Trends and Factors Associated With Peripheral Vascular Interventions for the Treatment of Claudication From 2011 to 2022: A National Medicare Cohort Study.

BACKGROUND: Previous cross-sectional studies have identified wide practice pattern variations in the use of peripheral vascular interventions (PVIs) for the treatment of claudication. However, there are limited data on longitudinal practice patterns. We aimed to describe the temporal trends and charges associated with PVI use for claudication over the past 12 years in the United States. METHODS AND RESULTS: We conducted a retrospective analysis using 100% Medicare fee-for-service claims data to identify all patients who underwent a PVI for claudication between January 2011 and December 2022. We evaluated the trends in utilization and Medicare-allowed charges of PVI according to anatomic level, procedure type, and intervention settings using generalized linear models. Multinomial logistic regressions were used to evaluate factors associated with different levels and types of PVI. We identified 599 197 PVIs performed for claudication. The proportional use of tibial PVI increased 1.0% per year, and atherectomy increased by 1.6% per year over the study period. The proportion of PVIs performed in ambulatory surgical centers/office-based laboratories grew at 4% per year from 12.4% in 2011 to 55.7% in 2022. Total Medicare-allowed charges increased by $11 980 035 USD/year. Multinomial logistic regression identified significant associations between race and ethnicity and treatment setting with use of both atherectomy and tibial PVI. CONCLUSIONS: The use of tibial PVI and atherectomy for the treatment of claudication has increased dramatically in in ambulatory surgical center/office-based laboratory settings, non-White patients, and resulting in a significant increase in health care charges. There is a critical need to improve the delivery of value-based care for the treatment of claudication.

Investigating Unconscious Race Bias and Bias Awareness Among Vascular Surgeons.

Background: Implicit bias can influence behavior and decision-making. In clinical settings, implicit bias may influence treatment decisions and contribute to health disparities. Given documented Black-White disparities in vascular care, the purpose of this study was to examine the prevalence and degree of unconscious bias and awareness of bias among vascular surgeons treating peripheral artery disease (PAD). Methods: The sampling frame included all vascular surgeons who participate in the Vascular Quality Initiative (VQI). Participants completed a survey which included demographic questions, the race implicit association test (IAT) to measure magnitude of unconscious bias, and six bias awareness questions to measure conscious bias. The magnitude of unconscious bias was no preference; or slight, moderate, or strong in the direction of pro-White or pro-Black. Data from participants were weighted to account for nonresponse bias and known differences in the characteristics of surgeons who chose to participate compared to the full registry. We stratified unconscious and conscious findings by physician race/ethnicity, physician sex, and years of experience. Finally, we examined the relationship between unconscious and conscious bias. Results: There were 2,512 surgeons in the VQI registry, 304 of whom completed the survey, including getting IAT results. Most participants (71.6%) showed a pro-White bias with 73.0% of this group in the moderate and strong categories. While 77.5% of respondents showed conscious awareness of bias, of those whose conscious results showed lack of awareness, 67.8% had moderate or strong bias, compared to 55.7% for those with awareness. Bias magnitude varied based on physician race/ethnicity and years of experience. Women were more likely than men to report awareness of biases and potential impact of bias on decision-making. Conclusions: Most people have some level of unconscious bias, developed from early life reinforcements, social stereotypes, and learned experiences. Regarding health disparities, however, these are important findings in a profession that takes care of patients with PAD due to heavy burden of comorbid conditions and high proportion of individuals from structurally vulnerable groups. Given the lack of association between unconscious and conscious awareness of biases, awareness may be an important first step in mitigation to minimize racial disparities in healthcare.

Infrapopliteal Peripheral Vascular Interventions for Claudication are Performed Frequently in the USA and Are Associated with Poor Long Term Outcomes.

OBJECTIVE: Infrapopliteal peripheral vascular interventions (PVIs) for claudication are still performed in the USA. This study aimed to evaluate whether infrapopliteal PVI is associated with worse long term outcomes than isolated femoropopliteal PVI for treatment of claudication. METHODS: A retrospective analysis of fee for service claims in a national administrative database was conducted using 100% of the Medicare fee for service claims between 2017 and 2019 to capture all Medicare beneficiaries who underwent an index infra-inguinal PVI for claudication. Hierarchical Cox proportional hazards models were performed to assess the association of infrapopliteal PVI with conversion to chronic limb threatening ischaemia (CLTI), repeat PVI, and major amputation. RESULTS: In total, 36 147 patients (41.1% female; 89.7% age ≥ 65 years; 79.0% non-Hispanic White race) underwent an index PVI for claudication, of whom 32.6% (n = 11 790) received an infrapopliteal PVI. Of these, 61.4% (n = 7 245) received a concomitant femoropopliteal PVI and 38.6% (n = 4 545) received an isolated infrapopliteal PVI. The median follow up time was 3.5 years (interquartile range 2.7, 4.3). Patients receiving infrapopliteal PVI had a higher three year cumulative incidence of conversion to CLTI (26.0%; 95% confidence interval [CI] 24.9 - 27.2% vs. 19.9%; 95% CI 19.1 - 20.7%), repeat PVI (56.0%; 95% CI 54.8 - 57.3% vs. 45.7%; 95% CI 44.9 - 46.6%), and major amputation (2.2%; 95% CI 1.8 - 2.6% vs. 1.3%; 95% CI 1.1 - 1.5%) compared with patients receiving isolated femoropopliteal PVI. After adjusting for patient and physician level characteristics, the risk of conversion to CLTI (adjusted hazard ratio [aHR] 1.31, 95% CI 1.23 - 1.39), repeat PVI (aHR 1.12, 95% CI 1.05 - 1.20), and major amputation (aHR 1.72, 95% CI 1.42 - 2.07) remained significantly higher for patients receiving infrapopliteal PVI. An increasing number of infrapopliteal vessels treated during the index intervention was associated with increasingly poor outcomes (p < .001 for trend). CONCLUSION: Infrapopliteal PVI for claudication is associated with worse long term outcomes relative to isolated femoropopliteal PVI.

Infrapopliteal Endovascular Interventions for Claudication Are Associated with Poor Long-Term Outcomes in Medicare-Matched Registry Patients.

BACKGROUND: There are limited data supporting or opposing the use of infrapopliteal peripheral vascular interventions (PVI) for the treatment of claudication. OBJECTIVES: We aimed to evaluate the association of infrapopliteal PVI with long-term outcomes compared with isolated femoropopliteal PVI for the treatment of claudication. METHODS: We conducted a retrospective analysis of all patients in the Medicare-matched Vascular Quality Initiative database who underwent an index infrainguinal PVI for claudication from January 2004-December 2019 using Cox proportional hazards models. RESULTS: Of 14,261 patients (39.9% female; 85.6% age ≥65 years, 87.7% non-Hispanic white) who underwent an index infrainguinal PVI for claudication, 16.6% (N=2,369) received an infrapopliteal PVI. The median follow-up after index PVI was 3.7 years (IQR 2.1-6.1). Compared to patients who underwent isolated femoropopliteal PVI, patients receiving any infrapopliteal PVI had a higher 3-year cumulative incidence of conversion to CLTI (33.3% vs. 23.8%; P<0.001); repeat PVI (41.0% vs. 38.2%; P<0.01); and amputation (8.1% vs. 2.8%; P<0.001). After risk-adjustment, patients undergoing infrapopliteal PVI had a higher risk of conversion to CLTI (aHR 1.39, 95% CI, 1.25-1.53); repeat PVI (aHR 1.10, 95% CI, 1.01-1.19); and amputation (aHR 2.18, 95% CI, 1.77-2.67). Findings were consistent after adjusting for competing risk of death; in a 1:1 propensity-matched analysis; and in subgroup analyses stratified by TASC disease, diabetes, and end-stage kidney disease. CONCLUSIONS: Infrapopliteal PVI is associated with worse long-term outcomes than femoropopliteal PVI for claudication. These risks should be discussed with patients.

Investigating the impact of suboptimal prescription of preoperative antiplatelets and statins on race and ethnicity-related disparities in major limb amputation.

BACKGROUND: Non-Hispanic Black and Hispanic patients with symptomatic PAD may receive different treatments than White patients with symptomatic PAD. The delivery of guideline-directed medical treatment may be a modifiable upstream driver of race and ethnicity-related disparities in outcomes such as limb amputation. The purpose of our study was to investigate the prescription of preoperative antiplatelets and statins in producing disparities in the risk of amputation following revascularization for symptomatic peripheral artery disease (PAD). METHODS: We used data from the Vascular Quality Initiative, a vascular procedure-based registry in the United States (2011-2018). We estimated the probability of preoperative antiplatelet and statin prescriptions and 1-year incidence of amputation. We then estimated the amputation risk difference between race/ethnicity groups that could be eliminated under a hypothetical intervention. RESULTS: Across 100,579 revascularizations, the 1-year amputation risk was 2.5% (2.4%, 2.6%) in White patients, 5.3% (4.9%, 5.6%) in Black patients, and 5.3% (4.7%, 5.9%) in Hispanic patients. Black (57.5%) and Hispanic patients (58.7%) were only slightly less likely than White patients (60.9%) to receive antiplatelet and statin therapy. However, the effect of antiplatelets and statins was greater in Black and Hispanic patients such that, had all patients received these medications, the estimated risk difference comparing Black to White patients would have reduced by 8.9% (-2.9%, 21.9%) and the risk difference comparing Hispanic to White patients would have been reduced by 17.6% (-0.7%, 38.6%). CONCLUSION: Even though guideline-directed care appeared evenly distributed by race/ethnicity, increasing access to such care may decrease health care disparities in major limb amputation.

Prevalence of and Risk Factors for Peripheral Artery Disease in Rural South Africa: A Cross-Sectional Analysis of the HAALSI Cohort.

BACKGROUND: The burden of peripheral artery disease (PAD) is increasing in low- and middle-income countries. Existing literature from sub-Saharan Africa is limited and lacks population-representative estimates. We estimated the burden and risk factor profile of PAD for a rural South African population. METHODS AND RESULTS: We used data from 1883 participants from a rural, low-income cohort of South African adults aged 40 to 69 years with available ankle-brachial index measurements. We defined clinical PAD as ankle-brachial index ≤0.90 or >1.40, and borderline PAD as ankle-brachial index >0.90 and ≤1.00. We compared the distribution of sociodemographic variables, biomarkers, and comorbidities across PAD classifications. To identify associated factors, we calculated unadjusted and age-sex-adjusted prevalence ratios (PRs) with log-binomial models. Overall, 6.6% (95% CI, 5.6-7.7) of the sample met the diagnostic criteria for clinical PAD, while 44.7% (95% CI, 42.4-47.0) met the diagnostic criteria for borderline PAD. Age (PR: 1.9 [95% CI, 1.2-3.1] for ages 50-59 years compared with 40-49 years; PR: 2.5 [95% CI, 1.5-4.0] for ages 60-69 years compared with 40-49 years); diagnosed hypertension (PR: 1.53 [95% CI, 1.08-2.17]); and C-reactive protein (PR: 1.08 [95% CI, 1.03-1.12]) were associated with increased prevalence of clinical PAD. All other examined factors were not significantly associated with clinical PAD. CONCLUSIONS: We found high PAD prevalence for younger age groups compared with previous research and a lack of statistical evidence for the influence of traditional risk factors for this rural, low-income population. Future research should focus on identifying the underlying risk factors for PAD in this setting. South African policymakers and clinicians should consider expanded screening for early PAD detection in rural areas.

Sex differences in outcomes of exercise therapy for patients with intermittent claudication: A scoping review.

Exercise therapy is first-line treatment for intermittent claudication due to peripheral artery disease. We sought to synthesize the literature on sex differences in response to exercise therapy for the treatment of intermittent claudication due to peripheral artery disease. A scoping review was performed (1997 to 2023) using Ovid MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase, SPORTDiscus, and Web of Science. Articles were included if they were a scientific report of any measures of health-related quality of life or walking performance after an intervention that included a structured walking program. Of the 13 studies, 11 included measures of walking distance; 7 included measures of walking time, 5 included measures of walking speed, and 4 included quality of life measures. Overall, exercise therapy resulted in significant improvements across most measures of walking performance for both men and females. When comparing magnitudes of outcome improvement by sex, results of walking-based measures were contradictory; some studies noted no difference and others found superior outcomes for men. Results of quality of life-based measures were also contradictory, with some finding no difference and others reporting substantially more improvement for females. Both men and females experienced considerable improvement in walking performance and quality of life with exercise therapy. Evidence regarding the differential effect of exercise therapy on outcomes by sex for intermittent claudication is limited and contradictory. Further efforts should be directed at using standardized interventions and metrics for measuring the outcomes that match the indications for intervention in these patients to better understand the expected benefits and any variance according to sex.

Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021.

Background: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. Methods: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. Results: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. Conclusions: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. Clinical Trials Registration: NCT04811664.

Disparities in healthcare utilization by insurance status among patients with symptomatic peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) is a common circulatory disorder associated with increased hospitalizations and significant health care-related expenditures. Among patients with PAD, insurance status is an important determinant of health care utilization, treatment of disease, and treatment outcomes. However, little is known about PAD-costs differences across different insurance providers. In this study we examined possible disparities in length of stay and total charge of inpatient hospitalizations among patients with PAD by insurance type. METHODS: We conducted a cross-sectional analysis of length of stay and total charge by insurance provider for all hospitalizations for individuals with PAD in South Carolina (2010-2018). Cross-classified multilevel modeling was applied to account for the non-nested hierarchical structure of the data, with county and hospital included as random effects. Analyses were adjusted for patient age, race/ethnicity, county, year of admission, admission type, all-patient refined diagnostic groups, and Charlson comorbidity index. RESULTS: Among 385,018 hospitalizations for individuals with PAD in South Carolina, the median length of stay was 4 days (IQR: 5) and the median total charge of hospitalization was $43,232 (IQR: $52,405). Length of stay and total charge varied significantly by insurance provider. Medicare patients had increased length of stay (IRR = 1.08, 95 CI%: 1.07, 1.09) and higher total charges (ß: 0.012, 95% CI: 0.007, 0.178) than patients with private insurance. Medicaid patients also had increased length of stay (IRR = 1.26, 95% CI: 1.24,1.28) but had lower total charges (ß: -0.022, 95% CI: -0.003. -0.015) than patients with private insurance. CONCLUSIONS: Insurance status was associated with inpatient length of stay and total charges in patients with PAD. It is essential that Medicare and Medicaid individuals with PAD receive proper management and care of their PAD, particularly in the primary care settings, to prevent hospitalizations and reduce the excess burden on these patients.

The association between socioeconomic distress communities index and amputation among patients with peripheral artery disease.

Background: Socioeconomic factors have been shown to be associated with amputation in peripheral artery disease (PAD); however, analyses have normally focused on insurance status, race, or median income. We sought to determine whether community-level socioeconomic distress was associated with major amputation and if that association differed by race. Materials and methods: Community-level socioeconomic distress was measured using the distressed communities index (DCI). The DCI is a zip code level compositive socioeconomic score (0-100) that accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. A distressed community was defined as a zip code with DCI of 40 or greater. We calculated one-year risk of major amputation by DCI score for individuals with peripheral artery disease in South Carolina, 2012-2017. Treating death as competing event, we reported Fine and Gray subdistribution hazards ratios (sdHR), adjusted for patient demographic and clinical comorbidities associated with amputation. Further analyses were completed to identify potential differences in outcomes within strata of race and DCI. Results: Among 82,848 individuals with peripheral artery disease, the one-year incidence of amputation was 3.5% (95% CI: 3.3%, 3.6%) and was significantly greater in distressed communities than non-distressed communities (3.9%; 95% CI: 3.8%, 4.1% vs. 2.4%; 95% CI: 2.2%, 2.6%). After controlling for death and adjusting for covariates, we found an increased hazard of amputation among individuals in a distressed community (sdHR: 1.25; 95% CI: 1.14, 1.37), which persisted across racial strata. However, regardless of DCI score, Black individuals had the highest incidence of amputation. Conclusion: Socioeconomic status is independently predictive of limb amputation after controlling for demographic characteristics and clinical comorbidities. Race continues to be an important risk factor, with Black individuals having higher incidence of amputation, even in non-distressed communities, than White individuals had in distressed communities.

Surgical site infection after open lower extremity revascularization associated with doubled rate of major limb amputation.

OBJECTIVE: Surgical site infection (SSI) after open lower extremity revascularization is a relatively common complication associated with increased hospital stays, graft infection, and in severe cases, graft loss. Although the short-term effects of SSI can be significant, it has not been considered a complication that increases major limb amputation. The purpose of this study was to determine the association of SSI with outcomes in patients undergoing surgical revascularization for peripheral arterial disease. METHODS: We analyzed nationwide Vascular Quality Initiative (VQI) data from the infrainguinal bypass module from 2003 to 2017. The cohort included adults who underwent open lower extremity bypass for symptomatic peripheral arterial disease and had at least one follow-up record. Weighted Kaplan-Meier curves and Cox proportional hazards regression were used to assess the association between SSI and 1-year mortality and major limb amputation. Inverse-probability of treatment weights were used to account for differences in demographics and patient characteristics and allow for 'adjusted' Kaplan-Meier curves. RESULTS: The analysis included 21,639 patients, and 1155 (5%) had a reported SSI within 30 days of surgery. Patients with SSI were more likely be obese (41% vs 30%), but there were no other clinically relevant differences between demographics, comorbidities, and bypass details. After weighting, patients with SSI were almost twice as likely to undergo major amputation by 6 months (hazard ratio, 1.84; 95% confidence interval, 1.07-3.17). The association with SSI and increased amputation rates persisted at 1 year. The association of SSI on amputation was no different based on preoperative Rutherford class (P = .91). The association between SSI and 1-year mortality rate was not statistically significant (hazard ratio, 1.15; 95% confidence interval, 0.91-1.46). CONCLUSIONS: SSI is more common in obese patients, and patients who develop an SSI are observed to have a significantly increased rate of limb amputation after open lower extremity revascularization.

Implementation of a Rural Community Diagnostic Testing Strategy for SARS-CoV-2 in Upstate South Carolina.

By developing a partnership amongst a public university lab, local city government officials and community healthcare providers, we established a drive-through COVID-19 testing site aiming to improve access to SARS-CoV-2 testing in rural Upstate South Carolina. We collected information on symptoms and known exposures of individuals seeking testing to determine the number of pre- or asymptomatic individuals. We completed 71,102 SARS-CoV-2 tests in the community between December 2020-December 2021 and reported 91.49% of results within 24 h. We successfully identified 5,244 positive tests; 73.36% of these tests originated from individuals who did not report symptoms. Finally, we identified high transmission levels during two major surges and compared test positivity rates of the local and regional communities. Importantly, the local community had significantly lower test positivity rates than the regional community throughout 2021 (p < 0.001). While both communities reached peak case load and test positivity near the same time, the local community returned to moderate transmission as indicated by positivity 4 weeks before the regional community. Our university lab facilitated easy testing with fast turnaround times, which encouraged voluntary testing and helped identify a large number of non-symptomatic cases. Finding the balance of simplicity, accessibility, and community trust was vital to the success of our widespread community testing program for SARS-CoV-2.

Predicting COVID-19 Infected Individuals in a Defined Population from Wastewater RNA Data.

Wastewater surveillance of SARS-CoV-2 RNA has become an important tool for tracking the presence of the virus and serving as an early indicator for the onset of rapid transmission. Nevertheless, wastewater data are still not commonly used to predict the number of infected individuals in a sewershed. The main objective of this study was to calibrate a susceptible-exposed-infectious-recovered (SEIR) model using RNA copy rates in sewage (i.e., gene copies per liter times flow rate) and the number of SARS-CoV-2 saliva-test-positive infected individuals in a university student population that was subject to repeated weekly testing during the Spring 2021 semester. A strong correlation was observed between the RNA copy rates and the number of infected individuals. The parameter in the SEIR model that had the largest impact on calibration was the maximum shedding rate, resulting in a mean value of 7.72 log10 genome copies per gram of feces. Regressing the saliva-test-positive infected individuals on predictions from the SEIR model based on the RNA copy rates yielded a slope of 0.87 (SE=0.11), which is statistically consistent with a 1:1 relationship between the two. These findings demonstrate that wastewater surveillance of SARS-CoV-2 can be used to estimate the number of infected individuals in a sewershed.

Non-Hispanic Black and Hispanic Patients Have Worse Outcomes Than White Patients Within Similar Stages of Peripheral Artery Disease.

Background Racial and ethnic disparities in outcomes following lower limb revascularization for peripheral artery disease have been ascribed to disease severity at presentation for surgery. Methods and Results We calculated 1-year risk of major adverse limb events (MALEs), major amputation, and death for patients undergoing elective revascularization for claudication or chronic limb-threatening ischemia in the Vascular Quality Initiative data (2011-2018). We report hazard ratios according to race and ethnicity using Cox (death) or Fine and Gray subdistribution hazards models (MALE and major amputation, treating death as a competing event), adjusted for patient, treatment, and anatomic factors associated with disease severity. Among 88 599 patients (age, 69 years; 37% women), 1-year risk of MALE (major amputation and death) was 12.8% (95% CI, 12.5-13.0) in 67 651 White patients, 16.5% (95% CI, 5.8-7.8) in 15 442 Black patients, and 17.2% (95% CI, 5.6-6.9) in 5506 Hispanic patients. Compared with White patients, we observed an increased hazard of poor limb outcomes among Black (MALE: 1.17; 95% CI, 1.12-1.22; amputation: 1.52; 95% CI, 1.39-1.65) and Hispanic (MALE: 1.22; 95% CI, 1.14-1.31; amputation: 1.45; 95% CI, 1.28-1.64) patients. However, Black and Hispanic patients had a hazard of death of 0.85 (95% CI, 0.79-0.91) and 0.71 (95% CI, 0.63-0.79) times the hazard among White patients, respectively. Worse limb outcomes were observed among Black and Hispanic patients across subcohorts of claudication and chronic limb-threatening ischemia. Conclusions Black and Hispanic patients undergoing infrainguinal revascularization for chronic limb-threatening ischemia and claudication had worse limb outcomes compared with White patients, even with similar disease severity at presentation. Additional investigation aimed at eliminating disparate limb outcomes is needed.

Ankle-Brachial Index and Subsequent Risk of Severe Ischemic Leg Outcomes: The ARIC Study.

Background Ankle-brachial index (ABI) is used to identify lower-extremity peripheral artery disease (PAD). However, its association with severe ischemic leg outcomes (eg, amputation) has not been investigated in the general population. Methods and Results Among 13 735 ARIC (Atherosclerosis Risk in Communities) study participants without clinical manifestations of PAD (mean age, 54 [SD, 5.8] years; 44.4% men; and 73.6% White) at baseline (1987-1989), we quantified the prospective association between ABI and subsequent severe ischemic leg outcomes, critical limb ischemia (PAD with rest pain or tissue loss) and ischemic leg amputation (PAD requiring amputation) according to discharge diagnosis. Over a median follow-up of ≈28 years, there were 221 and 129 events of critical limb ischemia and ischemic leg amputation, respectively. After adjusting for demographics, ABI ≤0.90 versus 1.11 to 1.20 had a ≈4-fold higher risk of critical limb ischemia and ischemic leg amputation (hazard ratios, 3.85 [95% CI, 2.09-7.11] and 4.39 [95% CI, 2.08-9.27]). The magnitude of the association was modestly attenuated after multivariable adjustment (hazard ratios, 2.44 [95% CI, 1.29-4.61] and 2.72 [95% CI, 1.25-5.91], respectively). ABI 0.91 to 1.00 and 1.01 to 1.10 were also associated with these severe leg outcomes, with hazard ratios ranging from 1.7 to 2.0 after accounting for potential clinical and demographic confounders. The associations were largely consistent across various subgroups. Conclusions In a middle-aged community-based cohort, lower ABI was independently and robustly associated with increased risk of severe ischemic leg outcomes. Our results further support ABI ≤0.90 as a threshold diagnosing PAD and also suggest the importance of recognizing the prognostic value of ABI 0.91 to 1.10 for limb prognosis.

Ankle-brachial index and subsequent risk of incident and recurrent cardiovascular events in older adults: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: The ankle-brachial index (ABI) is a diagnostic test for screening and detecting peripheral artery disease (PAD), as well as a risk enhancer in the AHA/ACC guidelines on the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, our understanding of the association between ABI and cardiovascular risk in contemporary older populations is limited. Additionally, the prognostic value of ABI among individuals with prior ASCVD is not well understood. METHODS: Among 5,003 older adults at ARIC visit 5 (2011-2013) (4,160 without prior ASCVD [median age 74 years, 38% male], and 843 with ASCVD [median age 76 years, 65% male]), we quantified the association between ABI and the risk of heart failure (HF), and composite coronary heart disease and stroke (CHD/stroke) using multivariable Cox regression models. RESULTS: Over a median follow-up of 5.5 years, we observed 400 CHD/stroke events and 338 HF cases (242 and 199 cases in those without prior ASCVD, respectively). In participants without a history of ASCVD, a low ABI ≤0.9 (relative to ABI 1.11-1.20) was associated with both CHD/stroke and HF (adjusted hazard ratios 2.40 [95% CI: 1.55-3.71] and 2.23 [1.40-3.56], respectively). In those with prior ASCVD, low ABI was not significantly associated with CHD/stroke, but was with HF (7.12 [2.47-20.50]). The ABI categories of 0.9-1.2 and > 1.3 were also independently associated with increased HF risk. Beyond traditional risk factors, ABI significantly improved the risk discrimination of CHD/stroke in those without ASCVD and HF, regardless of baseline ASCVD. CONCLUSIONS: Low ABI was associated with CHD/stroke in those without prior ASCVD and higher risk of HF regardless of baseline ASCVD status. These results support ABI as a risk enhancer for guiding primary cardiovascular prevention and suggest its potential value in HF risk assessment for older adults.

Healthy volunteers in US phase I clinical trials: Sociodemographic characteristics and participation over time.

BACKGROUND: Increasing the diversity of research participants is an important focus of clinical trials. However, little is known regarding who enrolls as healthy volunteers in Phase I clinical trials, which test the safety and tolerability of investigational new drugs. Despite the risk, healthy volunteers can derive no medical benefit from their participation, and they are financially compensated for enrolling. OBJECTIVE: This study's purpose is to describe sociodemographic characteristics and clinical trial participation histories of healthy people who enroll in US Phase I trials. METHODS: The HealthyVOICES Project (HVP) is a longitudinal study of healthy individuals who have enrolled in Phase I trials. We describe self-reported sociodemographic information and Phase I trial history from HVP recruitment (May-December 2013) through the project's end three years later (December 2016). Trial experiences are presented as medians and quartiles. RESULTS: The HVP included 178 participants. Nearly three-fourths of participants were male, and two-thirds were classified as racial and ethnic minorities. We found that some groups of participants were more likely to have completed a greater number of clinical trials over a longer timeframe than others. Those groups included participants who were male, Black, Hispanic, 30-39-years-old, unemployed, had received vocational training in a trade, or had annual household incomes of less than $25,000. Additionally, the greater the number of clinical trials participants had completed, the more likely they were to continue screening for new trials over the course of three years. Participants who pursued clinical trials as a full-time job participated in the greatest number of trials and were the most likely to continuing screening over time. IMPLICATIONS: Participation as a healthy volunteer in US Phase I trials is driven by social inequalities. Disadvantaged groups tend to participate in a greater number of clinical trials and participate longer than more privileged groups.

Precision Medicine Enables More TNM-Like Staging in Patients With Chronic Limb Threatening Ischemia.

Introduction: In cancer, there are survival-based staging systems and tailored, stage-based treatments. There is little personalized treatment in vascular disease. The 2019 Global Vascular Guidelines on the Management of CLTI proposed successful treatment hinges upon Patient risk, Limb severity, and ANatomic complexity (PLAN). We sought to confirm a three axis approach and define how increasing severity affects mortality, not just limb loss. Methods: Patients revascularized for incident CLTI at our institution from 2013 to 2017 were included. Outcomes were mortality, limb loss, the composite endpoint of amputation-free survival. Using Bayesian machine learning, specifically supervised topic modeling, clusters of patient features associated with mortality were formed after controlling for revascularization type. Patients were assigned to the cluster they belonged to with highest probability; clusters were characterized by analyzing the characteristics of patients within them. Patient outcomes were used to order the clusters into stages with increasing mortality. Results: We defined three distinct clusters as the basis for patient- and limb-centered stages. Across stages, rates of 1-year mortality were 7.6, 13.8, 18.9% and rates of amputation-free survival were 84.8, 79.3, and 63.2%. Stage one had patients with rest pain and previous revascularization who were less likely to have wounds, diabetes, and renal disease. Stage two had doubled mortality, likely related to diabetes prevalence. Stage three is characterized by high rates of complicated comorbidities, particularly end stage renal disease, and significantly higher rate of limb loss (22.6 vs. 8% in stages one and two). Conclusion: Using precision medicine, we have demonstrated clustering of CLTI patients that can be used toward a robust staging system. We provide empiric evidence for PLAN and detail about how changes in each variable affect survival and amputation-free survival.

The impact of phased university reopenings on mitigating the spread of COVID-19: a modeling study.

BACKGROUND: Several American universities have experienced COVID-19 outbreaks, risking the health of their students, employees, and local communities. Such large outbreaks have drained university resources and forced several institutions to shift to remote learning and send students home, further contributing to community disease spread. Many of these outbreaks can be attributed to the large numbers of active infections returning to campus, alongside high-density social events that typically take place at the semester start. In the absence of effective mitigation measures (e.g., high-frequency testing), a phased return of students to campus is a practical intervention to minimize the student population size and density early in the semester, reduce outbreaks, preserve institutional resources, and ultimately help mitigate disease spread in communities. METHODS: We develop dynamic compartmental SARS-CoV-2 transmission models to assess the impact of a phased reopening, in conjunction with pre-arrival testing, on minimizing on-campus outbreaks and preserving university resources (measured by isolation bed capacity). We assumed an on-campus population of N = 7500, 40% of infected students require isolation, 10 day isolation period, pre-arrival testing removes 90% of incoming infections, and that phased reopening returns one-third of the student population to campus each month. We vary the disease reproductive number (Rt) between 1.5 and 3.5 to represent the effectiveness of alternative mitigation strategies throughout the semester. RESULTS: Compared to pre-arrival testing only or neither intervention, phased reopening with pre-arrival testing reduced peak active infections by 3 and 22% (Rt = 1.5), 22 and 29% (Rt = 2.5), 41 and 45% (Rt = 3.5), and 54 and 58% (improving Rt), respectively. Required isolation bed capacity decreased between 20 and 57% for values of Rt ≥ 2.5. CONCLUSION: Unless highly effective mitigation measures are in place, a reopening with pre-arrival testing substantially reduces peak number of active infections throughout the semester and preserves university resources compared to the simultaneous return of all students to campus. Phased reopenings allow institutions to ensure sufficient resources are in place, improve disease mitigation strategies, or if needed, preemptively move online before the return of additional students to campus, thus preventing unnecessary harm to students, institutional faculty and staff, and local communities.