Among patients with peripheral artery disease (PAD), depression is diagnosed in 17-25% and negatively impacts wound healing, quality of life, and survival. We hypothesized that depression is ...underdiagnosed in patients with PAD. Additionally, given the associations between depression and mortality in PAD patients, there is an increased need to investigate the strength of this relationship. The present analysis includes 2 studies to address the following aims: (1) Investigation of the prevalence of concomitant PAD and depression in a cohort from the Southeastern United States, and (2) Examination of the association between depression and all-cause mortality in a cohort of Canadian patients with PAD.
STUDY 1: From June-August 2022, the Patient Health Questionnaire Module 9 (PHQ-9) was administered to all patients seeking PAD-related care including medical, wound/podiatric, or vascular interventional/surgical treatment, in the University of North Carolina-Chapel Hill Vascular, Wound, and Podiatry clinics. The PHQ-9 assesses symptoms over 2 weeks and is scored 0-27, with higher scores indicating increasingly severe depression. Demographics, primary diagnosis, depression history, and antidepressant prescription were determined through chart review. We compared the proportion of positive depression screenings (PHQ-9 ≥ 5) to known depression. Among those treated for depression, the PHQ-9 score severity was evaluated. T-tests and χ
tests were used to compare means and proportions. STUDY 2: From July 2015 to October 2016, the Geriatric Depression Scale Short Form was administered to adult patients with PAD undergoing revascularization. The Geriatric Depression Scale Short Form is a self-report measure of depression with a score >5 consistent with depression. The prevalence of depression was determined; primary outcome was all-cause mortality at 6 months.
STUDY 1: In 104 PAD patients (mean age 66.6 ± 11.3 years, 37% female), 37% of respondents scored ≥5 on the PHQ-9 survey, indicating at least mild depression. Only 18% of PAD patients had a history of depression, demonstrating a significant difference between the PHQ-9 findings and documented medical history. While depression was underdiagnosed in both men and women, men were more likely to have unrecognized depression (chi-squared statistic = 35.117, df = 1, P < 0.001). Among those with a history of depression, 74% had a current prescription for antidepressant medication, but 57% still had an elevated PHQ-9 score indicating possible undertreatment. STUDY 2: In 148 patients (mean age 70.3 ± 11.0 years, 39% female) the prevalence of screened depression was 28.4%, but only 3.3% had a documented history of depression suggesting significant underdiagnosis. Patients with depression were significantly more likely to die within 6 months of revascularization (9.5% vs. 0.9%; odds ratio 1.48, 95% confidence interval: 1.08 to 2.29). There was no association between depression and risk of length of stay, reintervention, or readmission.
Depression is underdiagnosed and undertreated among patients with PAD, which has grave consequences as it is associated with 1.5 times the odds of mortality within 6 months of revascularization. There is a critical need for more robust screenings and comprehensive mental health treatment for patients with concomitant depression and PAD.
The pedal medial arterial calcification (MAC) score has been associated with risk of major limb amputation in patients with chronic limb-threatening ischemia. This study aimed to validate the pedal ...MAC scoring system in a multi-institutional analysis to validate its usefulness in limb amputation risk prediction.
A multi-institution, retrospective study of patients who underwent endovascular or open surgical infrainguinal revascularization for chronic limb-threatening ischemia was performed. MAC scores of 0 to 5 were assigned based on visible calcified arteries on foot X ray then trichotomized (0-1, 2-4, 5) for analysis. The primary outcome was major limb amputation at 6 months. Adjusted Kaplan-Meier models were used to analyze time-to-major amputation across groups.
There were 176 patients with 184 affected limbs (mean age, 66 years; 61% male; 60% White), of whom 97% presented with a wound. The MAC score was 0 in 41%, 1 in 9%, 2 in 13%, 3 in 11%, 4 in 13%, and 5 in 13% of the limbs. There were 26 major amputations (14%) and 16 deaths (8.7%) within 6 months. Patients with MAC 5 had a significantly higher risk of major limb amputation than both the 0 to 1 and 2 to 4 groups (P = .001 and P = .044, respectively), and lower overall amputation-free survival (log-rank P = .008).
Pedal MAC score is a reproducible and generalizable measure of inframalleolar arterial disease that can be used with Wound, Ischemia, and foot Infection staging to predict major limb amputation in patients with chronic limb-threatening ischemia.
The traditionally reported outcomes for patients with ischemic wounds have centered on amputation-free survival. However, that discounts the importance of other patient-centered outcomes such as the ...wound healing time (WHT) and wound-free period (WFP). We evaluated the long-term wound outcomes of patients treated for chronic limb-threatening ischemia at our institution.
From 2014 to 2017, we identified all patients with chronic limb-threatening ischemia and ischemic wounds using symptomatic and hemodynamic criteria. The primary data included the wound size, wound location, WIfI (wound, ischemia, foot infection) grade, WHT, WFP, minor and major amputation, and death. Wounds were not considered healed if the patient had required a major amputation or had died before wound healing. The WHT was calculated as the interval in days between the diagnosis and determination of a healed wound. The WFP was calculated as the interval in days between a healed wound and wound recurrence, major amputation, death, or the end of the study period. A comparison of the wound healing parameters stratified by revascularization status was performed using the Student t test. A generalized linear model adjusted for age, sex, initial wound size, and WIfI grade was used to evaluate the risk of wound healing with and without revascularization.
A total of 256 patients had presented with 372 wounds. Of the 256 patients, 48% had undergone revascularization. During the study period, 97 minor amputations and 100 major amputations had been required, and 132 patients had died. The average wound size was 13.9 ± 52.0 cm2; however, for the 155 wounds that had healed, the average size was only 4.0 ± 9.6 cm2 (P = .002). No differences were found in the wound size when stratified by revascularization status (P = .727). Adjusted for the initial wound size, the risk of wound healing was not different when stratified by revascularization (risk ratio, 1.22; 95% confidence interval, 0.80-1.87; P = .354). For those whose wounds had healed, the average WHT and WFP were 173 ± 169 days and 775 ± 317 days, respectively. The WHT was not faster for the revascularized group (155 days vs 188 days; P = .221). When stratified by revascularization status, the rate of wound recurrence was 4.6 vs 8.9 wounds per 100 person-years for the revascularized and nonrevascularized groups, respectively (P = .125).
In our study, we found that, except for patients who presented with severe ischemia, revascularization was not associated with improved rates of wound healing. Among the wounds that healed, regardless of the initial ischemia grade, revascularization was not associated with a faster WHT or longer WFPs.
Precision medicine is a promising framework for generating evidence to improve health and health care. Yet, a gap persists between the ever-growing number of statistical precision medicine strategies ...for evidence generation and implementation in real-world clinical settings, and the strategies for closing this gap will likely be context-dependent. In this paper, we consider the specific context of partial compliance to wound management among patients with peripheral artery disease. Using a Gaussian process surrogate for the value function, we show the feasibility of using Bayesian optimization to learn optimal individualized treatment rules. Further, we expand beyond the common precision medicine task of learning an optimal individualized treatment rule to the characterization of classes of individualized treatment rules and show how those findings can be translated into clinical contexts.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
The decay mode B→K*ℓ+ℓ− is one of the most promising modes to probe physics beyond the standard model (SM), since the angular distribution of the decay products enables measurement of several ...constraining observables. LHCb has recently measured these observables using 3 fb−1 of data as a binned function of q2, the dilepton invariant mass squared. We find that LHCb data imply evidence for right-handed currents, which are absent in the SM. These conclusions are derived in the maximum q2 limit and are free from hadronic corrections. Our approach differs from other approaches that probe new physics at low q2 as it does not require estimates of hadronic parameters but relies instead on heavy quark symmetries that are reliable at the maximum q2 kinematic end point.
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The aim of this study was to evaluate the effect of fenestration configuration and fenestration gap on renal artery outcomes during fenestrated-branched endovascular aortic repair (F/BEVAR).
A ...retrospective multicenter analysis was performed, including patients with complex aortic aneurysms treated with F/BEVAR that incorporated at least one small fenestration to a renal artery. The renal fenestrations were divided into groups 1 (8 × 6 mm) and 2 (6 × 6 mm). Primary patency, target vessel instability (TVI), freedom from secondary interventions (SIs), occurrence of type IIIc endoleak, all related to the renal arteries, were analyzed at 30-day, 1-year, and 5-year landmarks. The fenestration gap (FG) distance was analyzed as a modifier, and clustering was addressed at the patient level.
A total of 796 patients were included in this study, 71.7% male, with a mean age of 73.3 ± 8.1 years. The mean follow-up was 30.0 ± 20.6 months. Of the 1474 small renal fenestrations analyzed, 47.6% were 8 × 6 mm, and 52.4% were 6 × 6 mm. At the 30-day landmark, primary patency (99.9% vs 98.0%; P value < .001 for groups 1 and 2, respectively), freedom from TVI (99.6% vs 97.1%; P value < .001 for groups 1 and 2, respectively), and freedom from SI (99.8% vs 98.4%; P value = .022 for groups 1 and 2, respectively) were higher in 8 × 6 compared with 6 × 6 fenestrations, and the incidence of acute kidney injury was similar across the groups (92.6% vs 92.7%; P value = .953 for groups 1 and 2 respectively). The primary patency at 1 and 5 years was higher in 8 × 6 fenestrations (1-year: 98.8% vs 96.9%; 5-year: 97.8% vs 95.7%, for groups 1 and 2, respectively, P values = .010 and .021 for 1 and 5 year comparisons, respectively). The freedom from SIs was significantly higher among 6 × 6 fenestrations at 5 years (93.1% vs 96.4%, for groups 1 and 2, respectively, P value = .007). The groups were equally as likely to experience a type Ic endoleak (1.3% and 1.6% for 8 × 6 and 6 × 6mm fenestrations, respectively, P = .689). The 6 × 6 fenestrations were associated with higher risk of kidney function deterioration (17.8%) when compared with 8 × 6 fenestrations (7.6%) at 5 years (P < .001). The risk of type IIIc endoleak was significantly higher among 8 × 6 fenestrations at 5 years (4.9% and 2% for 8 × 6 and 6 × 6 mm fenestrations, respectively; P = .005). A FG ≥5 mm negatively impacted the cumulative 5-year freedom from TVI (group 1: FG ≥5 mm = 0.714, FG <5 mm = 0.857; P < .001; group 2: FG ≥5 mm = 0.761, FG <5 mm = 0.929; P < .001) and the cumulative 5-year freedom from type IIIc endoleak (group 1: FG ≥5 mm = 0.759, FG <5 mm = 0.921; P = .034; group 2: FG ≥5 mm = 0.853, FG <5 mm = 0.979; P < .001) in both groups and the cumulative 5-year patency in group 2 (group 1: FG ≥5 mm = 0.963, FG <5 mm = 0.948; P = .572; group 2: FG ≥5 mm = 0.905, FG <5 mm = 0.938; P = .036).
Fenestration configuration for the renal arteries impacts outcomes. The 8 × 6 small fenestrations have better patency at 30 days, 1 year, and 5 years, whereas 6 × 6 small fenestrations are associated with lower rates of SIs, primarily due to a lower incidence of type IIIc endoleaks. FG ≥5 mm at the level of the renal arteries significantly impacts the freedom from TVI, freedom from type IIIc endoleak, and 5-year patency independently of the fenestration size or vessel diameter.
Females with peripheral arterial disease (PAD) treated with endovascular interventions have increased limb-based procedural complications compared to males. Little is known regarding long-term ...bleeding risk in these patients who often require long-term antiplatelet or anticoagulation therapy. We hypothesize that females have a higher incidence of bleeding events compared to males in the year following endovascular intervention for PAD.
Adults (≥65 years) who underwent endovascular revascularization for PAD between 2008-2015 in Medicare claims data were identified. Patients were allocated by prescribed post-procedural antithrombotic therapy including 1) antiplatelet therapy, 2) anticoagulation therapy, 3) dual antiplatelet and anticoagulation therapy, and 4) no prescription antithrombotic therapy. Bleeding events were classified as gastrointestinal, intracranial, hematoma, airway, or other. Crude and covariate-standardized 30-, 90- and 365 days cumulative incidence of bleeding events, overall and by sex, were estimated using Aalen-Johansen estimators accounting for death as a competing risk. Sex differences were identified using Gray’s test.
Of 31,593 eligible patients, 54% were females. Females were older (77.9 vs 75.5 years) and tended to use antiplatelet therapy more often at 30-, 90- and 365 days post-intervention. Clopidogrel was the most prescribed antiplatelet, and 32% of patients continued its use at 365 days. Anticoagulants were prescribed to 26% of patients at the time of the procedure, and only 8.8% continued anticoagulation at 365 days. Thirty-one percent of patients were diagnosed with a bleeding event within 1-year after intervention. Cumulative incidence of any bleeding event during the post-intervention period was higher in females compared to males with a risk difference of 3% between sex cohorts (p<0.01). Specifically, females had a higher incidence of GI bleed and hematoma (p<0.01), but a lower incidence of airway-related bleeding at each time point compared to males (p<0.01).
Sex disparities in bleeding complications following endovascular intervention for PAD persist long-term. Females are more likely to be readmitted with a bleeding complication up to one-year post-procedure. Antithrombotic therapy disproportionately increases the risk of bleeding in females. Further research is necessary to understand the mechanisms responsible for abnormal coagulopathy in females post endovascular therapy.
Females experienced significantly more long-term bleeding complications in this retrospective Medicare claims cohort study of 31,593 patients undergoing endovascular intervention for infrainguinal peripheral arterial disease. The authors suggest that increased awareness and careful consideration of antithrombotic utilization, specifically in female patients, is necessary to reduce sex-based differences in postoperative outcomes.
The measurement of two-particle angular correlation functions in high-multiplicity e^{+}e^{-} collisions at sqrts=10.52 GeV is reported. In this study, the 89.5 fb^{-1} of hadronic e^{+}e^{-} ...annihilation data collected by the Belle detector at KEKB are used. Two-particle angular correlation functions are measured in the full relative azimuthal angle (Δϕ) and three units of pseudorapidity (Δη), defined by either the electron beam axis or the event-shape thrust axis, and are studied as a function of charged-particle multiplicity. The measurement in the thrust axis analysis, with mostly outgoing quark pairs determining the reference axis, is sensitive to the region of additional soft gluon emissions. No significant anisotropic collective behavior is observed with either coordinate analyses. Near-side jet correlations appear to be absent in the thrust axis analysis. The measurements are compared to predictions from various event generators and are expected to provide new constraints to the phenomenological models in the low-energy regime.
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We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,μ), using the full data sample of 772×10^{6} BBover ¯ pairs recorded by the Belle detector at the KEKB ...asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.
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We report on a search for a heavy Majorana neutrino in the decays τ^{-}→π^{-}ν_{h}, ν_{h}→π^{±}ℓ^{∓}, ℓ=e, μ. The results are obtained using the full data sample of 988 fb^{-1} collected with the ...Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider, which contains 912×10^{6} ττ pairs. We observe no significant signal and set 95% CL upper limits on the couplings of the heavy right-handed neutrinos to the conventional standard model left-handed neutrinos in the mass range 0.2-1.6 GeV/c^{2}. This is the first study of a mixed couplings of heavy neutrinos to τ leptons and light-flavor leptons.
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