-0.33; Black net classification index, 0.06; 95% CI, 0.03-0.09). Conclusions The proposed VA women CVD risk score improves accuracy of the existing American College of Cardiology/American Heart Association CVD risk assessment tool in predicting long-term CVD risk for VA women, particularly in young and racial/ethnic minority women.

Background: Endovascular therapy is often the preferred first treatment option for chronic limb threatening ischemia (CLTI) patients. Drug coated balloons (DCB) reduce restenosis rates compared to percutaneous transluminal angioplasty (PTA), however DCB use has not been studied systematically in patients with CLTI. Thus, the optimal treatment option for these complex lesions remains controversial., Methods: We report on 327 patients with CLTI treated either with DCB (n = 105) or non-DCB (n = 222) for femoropopliteal disease. Data were retrieved from the Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851). Two DCB types were used at the discretion of the operator: Lutonix® (BARD Peripheral Vascular, Inc., Tempe, AZ, USA) and IN.PACT AdmiralTM (Medtronic, Santa Rosa, CA, USA). Odds ratios and the respective 95% confidence interval were synthesized to examine the association between the two groups in terms of all-cause mortality, target limb repeat endovascular or surgical revascularization, target vessel revascularization (TVR), major and minor amputation at 12 months of follow up., Results: The mean lesion length was 150.0 mm (SD:123.2) and 151.2 mm (SD:108.3) for the DCB and non-DCB group respectively. No difference between the two groups was detected in terms of all-cause mortality (2.86%vs2.7%,p = .94), target limb repeat endovascular or surgical revascularization (16.19%vs12.61%,p = .25), TVR (16.19%vs.11.71%,p = .26) or minor amputation (15.24%vs10.81%,p = .25) at 12 months of follow up. Although a higher incidence of 12 months major amputation was observed in the DCB group (11%vs.4%,p = .01), after adjusting for several risk factors the odds of major amputation were not statistically different between the DCB and non-DCB groups (OR:1.54;95%CI:0.53-4.51;p = .43)., Conclusions: Both DCB and non-DCB strategies are effective modalities for revascularization of patients with CLTI. No differences were identified between the DCB and non-DCB group in terms of late outcomes during 12 months of follow up., Competing Interests: Declaration of competing interest Dr. Banerjee reports honoraria from Medtronic, Gore, Astra Zeneca, Janssen; research grants (institutional) from Boston Scientific, Abbott Vascular, Merck; Board of Directors for the Cardiovascular Innovations Foundation. Dr. Armstrong is a consultant to Abbott Vascular, Boston Scientific, Cardiovascular Systems Incorporated (CSI), Medtronic, Philips, and PQ Bypass. All other authors have no relationships to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Background Atherosclerotic cardiovascular disease (ASCVD) is the third leading cause of death in women service members and veterans. This study assessed 10-year ASCVD risk in women service members and veterans using their own electronic health record data extracted from Veterans Affairs (VA) national Corporate Data Warehouse database. Methods and Results We retrospectively followed 69 574 VA women, aged 30 to 79 years, from 2007 to 2017. Of these, 52% were whites (n=36 172), 42% were blacks (n=29 232), and 6% were Hispanics (n=4171). Risk factors and ASCVD events (nonfatal myocardial infarction, nonfatal stroke, and cardiac deaths) were identified using diagnostic and procedural codes from electronic health records. Then, within the same construct of the current American College of Cardiology/American Heart Association 10-year ASCVD risk assessment models for women, coefficients for risks factors were recalculated using the VA national electronic health record data, stratified by race (hereafter, VA women model). Our study found a curvilinear association of aging with increased risk of 10-year ASCVD event in VA women starting at ages as young as 30 years across all race groups. The VA women model performance in predicting ASCVD events at 10 years was mixed-moderate in discrimination (C statistics, 0.61-0.64) but good in accuracy, as demonstrated by calibration plots approximating a 45° line. Conclusions The study finding, a curvilinear association of aging with increased ASCVD risk in VA women across all races, demonstrates the need for cardiovascular risk screening of younger VA women, aged <45 years.

Purpose: To report a propensity score analysis comparing outcomes of the Supera interwoven nitinol stent to bare nitinol stents (BNS) in the femoropopliteal segment. Materials and Methods: A retrospective study was conducted utilizing data extracted from the Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) on 871 patients (mean age 65.1 years; 713 men) who underwent femoropopliteal balloon angioplasty with either Supera stent implantation in 118 limbs or other contemporary BNS in 753 limbs between January 2006 and December 2016. All patients in both groups were matched for baseline demographic and clinical characteristics in a 1:1 propensity score matching using the nearest neighbor method to create the 118-patient matched BNS cohort. One-year outcomes included all-cause mortality, target vessel revascularization (TVR), and target limb revascularization (TLR). An additional core laboratory analysis was conducted to measure the deployed length of Supera stents. Results: In unmatched data, the Supera stent group had a numerically lower rate of TVR (7.6% vs 13.4%, p=0.08) and a significantly lower 1-year TLR rate (7.6% vs 16.2%, p=0.02) compared to the BNS group. Both groups had similar 1-year mortality (2.5% vs 2.7%, p=0.9). Kaplan-Meier analysis demonstrated that the Supera group had a significantly lower risk of TVR (p=0.02) and TLR (p=0.002) than the BNS group. After propensity matching, the 1-year TVR estimate was lower for Supera stents (7.6% vs 12.7%, p=0.08) and significantly lower for TLR (7.6% vs 13.6%, p=0.04) than the BNS group. There was no statistically significant association between Supera stent elongation (>10% of the labeled stent length) and 1-year risk of TLR (p=0.6). Conclusion: Supera stent usage in femoropopliteal intervention was associated with reduced risk of 1-year repeat target limb revascularization compared with BNS treatment in both unmatched and matched cohorts.

Objective: Peripheral artery disease is a common comorbidity in patients with end-stage renal disease (ESRD), but there is a paucity of data comparing outcomes of different interventions in this group of patients. In this study, we examined perioperative outcomes of lower extremity endovascular revascularization (ER) and open revascularization (OR) in dialysis patients with critical limb ischemia (CLI)., Methods: Patients on dialysis and undergoing ER and OR for CLI from 2011 to 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program dataset. Patient demographics, comorbidities, anatomic features, and perioperative outcomes were compared between ER and OR procedures., Results: From 2011 to 2015, 1021 lower extremity revascularizations were performed in dialysis patients with CLI. In this group, 535 were ER (53%) and 486 were OR (47%) procedures. Although demographic characteristics such as age and gender were similar between the two groups, there was a higher proportion of Caucasians and African Americans in the OR group. Patients undergoing open and endovascular procedures had similar rates of hypertension, congestive heart failure, diabetes, chronic obstructive pulmonary disease, and bleeding disorders. A minority of procedures (4%) were emergencies, which were distributed equally between the two groups. Preoperative aspirin usage was higher in the ER group (84% vs 78%; P = .024), beta-blocker use was higher in the OR group (79% vs 74%; P = .08), and statin use was similar between the two groups (72% in OR and 70% in ER; P = .54). On risk-adjusted multivariate analysis, OR was associated with a lower rate of major amputation (5.97% vs 11.78%; odds ratio, 0.48; 95% confidence interval [CI], 0.26-0.85), but a higher rate of postoperative bleeding (29.6% vs 8.97%; odds ratio, 2.86; 95% CI, 1.8-4.35) and wound complications (15% vs 3%; odds ratio, 4.5; 95% CI, 2.38-8.3). The 30-day mortality and cardiovascular morbidity were similar between the two groups., Conclusions: In patients with ESRD with CLI, OR is associated with a lower risk of major limb amputation but a higher rate of postoperative wound complications and bleeding, compared with ER. Cardiovascular complications, 30-day mortality, reinterventions and readmissions were similar between the two groups. In patients with ESRD with CLI, OR should be considered as an option for limb salvage if feasible. Long-term outcomes comparing the two types of procedures are needed., (Published by Elsevier Inc.)

Purpose: To investigate the effect of abdominal aortic aneurysm (AAA) size on mid- and long-term survival after endovascular aneurysm repair (EVAR)., Materials and Methods: Retrospective data were collected from 325 consecutive patients (mean age 69.7 ± 8.5 years; 323 men) who underwent EVAR for intact AAA at a single institution between January 2003 and December 2013. The primary endpoint was death at 3, 5, and 10 years after EVAR. Optimal cutoff points for AAA size and age were determined using receiver operating characteristics (ROC) curves. Time to event analyses (Kaplan-Meier curves and Cox proportional hazard models) were employed to determine any differences in all-cause mortality outcomes between AAA size groups. Cox models were adjusted for age and other comorbidities (hypertension, hyperlipidemia, coronary artery disease, smoking status, symptomatic status, and creatinine); the outcomes are reported as the hazard ratio (HR) with 95% confidence interval (CI)., Results: The cohort was dichotomized according to the ROC analysis, which defined an optimal cutoff point of 5.6 cm for AAA size and >70 years for age. The mean follow-up period post EVAR was 45.5±29.2 months. In total, 134 (41.2%) patients died during the 10-year follow-up. Thirty-day mortality was 1.1% (2/184) in the patients with AAA <5.6 cm and 2.1% (3/141) in patients with AAA ≥5.6 cm (p=0.45). All-cause mortality was not significantly affected by comorbidities. However, AAA size ≥5.6 cm was associated with increased 3-year mortality risk (HR 1.59, 95% CI 1.001 to 2.52, p<0.049) but not 5-year (HR 1.44, 95% CI 0.98 to 2.10, p=0.062) or 10-year mortality (HR 1.28, 95% CI 0.91 to 1.80, p=0.149). After adjusting for comorbidities, AAA size ≥5.6 cm was no longer significantly associated with morality at any time point. Using a larger size cutoff (AAA size ≥6.0 cm) resulted in improved statistical significance in the unadjusted model. In the adjusted Cox model, AAA size ≥6.0 cm was significantly associated with increased risk of mortality at 3 years (HR 1.67, 95% CI 1.01 to 2.77, p<0.047), but not at longer time points., Conclusion: Our study demonstrates that midterm survival after EVAR is significantly and independently associated with AAA size even after correcting for comorbidities. However, in the long term, preoperative AAA size is not an independent predictor of mortality.

Background: Use of atherectomy for the treatment of peripheral arterial disease (PAD) is increasing as an adjunctive treatment to either conventional or drug-coated balloon angioplasty. There is limited data on atherectomy outcomes in below-the-knee (BTK) endovascular interventions., Methods: Data from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851) were analyzed to examine predictors of atherectomy use and its associated 1-year patency rate. We analyzed 518 BTK procedures performed between January 2005 and December 2016., Results: Overall a total of 518 BTK procedures were treated in 430 patients, and 43% of interventions used atherectomy. African American patients were less likely (13% vs 25%; |standard residual| = 3.41) to be treated with atherectomy. Use of atherectomy was lower in chronic total occlusive (CTO) lesions (48% vs 58%; P = 0.02). There were no significant associations of baseline comorbidities, critical limb ischemia (CLI), ankle-brachial index, number of BTK vessel run-off, or vessel location with atherectomy use. Compared with patients without atherectomy, use of atherectomy was associated with lower incidence of repeat target limb intervention at 1 year after adjusting for age, CLI, in-stent restenosis, heavy calcification, presence of diffuse disease, and CTO lesion traits (Hazard Ratio 0.41, 95% confidence interval 0.23-0.72; P < 0.01)., Conclusions: Compared with no atherectomy, use of atherectomy in BTK interventions is associated with lower rates of 1-year repeat target limb revascularization. These findings require confirmation in prospective, randomized clinical studies., (© 2018 Wiley Periodicals, Inc.)

Background: The contemporary limb outcomes and costs of stent-based vs non-stent based strategies in endovascular revascularization of femoropopliteal (FP) peripheral artery disease (PAD) are not well understood., Methods and Results: We present data from the ongoing United States multicenter Excellence in Peripheral Artery Disease Registry between 2006-2016 to compare stent vs non-stent treatment outcomes and associated costs in FP interventions. A total of 2910 FP interventions were performed in 2162 patients (mean age, 66 years), comprising 1339 stent based (superficial femoral artery, 93%) in 1007 patients and 1571 non-stent interventions (superficial femoral artery, 85%) in 1155 patients. A growing trend for non-stent based interventions and a declining trend in repeat revascularization rate at 1 year were observed across years of registry enrollment. Stent implantation was the prevailing strategy in treating longer FP lesions (mean length, 152 mm vs 105 mm; P<.001) and chronic total occlusions (65% vs 40%; P<.001), while stent implantation was employed less frequently when treating in-stent restenotic lesions (14% vs 20%; P<.001). Stent and non-stent interventions had similar 1-year limb outcomes in all-cause death, target-limb revascularization, target-vessel revascularization, and major or minor amputation. The average procedure costs for the stent group were significantly higher than the non-stent group ($6215 vs $4790; P<.001)., Conclusion: There is a growing trend for non-stent FP artery interventions, with a significant decline in 1-year target-limb revascularization rates over time. One-year limb outcomes in stent-based compared to non-stent interventions are similar; however, at a significantly higher procedural cost.

Background: Although long-term durability and improved perioperative outcome of endovascular abdominal aortic aneurysm (AAA) repair has been demonstrated, some studies have suggested an increased rate of secondary interventions compared with open AAA repair. More recent data suggest that rates between the two modalities may be similar. We investigated the rate of secondary intervention in patients undergoing endovascular aortic aneurysm repair (EVAR) or open AAA repair for intact AAA and the effect of secondary intervention on long-term mortality in these two groups of patients., Methods: A retrospective, single-institution review was conducted between January 2003 and December 2012. Secondary intervention was defined as any intervention within 30 d of the procedure or an AAA repair-related procedure after 30 d, which included repair of endoleaks and incisional hernia repair. Group differences in demographic and baseline characteristics were examined using Cochran-Mantel-Haenszel and Wilcoxon rank sum tests for categorical and continuous variables, respectively., Results: A total of 342 patients underwent operative repair of intact AAA. Two hundred seventy four patients underwent EVAR and 68 patients underwent open AAA repair. The mean age overall was 68.6 y and was not significantly different between the two repair groups. The overall rate of secondary intervention was significantly lower in the EVAR group compared with the open AAA repair group (11% versus 27%, P = 0.001). In the EVAR group, 30 patients underwent 37 secondary interventions. In the open repair group, 18 patients underwent 20 reinterventions. The most common secondary intervention was repair of type 2 endoleak (n = 13, 4.7% of patients) after EVAR and incisional hernia repair (n = 4, 5.9% of patients) after open AAA repair. Most secondary interventions (15/20) after open AAA repair occurred within 30 d, whereas most secondary intervention (33/37) after EVAR occurred after 30 d. Comparison of late (>30 d) reintervention between the two groups revealed a significantly lower rate of secondary intervention after open AAA repair (27.8% of all reinterventions after open versus 86.7% of all reinterventions after EVAR, P < 0.001). The overall 10-y mortality rate was 39.1%, and not statistically different between the two repair groups. Estimated survival analysis demonstrated no significant effect of secondary intervention on mortality after EVAR (logrank P = 0.45). Secondary intervention after open repair did not significantly affect long-term survival (logrank P = 0.05)., Conclusions: This study highlights the dramatic change in practice pattern in AAA repair over time. In this study, patients treated with EVAR had a significantly lower overall rate of secondary intervention compared with patients treated with open AAA repair. This was likely secondary to increased perioperative morbidity and mortality and a bias toward more complex patients in the open repair group. In the long term, however, there were significantly fewer reinterventions after open AAA repair. Secondary interventions did not affect long-term survival after EVAR., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Paclitaxel drug-eluting stents (DESs) have been shown to improve primary patency of femoropopliteal lesions compared to plain balloon angioplasty with provisional bare-metal stents (BMSs) in randomized controlled studies. However, data are lacking on patency outcomes of real-world DES use relative to BMS use. This study compared clinically driven target-lesion revascularization (TLR), target-vessel revascularization (TVR), and target-limb revascularization outcomes at 1 year between DES and BMS treatments in a real-world setting., Methods: The study identified 174 DES (Zilver PTX; Cook Medical) and 784 BMS femoropopliteal interventions from the available 969 Excellence in Peripheral Artery Disease (XLPAD) registry patients between October 2013 and December 2016. We analyzed both unmatched (174 DES and 784 BMS) and propensity score (PS)-matched datasets (174 for each)., Results: This study found that patients who underwent DES femoropopliteal endovascular revascularization had significantly lower TLR rates in both unmatched (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.35-0.91; P=.02) and matched data (HR, 0.50 95% CI, 0.27-0.91; P=.02). The DES group had a 43% lower TVR risk than the BMS group in the PS matched cohort (HR, 0.57; 95% CI, 0.33-0.98; P=.04). Mortality rate in the DES group (5%) was significantly higher than the BMS group in both unmatched (2%; P=.04) and matched groups (1%; P=.046) at 1 year., Conclusions: Patients treated with DES had higher lesion and vessel patency than BMS after adjusting for confounding, which included complexity of lesion characteristics and operators' clinical decision-making regarding selection of treatment modalities, in femoropopliteal endovascular interventions in a real-world registry.

With growing use of drug-coated balloons (DCB) for femoropopliteal (FP) artery interventions, there is limited information on rates of real-world adjunctive stent use and its association with short and long-term outcomes. We report on 225 DCB treated FP lesions in 224 patients from the Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851) between 2014 and 2016. Cochran-Mantel-Haenszel and Wilcoxon rank sum statistics were used to compare stented (planned or 'bail-out') versus non-stented DCB treated lesions. Stents were implanted in 31% of FP DCB interventions. Among the 70 stents implanted, 46% were for 'bail-out' indications and 54% were planned. Lesions treated with stents were longer (mean 150 mm vs 100 mm; p < 0.001) and less likely to be in-stent restenosis lesions (10% vs 28%; p=0.003). Stenting was significantly more frequent in complex FP lesions, including chronic total occlusions (66% vs 34%; p < 0.001). For bail-out stenting, interwoven nitinol stents were the most common type (50%) followed by drug-eluting stents (34%) and bare-metal stents (22%). There were no differences in peri-procedural complication rates or 12-month target limb revascularization rates (18.6% vs 11.6%; p=0.162) or 12-month amputation rates (11.4% vs 11%; p=0.92) between lesions where adjunctive stenting was used versus lesions without adjunctive stenting, respectively. In conclusion, in a contemporary 'real-world' adjudicated multicenter US registry, adjunctive stenting was necessary in nearly a third of the lesions, primarily for the treatment of more complex FP lesions, with similar short and intermediate-term clinical outcomes compared with non-stented lesions. ClinicalTrials.gov Identifier: NCT01904851.

Medical students' early clinical encounters may influence their perceptions of geriatrics. This study examines reflective essays written by 3 rd -year medical students on required clinical rotations. Using content analysis, the authors analyzed the essays' thematic content. The authors then used chi-squared analysis to compare themes with geriatric patients (age 60+) to themes with other age groups. One hundred twenty out of 802 essays described a geriatric patient. The most common geriatric themes were (1) death and dying, (2) decision making, (3) meaningful physician-patient interactions, (4) quality of care, and (5) professional development. Geriatric essays were more likely to discuss death/dying and risk-benefit themes and less likely to discuss abuse. Geriatric essays were more likely to describe students' moral distress. Geriatric essays with moral distress were more likely to include empathy themes compared to geriatric essays without moral distress. Geriatric patients may pose unique ethical challenges for early clinical students.

This study compares procedural complications and clinical outcomes between subintimal crossing versus intraluminal crossing during endovascular treatment of infrainguinal peripheral artery chronic total occlusions (CTO). We identified 1335 CTO interventions in 1001 patients from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry from January 2005 to October 2015. Outcomes included 30-day and 12-month all-cause death, non-fatal myocardial infarction or stroke, peripheral artery stent, or vessel, thrombosis (ST), need for any target limb endovascular or surgical revascularization, target limb major amputation and procedural complications. A subintimal crossing technique was necessary in 388 lesions (27% overall in 1335 lesions; 34% ( n=351) in 1023 femoropopliteal lesions, and 12% ( n=37) in 312 infrapopliteal lesions, p<0.01) with a lower procedural ( p<0.01) and technical ( p<0.01) success than the intraluminal in both femoropopliteal and infrapopliteal interventions. There were no significant differences in procedural complications, major adverse cardiac events, or clinically driven target limb revascularization at 1 year between the two groups, except a higher residual dissection rate in the subintimal crossing group than the intraluminal group in femoropopliteal target vessels ( p = 0.04).

Background: The current definitions of psychotic illness lack biological validity, motivating alternative biomarker-driven disease entities. Building on experimental constructs-Biotypes-that were previously developed from cognitive and neurophysiologic measures, we contrast brain anatomy characteristics across Biotypes alongside conventional diagnoses, examining gray matter density (GMD) as an independent validator for the Biotypes., Methods: Whole brain GMD measures were examined in probands, their relatives, and healthy subjects organized by Biotype and then by DSM-IV-TR diagnosis (n = 1409) using voxel-based morphometry with subsequent subject-level regional characterization and distribution analyses., Results: Probands grouped by Biotype versus healthy controls showed a stepwise pattern of GMD reductions as follows: Biotype1, extensive and diffusely distributed GMD loss, with the largest effects in frontal, anterior/middle cingulate cortex, and temporal regions; Biotype2, intermediate and more localized reductions, with the largest effects in insula and frontotemporal regions; and Biotype3, small reductions localized to anterior limbic regions. Relatives showed regionally distinct GMD reductions versus healthy controls, with primarily anterior (frontotemporal) effects in Biotype1; posterior (temporo-parieto-cerebellar) in Biotype2; and normal GMD in Biotype3. Schizophrenia and schizoaffective probands versus healthy controls showed overlapping GMD reductions, with the largest effects in frontotemporal and parietal regions; psychotic bipolar probands had small reductions, primarily in frontal regions. GMD changes in relatives followed regional patterns observed in probands, albeit less extensive. Biotypes showed stronger between-group separation based on GMD than the conventional diagnoses and were the strongest predictor of GMD change., Conclusions: GMD biomarkers depicted unique brain structure characteristics within Biotypes, consistent with their cognitive and sensorimotor profiles, and provided stronger discrimination for biologically driven biotypes than symptom-based diagnoses., (Published by Elsevier Inc.)

Purpose: To determine whether diabetes mellitus has an independent impact on major limb outcomes at 1 year after endovascular treatment of lower extremity peripheral artery disease (PAD)., Methods: The study involved 1906 consecutive patients (mean age 66 years; 1469 men) enrolled in the observational Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) between January 2005 and October 2015 after undergoing index endovascular procedures in 2426 limbs for arterial occlusive disease. Patient outcomes included 12-month target limb amputation (above ankle) and target limb revascularization as well as all-cause death. Kaplan-Meier analysis and adjusted Cox proportional hazard models were used for time-to-event analysis of outcomes for the entire study sample as well as for the critical limb ischemia (CLI) and claudication subgroups. Results of the Cox regression models are reported as the hazard ratio (HR) and 95% confidence interval (CI)., Results: Diabetics undergoing endovascular procedures had higher rates of comorbid conditions (p<0.001), CLI (p<0.001), heavily calcified lesions (p=0.002), multivessel disease (p=0.030), and fewer infrapopliteal runoff vessels (p<0.001). Regression analysis after adjusting for confounders revealed significantly higher target limb major amputation in diabetics compared with nondiabetics (HR 5.02, 95% CI 1.44 to 17.56, p=0.011). However, repeat revascularization rates were similar. When considering CLI and claudication subgroups, diabetes was associated with a nonsignificant increased risk of 12-month major amputation only for patients presenting with CLI (HR 3.48, 95% CI 0.97 to 12.51, p=0.056). Diabetes was also associated with an increased risk of 12-month all-cause mortality in the overall study sample (HR 4.64, 95% CI 2.01 to 10.70, p<0.001) and in the CLI subgroup (HR 14.15, 95% CI 3.16 to 63.32, p<0.001) but not in the claudication subgroup (HR 1.42, 95% CI 0.45 to 4.54, p=0.552)., Conclusion: Diabetes increases the risk of major amputation and all-cause death at 12 months following endovascular revascularization in patients with symptomatic PAD. These risks are especially heightened in patients presenting with CLI.

Paclitaxel-coated drug-coated balloons have significantly improved short-term and mid-term clinical outcomes in patients with symptomatic femoropopliteal peripheral artery disease. However, long-term results are awaited. Furthermore, the clinical success of drug-coated balloons in the infrapopliteal peripheral arteries has been more modest and overall similar to traditional balloon angioplasty, and remains an area of unmet clinical need. This article provides an overview of the clinical evidence for paclitaxel-coated balloons in the femoropopliteal and infrapopliteal peripheral artery distributions and future directions in this area., (Published by Elsevier Inc.)

This study examined a gender difference in 12-month patient outcomes after endovascular intervention for symptomatic peripheral artery disease (PAD) utilizing propensity score-matched Excellence in Peripheral Artery Disease registry data. Mortality and repeat intervention outcomes after endovascular treatment in women compared with men in the existing literature are inconsistent and confounded by other risk factors. The study included 1,084 patients who underwent 1,702 endovascular procedures, at 8 non-Veterans Administration hospitals from January 2005 to October 2015. Frailty hazard ratios by gender for time-to-event analysis were estimated. Women made up about 40% of the study population. After propensity score matching, 449 women and 449 men were included in the analysis, in which women had similar baseline patient and lesion characteristics, laboratory data, procedural characteristics, and medical therapy as men. Within 12-month postintervention, women were at a lower risk of mortality than men (p = 0.05); however, they underwent significantly more frequent repeat revascularization procedures (p = 0.04). In subgroup analysis, women with superficial femoral artery disease were also at higher risk of 12-month repeat intervention than men (p <0.01) and had a higher mortality risk, albeit with an attenuated significance (p = 0.07). Women with PAD are at a higher risk of 12-month repeat intervention than men., (Published by Elsevier Inc.)

Objectives: The aim of this study was to assess actual procedural costs and outcomes comparing wire-catheter and dedicated chronic total occlusion (CTO) device strategies to cross peripheral artery CTOs., Background: Peripheral artery CTO interventions are frequently performed, but there are limited data on actual procedural costs and outcomes comparing wire-catheter and dedicated CTO devices., Methods: The XLPAD (Excellence in Peripheral Artery Disease Intervention) registry (NCT01904851) was accessed to retrospectively compare cost and 30-day and 12-month outcomes of wire-catheter and crossing device strategies for treatment of infrainguinal peripheral artery CTO., Results: Of all 3,234 treated lesions, 42% (n = 1,362) were CTOs in 1,006 unique patients. Wire-catheter approaches were used in 82% of CTOs, whereas dedicated CTO devices were used in 18% (p < 0.0001). CTO crossing device use was associated with significantly higher technical success (74% vs. 65%; p < 0.0001) and mean procedure cost ($7,800.09 vs. $4,973.24; p < 0.0001). Because 12-month repeat revascularization (11.3% vs. 17.2%; p = 0.02) and amputation rates (2.8% vs. 8.5%; p = 0.002) in the CTO crossing device arm were lower compared with the wire-catheter group, the net cost for an initial CTO crossing device strategy was $423.80 per procedure., Conclusions: An initial wire-catheter approach to cross a peripheral artery CTO is most frequently adopted. The use of dedicated CTO crossing devices provides significantly higher technical success and lower reintervention and amputation rates, at a net cost of $423.80 per procedure at 12 months., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Anorexia nervosa (AN) is a severe mental illness characterized by problems with self-perception. Whole-brain neural activations in healthy women, women with AN and women in long-term weight recovery following AN were compared using two functional magnetic resonance imaging tasks probing different aspects of self-perception. The Social Identity-V2 task involved consideration about oneself and others using socially descriptive adjectives. Both the ill and weight-recovered women with AN engaged medial prefrontal cortex less than healthy women for self-relevant cognitions, a potential biological trait difference. Weight-recovered women also activated the inferior frontal gyri and dorsal anterior cingulate more for direct self-evaluations than for reflected self-evaluations, unlike both other groups, suggesting that recovery may include compensatory neural changes related to social perspectives. The Faces task compared viewing oneself to a stranger. Participants with AN showed elevated activity in the bilateral fusiform gyri for self-images, unlike the weight-recovered and healthy women, suggesting cognitive distortions about physical appearance are a state rather than trait problem in this disease. Because both ill and recovered women showed neural differences related to social self-perception, but only recovered women differed when considering social perspectives, these neurocognitive targets may be particularly important for treatment., (© The Author (2016). Published by Oxford University Press.)

Objectives: Prior research suggests a possible association between pollen and suicide. No studies have examined the relationship between pollen and attempted suicide. This study examines the temporal association between airborne pollen counts and nonfatal suicidal and nonsuicidal self-directed violence (SDV) requiring an emergency department visit., Methods: Data on daily emergency department visits due to nonfatal SDV as identified by ICD-9 diagnosis criteria were extracted from emergency department medical records of Parkland Memorial Hospital in Dallas, Texas, between January 2000 and December 2003. Concurrent daily airborne tree, grass, and ragweed pollen data from the city of Dallas were extracted from the National Allergy Bureau online database. The data were analyzed using the time series method of generalized autoregressive conditional heteroskedasticity., Results: There were statistically significant and positive temporal associations between tree pollen counts and the number of nonfatal SDV events among women (P = .04) and between grass pollen counts and number of nonfatal SDV events among both men (P = .03) and women (P < .0001). There was no significant temporal association found between ragweed pollen counts and number of nonfatal SDV events., Conclusions: The study findings suggest that an increase in nonfatal SDV is associated with changes in tree and grass pollen counts. This is the first study that has examined an association between seasonal variation in tree and grass pollen levels and nonfatal SDV event data. The study also used a narrowly defined geographic area and temporal window. The findings suggest that pollen count may be a factor influencing seasonal patterns in suicidal behavior., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Specific personality traits have been linked with substance use disorders (SUDs), genetic mechanisms, and brain systems. Thus, determining the specificity of personality traits to types of SUD can advance the field towards defining SUD endophenotypes as well as understanding the brain systems involved for the development of novel treatments. Disentangling these factors is particularly important in highly co morbid SUDs, such as marijuana and nicotine use, so treatment can occur effectively for both. This study evaluated personality traits that distinguish isolated and co-morbid use of marijuana and nicotine. To that end, we collected the NEO Five Factor Inventory in participants who used marijuana-only (n=59), nicotine-only (n=27), both marijuana and nicotine (n=28), and in non-using controls (n=28). We used factor analyses to identify personality profiles, which are linear combinations of the five NEO Factors. We then conducted Receiver Operating Characteristics (ROC) curve analysis to test accuracy of the personality factors in discriminating isolated and co-morbid marijuana and nicotine users from each other. ROC curve analysis distinguished the four groups based on their NEO personality patterns. Results showed that NEO Factor 2 (openness, extraversion, agreeableness) discriminated marijuana and marijuana+nicotine users from controls and nicotine-only users with high predictability. Additional ANOVA results showed that the openness dimension discriminated marijuana users from nicotine users. These findings suggest that personality dimensions distinguish marijuana users from nicotine users and should be considered in prevention strategies., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: There are limited data on femoropopliteal artery stent thrombosis (ST), which is a serious adverse outcome of peripheral artery interventions., Methods and Results: Index procedures resulting in femoropopliteal ST were compared with stent procedures without subsequent ST in the Excellence in Peripheral Artery Disease registry. The study data had a total of 724 cases of stent procedures and 604 unique patients. Femoropopliteal ST occurred in 26 of 604 patients (4.3%) over a median follow-up of 6 months post procedure. ST was more likely to occur in men (96.3% versus 82.2%; P=0.026) and to have an initial intervention for chronic total occlusions (88.5% versus 64.0%; P=0.01). There was no significant difference in ST between drug-coated and bare-metal stents (4.4% versus 3.4%; P=0.55), but the rate of ST was significantly higher with self-expanding covered stent grafts compared with bare-metal stents (10.6% versus 3.4%; P=0.02). ST was significantly associated with an increased risk of 12-month major adverse limb events (hazard ratio, 4.99; 95% confidence interval, 2.31-10.77; P<0.001) compared with no ST. On multivariate analysis, treatment of chronic total occlusion lesions (odds ratio, 3.46; 95% confidence interval, 0.98-12.20; P=0.05) and in-stent restenosis lesions (odds ratio, 5.30; 95% confidence interval, 1.83-15.32; P=0.002) were independently associated with an increased risk of ST., Conclusions: In a multicenter peripheral interventional registry, femoropopliteal ST occurred in 4.3% of patients who underwent stent procedures, and it was associated with treatment of chronic total occlusions and in-stent restenosis lesions, and had higher 12-month major adverse limb events., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01904851., (© 2016 American Heart Association, Inc.)

Objective: This study explored the effects of media coverage of a terrorist incident in individuals remote from the location of a major attack who had directly experienced a prior terrorist incident., Method: Directly-exposed survivors of the 1995 Oklahoma City bombing, initially studied six months after the incident, and indirectly-affected Oklahoma City community residents were assessed two to seven months after the September 11, 2001, attacks. Survivors were assessed for a diagnosis of bombing-related posttraumatic stress disorder (PTSD) at index and follow up, and emotional reactions and September 11 media behavior were assessed in all participants., Results: Among the three investigated forms of media (television, radio, and newspaper), only television viewing was associated with 9/11-related posttraumatic stress reactions. Exposure to the Oklahoma City bombing was associated with greater arousal in relation to the September 11 attacks, and among survivors, having developed bombing-related PTSD was associated with higher scores on all three September 11 posttraumatic stress response clusters (intrusion, avoidance, and arousal). Although time spent watching television coverage of the September 11 attacks and fear-related discontinuation of media contact were not associated with Oklahoma City bombing exposure, discontinuing September 11 media contact due to fear was associated with avoidance/numbing in the full sample and in the analysis restricted to the bombing survivors., Conclusion: Surviving a prior terrorist incident and developing PTSD in relation to that incident may predispose individuals to adverse reactions to media coverage of a future terrorist attack., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Cocaine-induced neuroplastic changes may result in a heightened propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of basal neuronal activity, this study assessed alterations in rCBF and related resting state functional connectivity (rsFC) to prospectively predict relapse in patients following treatment for cocaine use disorder (CUD)., Methods: Pseudocontinuous arterial spin labeling functional magnetic resonance imaging and resting blood oxygen level-dependent functional magnetic resonance imaging data were acquired in the same scan session in abstinent participants with CUD before residential treatment discharge and in 20 healthy matched control subjects. Substance use was assessed twice weekly following discharge. Relapsed participants were defined as those who used stimulants within 30 days following treatment discharge (n = 22); early remission participants (n = 18) did not., Results: Voxel-wise, whole-brain analysis revealed enhanced rCBF only in the left posterior hippocampus (pHp) in the relapsed group compared with the early remission and control groups. Using this pHp as a seed, increased rsFC strength with the posterior cingulate cortex (PCC)/precuneus was seen in the relapsed versus early remission subgroups. Together, both increased pHp rCBF and strengthened pHp-PCC rsFC predicted relapse with 75% accuracy at 30, 60, and 90 days following treatment., Conclusions: In CUD participants at risk of early relapse, increased pHp basal activity and pHp-PCC circuit strength may reflect the propensity for heightened reactivity to cocaine cues and persistent cocaine-related ruminations. Mechanisms to mute hyperactivated brain regions and delink dysregulated neural circuits may prove useful to prevent relapse in patients with CUD., (Published by Elsevier Inc.)

In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=-0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids.

Although bipolar disorder and substance dependence are both associated with treatment non-adherence and cognitive impairment, no studies have investigated relationships between treatment adherence and cognitive functioning in this population. As part of a clinical trial, baseline performance on two neuropsychological tests in 120 outpatients with bipolar disorder and cocaine dependence was used to examine whether cognitive functioning was associated with appointment attendance, medication adherence, and return of medication bottles. This study found that higher baseline cognitive functioning measured by the Stroop Color-Word condition predicted better treatment adherence. However, this study also reports measurement sensitivity of cognition as it relates to treatment adherence when applied to this dual diagnosis population. Poorer performance in simple visual attention tasks as assessed by the Stroop Word condition was inversely associated with some measures of adherence. Future studies are warranted that include a comprehensive neuropsychological battery and advanced medication adherence measures to confirm these findings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Theory: We explored the theory that measures of medical students' well-being and stress from different types of preclinical curricula are linked with performance on standardized assessment., Hypotheses: Self-reported stress and quality of life among sophomore medical students having different types of preclinical curricula will vary in their relationships to USMLE Step 1 scores., Method: Voluntary surveys in 2010 and 2011 compared self-reported stress, physical and mental health, and quality of life with Step 1 scores for beginning sophomore students in the final year of a traditional, discipline-based curriculum and the 1st year of a revised, systems-based curriculum with changed grading system. Wilcoxon rank sum tests and Spearman rank correlations were used to analyze data, significant at p <.05., Results: New curriculum students reported worse physical health, subjective feelings, leisure activities, social relationships and morale, and more depressive symptoms and life stress than traditional curriculum students. However, among curriculum-related stressors, few differences emerged; revised curriculum sophomores reported less stress working with real and standardized patients than traditional students. There were no class differences in respondents' Step 1 scores. Among emotional and physical health measures, only feelings of morale correlated negatively with Step 1 performance. Revised curriculum students' Step 1 scores correlated negatively with stress from difficulty of coursework., Conclusions: Although revised curriculum students reported worse quality of life, general stress, and health and less stress from patient interactions than traditional students, few measures were associated with performance differences on Step 1. Moreover, curriculum type did not appear to either hinder or help students' Step 1 performance. To identify and help students at risk for academic problems, future assessments of correlates of Step 1 performance should be repeated after the new curriculum is well established, relating them also to performance on other standardized assessments of communication skills, professionalism, and later clinical evaluations in clerkships or internships.

This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3 Proc MIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007-.02) and SAD (P = .003-.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18-.55). All relative groups had hippocampal volumes not different from controls (P = .12-.97) and higher than those observed in probands (P = .003-.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64-.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51-.73, P < .05). These findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to examine psychiatric illness and physiological indicators in the children of Oklahoma City bombing survivors seven years after the event., Methods: A study of 17 Oklahoma City bombing survivors and their 21 adolescent and young-adult children conducted seven years after the disaster used structured diagnostic interviews to examine psychiatric outcomes. Physiological measurements included heart rate, systolic blood pressure, diastolic blood pressure, and physiological reactivity measured in response to a semi-structured bombing-reminder interview., Results: Results revealed a statistically significant positive association between survivors and their children with respect to both post-disaster and current posttraumatic stress disorder (PTSD). Also, children whose parents met diagnostic criteria for either post-disaster or current major depression were more likely to meet criteria for a post-disaster behavior disorder and for any post-disaster psychiatric disorder than children whose parents did not meet criteria for post-disaster or current major depression. Survivors' children meeting criteria for any post-disaster psychiatric diagnosis had higher heart rates during the pre-test, test, and post-test periods than children who did not meet criteria for any disorder. Children whose survivor parents met criteria for bombing-related PTSD and for any post-disaster psychiatric disorder had greater heart rate reactivity than those whose parents did not., Conclusion: Findings of this study support previous literature on the relationships between children's psychiatric illness and physiological reactions and suggest interactions between disaster survivors' psychiatric illness and their children's psychiatric and physiological status., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The study assessed survivors of Oklahoma City's 1995 bombing seven years postdisaster to identify long-term mental health service use., Methods: Psychiatric disorders and disaster-related variables were assessed for 99 survivors at seven years postdisaster with the Diagnostic Interview Schedule for DSM-IV and its Disaster Supplement., Results: Of the 99 survivors, 86% received services during the seven years. Use was associated with female sex, injury or hospitalization, and posttraumatic stress disorder (PTSD) or major depression. Informal interventions were usually initiated in the first six months. Treatment by psychiatrists, other professionals, and family doctors increased after the first month. Half the survivors with PTSD or depression received treatment from a psychiatrist. Only 15% of survivors took psychotropic medications. Although 33% received treatment for more than one year, only 7% were receiving services at seven years., Conclusions: Although service needs decreased over time, results support provision of diverse services adapted to changing needs.

Trauma is thought to interfere with normal grief by superimposing symptoms of posttraumatic stress disorder. This exploratory pilot study examined the association between traumatic grief and objectively measured physiological reactivity to a trauma interview in 73 children who lost relatives in the Oklahoma City bombing as well as a potential link between children and their maternal figures in physiological reactivity. Although the authors found no association between posttraumatic stress and objectively measured physiological reactivity among children, they found significant differences in objectively measured reactivity associated with loss and grief. Children who lost "close" relatives evidenced greater objectively measured reactivity than those who lost "distant" relatives. For the most part, children with higher levels of grief evidenced greater objectively measured reactivity than those with lower levels of grief. The most interesting of the findings was the parallel pattern in objectively measured physiological reactivity between children and their maternal figures along with a positive association between children's objectively measured physiological reactivity and maternal figures' self-reported physiological reactivity. Research using larger representative samples studied early and over time is indicated to determine the potential significance of these findings.