Current concepts in clinical features and diagnosis of thoracic outlet syndrome.

The diagnosis and clinical features of thoracic outlet syndrome have long confounded clinicians, owing to heterogeneity in symptom presentation and many overlapping competing diagnoses that are "more common." Despite the advent and prevalence of high-resolution imaging, along with the increasing awareness of the syndrome itself, misdiagnoses and untimely diagnoses can result in significant patient morbidity. The authors aimed to summarize the current concepts in the clinical features and diagnosis of thoracic outlet syndrome.

Current outcomes following upper and lower extremity arterial trauma from the National Trauma Data Bank.

OBJECTIVE: The modern treatments of trauma have changed in recent years. We aim to evaluate the factors associated with limb salvage and mortality after extremity arterial trauma, especially with respect to the type of conduit used in revascularization. METHODS: The National Trauma Data Bank was queried to identify patients with upper and lower extremity (UE and LE) arterial injuries between 2016 and 2020. The patients were stratified by the types of arterial repair. The primary outcome was in-hospital mortality. RESULTS: 8780 patients were found with 5054 (58%) UE and 3726 (42%) LE injuries. Eighty-three percent were men, and the mean age was 34 ± 15 years. Penetrating mechanism was the predominant mode of injury in both UEs and LEs (73% and 67%, respectively) with a mean injury severity score of 14 ± 8. For UEs, the majority underwent primary repair (67%, P < .001), whereas the remainder received either a bypass (20%) or interposition graft (12%). However, LEs were more likely to receive a bypass (52%, P < .00001) than primary repair or interposition graft (34% and 14%, respectively). Compared with the extremely low rates of amputation and mortality among UE patients (2% for both), LE injuries were more likely to result in both amputation (10%, P < .001) and death (6%, P < .001). Notably, compared with primary repair, the use of a prosthetic conduit was associated with a 6.7-fold increase in the risk of amputation in UE and a 2.4-fold increase in LE (P < .0001 for both). Synthetic bypasses were associated with a nearly 3-fold increase in return to the operating room (OR) in UE bypasses (P < .05) and a 2.4-fold increase in return to the OR in LE bypasses (P < .0001). CONCLUSIONS: In recent years, most extremity vascular trauma was due to penetrating injury with a substantial burden of morbidity and mortality. However, both limb salvage rates and survival rates have remained high. Overall, LE injuries more often led to amputation and mortality than UE injuries. The most frequently used bypass conduit was vein, which was associated with less risk of unplanned return to the OR and limb loss, corroborating current practice guidelines for extremity arterial trauma.

Five-year outcomes of fenestrated and branched endovascular repair of complex aortic aneurysms based on aneurysm extent.

OBJECTIVE: The aim of this study was to evaluate the 5-year outcomes of fenestrated/branched endovascular aortic repair (F/BEVAR) for the treatment of complex aortic aneurysms stratified by the aneurysm extent. METHODS: Patients with the diagnosis of complex aortic aneurysm, who underwent F/BEVAR at a single center were included in this study and retrospectively analyzed. The cohort was divided according to the aneurysm extent, comparing group 1 (types I-III thoracoabdominal aneurysms [TAAAs]), group 2 (type IV TAAAs), and group 3 (juxtarenal [JRAAs], pararenal [PRAAs], or paravisceral [PVAAs] aortic aneurysms). The primary endpoints were 30-day and 5-year survival. The secondary endpoints were technical success, occurrence of spinal cord ischemia, primary patency of the visceral arteries, freedom from target vessel instability, and secondary interventions. RESULTS: Of 436 patients who underwent F/BEVAR between July 2012 and May 2023, 131 presented with types I to III TAAAs, 69 with type IV TAAAs, and 236 with JRAAs, PRAAs, or PVAAs. All cases were treated under a physician-sponsored investigational device exemption protocol with a patient-specific company-manufactured or off-the-shelf device. Group 1 had significantly younger patients than group 2 or 3 respectively (69.6 ± 8.7 vs 72.4 ± 7.1 vs 73.2 ± 7.3 years; P < .001) and had a higher percentage of females (50.4% vs 21.7% vs 17.8%; P < .001). Prior history of aortic dissection was significantly more common among patients in group 1 (26% vs 1.4% vs 0.9%; P < .001), and mean aneurysm diameter was larger in group 1 (64.5 vs 60.7 vs 63.2 mm; P = .033). Comorbidities were similar between groups, except for coronary artery disease (P < .001) and tobacco use (P = .003), which were less prevalent in group 1. Technical success was similar in the three groups (98.5% vs 98.6% vs 98.7%; P > .99). The 30-day mortality was 4.5%, 1.4%, and 0.4%, in groups 1, 2, and 3, respectively, and was significantly higher in group 1 when compared with group 3 (P = .01). The incidence of spinal cord ischemia was significantly higher in group 1 compared with group 3 (5.3% vs 4.3% vs 0.4%; P = .004). The 5-year survival was significantly higher in group 3 when compared with group 1 (P = .01). Freedom from secondary intervention was significantly higher in group 3 when compared with group 1 (P = .003). At 5 years, there was no significant difference in freedom from target vessel instability between groups or primary patency in the 1652 target vessels examined. CONCLUSIONS: Larger aneurysm extent was associated with lower 5-year survival, higher 30-day mortality, incidence of secondary interventions, and spinal cord ischemia. The prevalence of secondary interventions in all groups makes meticulous follow-up paramount in patients with complex aortic aneurysm treated with F/BEVAR.

Individualized treatment rule characterization via a value function surrogate.

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.

Peripheral Vascular Disease.

Peripheral artery disease is most often caused by atherosclerosis. Arterial insufficiency from atherosclerotic blockages in the limbs can impair walking distance and put patients with severe disease at risk of limb loss. Management of the disease centers around early diagnosis, supervised exercise therapy and lifestyle modification, optimizing medical care (with the goal of reducing fatal cardiac and cerebrovascular events), and revascularization.

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.

Balancing evidence-based care with patient-centered individualized care.

Weak evidence, when manifested in clinical guidelines, can translate into biased vascular care. In vascular surgery, we have few randomized controlled trials with appropriate representation of females and persons of color, so generalizability of trial results can be problematic. Physicians are required to balance evidenced-based care (which is only as good as the underlying evidence) with personalized treatment recommendations that are often based on demographics, social circumstances, and/or existing therapeutic relationships. Biases, whether implicit or explicit, have an oversized effect on treatment decisions, and patient outcomes. In this commentary, we propose three principles to strengthen the vascular surgery evidence foundation and patient-centered decision-making going forward: (1) generating evidence designed for individualized care, (2) constructing clinical guidelines that are context specific and complexity aware, and (3) strengthening the training and support for surgeons to deliver patient-centered individualized care.

Medial arterial calcification score is associated with increased risk of major limb amputation.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Differential impact of missed initial wound clinic visit on 6-month wound healing by race/ethnicity among patients with chronic limb-threatening ischemia.

Chronic limb-threatening ischemia (CLTI) is associated with significant morbidity, including major limb amputation, and mortality. Healing ischemic wounds is necessary to optimise vascular outcomes and can be facilitated by dedicated appointments at a wound clinic. This study aimed to estimate the association between successful wound care initiation and 6-month wound healing, with specific attention to differences by race/ethnicity. This retrospective study included 398 patients with CLTI and at least one ischaemic wound who scheduled an appointment at our wound clinic between January 2015 and July 2020. The exposure was the completion status of patients' first scheduled wound care appointment (complete/not complete) and the primary outcome was 6-month wound healing (healed/not healed). The analysis focused on how this association was modified by race/ethnicity. We used Aalen-Johansen estimators to produce cumulative incidence curves and calculated risk ratios within strata of race/ethnicity. The final adjustment set included age, revascularization, and initial wound size. Patients had a mean age of 67 ± 14 years, were 41% female, 46% non-White and had 517 total wounds. In the overall cohort, 70% of patients completed their first visit and 34% of wounds healed within 6-months. There was no significant difference in 6-month healing based on first visit completion status for White/non-Hispanic individuals (RR [95% CI] = 1.18 [0.91, 1.45]; p-value = 0.130), while non-White individuals were roughly 3 times more likely to heal their wounds if they completed their first appointment (RR [95% CI] = 2.89 [2.66, 3.11]; p-value < 0.001). In conclusion, non-White patients were approximately three times more likely to heal their wound in 6 months if they completed their first scheduled wound care appointment while White/non-Hispanic individuals' risk of healing was similar regardless of first visit completion status. Future efforts should focus on providing additional resources to ensure minority groups with wounds have the support they need to access and successfully initiate wound care.

Gender disparities in patients with aortoiliac disease requiring open operative intervention.

OBJECTIVE: Peripheral artery disease is known to affect males and females in different proportions. Disparate surgical outcomes have been quantified after endovascular aortic aneurysm repair, arteriovenous fistula creation, and treatment of critical limb ischemia. The aim of this study is to objectively quantify the sex differences in outcomes in patients undergoing open surgical intervention for aortoiliac occlusive disease. METHODS: Patients were identified in the aortoiliac occlusive disease Vascular Quality Initiative database who underwent aorto-bifemoral bypass or aortic thromboendarterectomy as determined by Current Procedural Terminology codes between 2012 and 2019. Patients with a minimum of 1-year follow-up were included. Risk differences (RDs) by sex were calculated using a binomial regression model in 30-day and 1-year incidence of mortality and limb salvage. Additionally, incidence of surgical complications including prolonged length of stay (>10 days), reoperation, and change in renal function (>0.5 mg/dl rise from baseline), were recorded. Inverse probability weighting was used to standardize demographic and medical history characteristics. Multivariate logistic regression models were employed to conduct analyses of the before mentioned clinical outcomes, controlling for known confounders. RESULTS: Of 16,218 eligible patients from the VQI data during the study period, 6538 (40.3%) were female. The mean age, body mass index, and race were not statistically different between sexes. Although there was no statistically significant difference detected in mortality between males and females at 30 days postoperatively, females had an increased crude 1-year mortality with an RD of 0.014 (95% confidence interval, 0.01-0.02; P value < .001. Males had a higher rate of a postoperative change in renal function with an RD of -0.02 (95% confidence interval, -0.03 to -0.01; P < .001). CONCLUSIONS: Although there was no sex-based mortality difference at 30 days, there was a statistically significant increase in mortality in females after open aortoiliac intervention at 1 year based on our weighted model. Male patients are statistically significantly more likely to have a decline in renal function after their procedures when compared with females. Postoperative complications including prolonged hospital stay, reoperation, and wound disruption were similar among the sexes, as was limb preservation rates at 1 year. Further studies should focus on elucidating the underlying factors contributing to sex-based differences in clinical outcomes following aortoiliac interventions.

Outcome Analysis Comparing Asymptomatic Juxtarenal Aortic Aneurysms Treated with Custom-Manufactured Fenestrated-Branched Devices and the "Off-The-Shelf" Zenith p-Branch Device.

BACKGROUND: Numerous endovascular options have been used for the repair of juxtarenal aortic aneurysms (JRAAs) over the last 15 years. This study aims to compare the performance between the Zenith p-branch device and custom-manufactured fenestrated-branched devices (CMD) for the treatment of asymptomatic JRAA. METHODS: A single-center retrospective analysis of prospectively collected data was performed. Patients with a diagnosis of JRAA submitted to endovascular repair between July 2012 and November 2021 were included in the study, being divided into 2 groups: CMD and Zenith p-branch. The following variables were analyzed: preoperative information: demographics, comorbidities, and maximum aneurysm diameter; procedural data: contrast volume, fluoroscopy time, radiation dose, estimated blood loss, and technical success; and postoperative data: 30-day mortality, duration of intensive care unit and hospital stay, major adverse events, secondary interventions, target vessel instability, and long-term survival. RESULTS: From a total of 373 physician-sponsored investigational device exemption (Cook Medical devices) cases performed at our institution, 102 patients presented the diagnosis of JRAA. Of these, 14 patients were treated with the p-branch device (13.7%) and 88 (86.3%) with a CMD. Both groups presented similar demographic composition and maximum aneurysm diameter. All devices were successfully deployed, with no type I or III endoleaks observed at procedure completion. The contrast volume (P = 0.023) and radiation dose (P = 0.001) were significantly higher in the p-branch group. No significant difference was observed between the groups for the remaining intraoperative data. No paraplegia or ischemic colitis has been observed during the first 30 days after the surgical procedures. There was no 30-day mortality in either group. One major cardiac adverse event was registered in the CMD group. Early outcomes were similar in both groups. No significant difference was found between the groups with respect to the presence of type I or III endoleaks during the follow-up. From a total of 313 target vessels stented in the CMD group (mean of 3.55 per patient) and 56 in the p-branch group (mean of 4 per patient), 4.79% and 5.35% presented instability, respectively, with no difference observed between the groups (P = 0.743). Secondary interventions were required in 36.4% of the CMD cases and 50% of the p-branch group, but this was not statistically different (P = 0.382). In the p-branch cohort, 2 of 7 reinterventions (28.5%) were target vessel-related and in the CMD group, 10 of 32 secondary interventions (31.2%) were target vessel-related. CONCLUSIONS: Comparable perioperative outcomes were obtained when appropriately selected patients were treated with either the off-the-shelf p-branch or CMD for JRAA. The long-term target vessel instability does not appear impacted by the presence of pivot fenestrations in comparison to other target vessel configurations. Given these outcomes, delay in CMD production time should be considered when treating patients with large juxtarenal aneurysms.

A framework for perioperative care for lower extremity vascular bypasses: A Consensus Statement by the Enhanced Recovery after Surgery (ERAS®) Society and Society for Vascular Surgery.

The Society for Vascular Surgery and the Enhanced Recovery After Surgery (ERAS) Society formally collaborated and elected an international, multi-disciplinary panel of experts to review the literature and provide evidence-based suggestions for coordinated perioperative care for patients undergoing infrainguinal bypass surgery for peripheral artery disease. Structured around the ERAS core elements, 26 suggestions were made and organized into preadmission, preoperative, intraoperative, and postoperative sections.

Depression in Patients with Peripheral Artery Disease: An Underdiagnosis with Increased Mortality.

BACKGROUND: 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. METHODS: 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 χ2 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. RESULTS: 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. CONCLUSIONS: 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 Use of Sequential Surveys to Shorten Implementation Time for Healthcare System-Level Enhanced Recovery After Surgery (ERAS) Pathways.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways improve healthcare quality, safety, and cost-effectiveness. We hypothesized that the RAND Method (a hybrid Delphi approach), involving anonymous sequential surveys and face-to-face meetings, would allow for more rapid agreement and initiation of new ERAS pathways. METHODS: Using the ERAS Society guidelines for cesarean section as a baseline, our institution's ERAS Leadership Team (ELT) compiled published literature and institutional practices to design a 32-component survey that was sent to obstetricians, nurse midwives, anesthesiologists, pharmacists, and nurses. Components that did not reach 90% consensus were included in a second survey the following week, and meetings were held to review results. At the conclusion of this process, time to agreement was retrospectively compared to the colorectal ERAS pathway process at this institution. RESULTS: ERAS pathway components were compiled and reviewed by 121 stakeholders at 7 hospitals using iterative surveys with review meetings over a 13-week period. Survey response rates were 61% and 50% in the initial and follow-up surveys, respectively. There was agreement on 28/32 and 32/32 items on the initial and follow-up surveys. Using the RAND Method, time to agreement decreased by 54.1% (24 vs 13 weeks) compared to prior system-wide efforts to standardize the colorectal surgery ERAS pathway. DISCUSSION: With rapidly expanding healthcare systems, effective methods to gain consensus and adopt ERAS pathways are critical to implementation of ERAS guidelines. We demonstrate that the RAND Method allows for a transparent and efficient means of agreement across a diverse group of clinicians practicing in several settings.

Iliac vein recanalisation and stenting accelerate healing of venous leg ulcers associated with severe venous outflow obstruction.

Obstruction involving the iliac veins and/or inferior vena cava is highly comorbid in patients with chronic venous leg ulcers and is a barrier to healing. Intervention with venous stenting is recommended to promote wound healing; however, there is limited data to quantify the effects of venous outflow restoration on wound healing. We retrospectively identified patients with venous ulcers and comorbid venous outflow obstruction. Data regarding demographics, wound size, degree of obstruction, interventions, wound healing and recurrence were collected. Intervention was performed when possible and patients were grouped based on whether or not the venous outflow was reopened successfully and maintained for at least 1 year. Outcomes, including time to wound healing, wound recurrence, stent patency and ulcer-free time, were measured. Patients who maintained a patent venous outflow tract experienced higher rates of wound healing (79.3%) compared to those with persistent outflow obstruction (22.6%) at 12 months (p < 0.001). Ulcer-free time for the first year was also greater with patent venous outflow (7.6 ± 4.4 months versus 1.8 ± 3.0 months, p < 0.0025). Patients with severe obstruction of the venous outflow tract experience poor healing of VLUs despite appropriate wound care. Healing time is improved and ulcer-free time increased after venous intervention with stenting to eliminate obstruction.

Incidence of venous thromboembolism in patients with peripheral arterial disease after endovascular intervention.

OBJECTIVE: Venous thromboembolism (VTE) is a well-known postoperative complication; however, the incidence of VTE after peripheral vascular intervention (PVI) has not been well described. Despite the minimally invasive nature of these procedures, the patients undergoing PVI have significant risk factors for the development of VTE. In the present study, our objective was to describe the short-term incidence of VTE after PVI, identify differences between sexes, and examine the periprocedural antiplatelet and anticoagulation regimens. METHODS: We identified adults (age >66 years) who had undergone PVI from January 1, 2008 to September 30, 2015 from the inpatient Medicare claims data. The patients were followed for 365 days after the procedure. VTE events during follow-up were identified using the International Classification of Diseases, 9th revision, diagnosis codes. The covariate-standardized 30- and 90-day cumulative incidence of VTE events, overall and stratified by sex, were estimated using Aalen-Johansen estimators, accounting for death as a competing risk. Differences in sex between females and males were identified using Gray's test. Any antiplatelet or anticoagulant prescription fill was defined as any fill from 14 days before the endovascular intervention through the date of the VTE event. Persistence with antiplatelet and anticoagulant therapy was assessed by creating daily logs of antiplatelet and anticoagulant coverage using the dispensing dates and days of supply. Over-the-counter medications (ie, aspirin) were not evaluated. RESULTS: We identified 31,593 qualifying patients with a mean age of 76.8 ± 7.4 years. Of the 31,593 patients, 46% were male, and 12% had a history of VTE. After the procedure, deep vein thrombosis (DVT) was a commonly diagnosed complication (3.8% and 4.8% at 30 and 90 days, respectively). The cumulative incidence of pulmonary embolism was 0.9% and 1.2% at 30 and 90 days after the procedure, respectively. Throughout the 90-day postoperative period, females had had a slightly increased risk of DVT compared with males (30-day risk difference, 0.007; P < .01; 90-day risk difference, 0.008; P = .02). We found no sex-based differences in the risk of pulmonary embolism. Of the patients who had developed VTE at 90 days, 970 (55%) had had no prescription fill for an antiplatelet or anticoagulant. Assuming all the patients had been taking aspirin, only 15% of the patients who had developed VTE had been taking prescribed dual antiplatelet medication persistently after PVI. In addition, among the patients who had developed VTE at 90 days, females were less likely to have had a prescription fill for an anticoagulant. CONCLUSIONS: The findings from our study have demonstrated that the incidence of VTE after PVI is high, with an increased risk of deep vein thrombosis for females. We also found that females were less likely to have been prescribed an anticoagulant after PVI. Future studies are needed to characterize the variables associated with an increased risk of VTE after PVI and to identify strategies to increase dual antiplatelet therapy or anticoagulant prescription adherence to reduce the risk of VTE.

Central concepts for randomized controlled trials and other emerging trial designs.

Randomized controlled trials (RCTs) are widely considered to provide the highest-quality evidence for the comparative efficacy and safety of competing clinical strategies. The strength of using RCTs for causal inference is derived from random treatment assignment and prospective data collection. Randomization eliminates confounding at the time of treatment group assignment, achieving exchangeability of the baseline study groups, such that they are the same, on average, except for the study intervention. Prospective data collection helps ensure that eligibility assessment, treatment assignment, and the start of follow-up are aligned temporally. Temporal alignment prevents biases that are common in observational research (eg, immortal time bias). In ideal settings, the results of an RCT provide the average causal effect of the intervention on the selected outcomes in the study population. Although observational research can estimate similar causal effects, observational designs require more assumptions and more advanced analytic frameworks than an RCT designed to answer the same question. Emerging trial designs, also discussed here, seek to address certain limitations of traditional RCT designs. The purpose of this review was to provide a broad overview of the central concepts in RCT design, implementation, conduct, and data analysis.

Analysis of wound healing time and wound-free period in patients with chronic limb-threatening ischemia treated with and without revascularization.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.