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Objective: The recent publication of randomized trials comparing open bypass surgery to endovascular therapy in patients with chronic limb-threatening ischemia, namely, Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) and Bypass versus Angioplasty in Severe Ischaemia of the Leg-2 (BASIL-2), has resulted in potentially contradictory findings. The trials differed significantly with respect to anatomical disease patterns and primary end points. We performed an analysis of patients in BEST-CLI with significant infrapopliteal disease undergoing open tibial bypass or endovascular tibial interventions to formulate a relevant comparator with the outcomes reported from BASIL-2., Methods: The study population consisted of patients in BEST-CLI with adequate single segment saphenous vein conduit randomized to open bypass or endovascular intervention (cohort 1) who additionally had significant infrapopliteal disease and underwent tibial level intervention. The primary outcome was major adverse limb event (MALE) or all-cause death. MALE included any major limb amputation or major reintervention. Outcomes were evaluated using Cox proportional regression models., Results: The analyzed subgroup included a total of 665 patients with 326 in the open tibial bypass group and 339 in the tibial endovascular intervention group. The primary outcome of MALE or all-cause death at 3 years was significantly lower in the surgical group at 48.5% compared with 56.7% in the endovascular group (P = .0018). Mortality was similar between groups (35.5% open vs 35.8% endovascular; P = .94), whereas MALE events were lower in the surgical group (23.3% vs 35.0%; P<.0001). This difference included a lower rate of major reinterventions in the surgical group (10.9%) compared with the endovascular group (20.2%; P = .0006). Freedom from above ankle amputation or all-cause death was similar between treatment arms at 43.6% in the surgical group compared with 45.3% the endovascular group (P = .30); however, there were fewer above ankle amputations in the surgical group (13.5%) compared with the endovascular group (19.3%; P = .0205). Perioperative (30-day) death rates were similar between treatment groups (2.5% open vs 2.4% endovascular; P = .93), as was 30-day major adverse cardiovascular events (5.3% open vs 2.7% endovascular; P = .12)., Conclusions: Among patients with suitable single segment great saphenous vein who underwent infrapopliteal revascularization for chronic limb-threatening ischemia, open bypass surgery was associated with a lower incidence of MALE or death and fewer major amputation compared with endovascular intervention. Amputation-free survival was similar between the groups. Further investigations into differences in comorbidities, anatomical extent, and lesion complexity are needed to explain differences between the BEST-CLI and BASIL-2 reported outcomes., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Female patients are less likely to be diagnosed with and treated for peripheral artery disease. When treated, there are also reported sex disparities in short- and long-term outcomes. We designed this study to compare outcomes after open and endovascular revascularization in the Best Endovascular vs best Surgical Therapy in patients with Critical Limb Ischemia (BEST-CLI) trial between females and males, and to examine outcomes of each revascularization type in an all-female cohort., Methods: In a secondary analysis of cohorts 1 and 2 of the BEST-CLI Trial, patients with chronic limb-threatening ischemia (CLTI) undergoing open surgical bypass (with or without adequate conduit) and endovascular therapy were stratified by sex. In addition, in a female-only cohort, we evaluated differences in outcomes between treatment arm (combined all bypasses from cohorts 1 and 2 and compared with all endovascular treatment in cohorts 1 and 2). Outcomes included major amputation, reintervention, major adverse limb event (MALE, a composite of major amputation and reintervention), all-cause death, and composite outcome of MALE or all-cause death. Univariable and adjusted Cox regressions were used to assess outcome between males and females. Similar methods were used to assess differences in outcomes between treatment arm in females., Results: Among 1830 patients, females were significantly underrepresented, comprising only 28% (n = 519) of the BEST-CLI cohort. Overall, the characteristics of females enrolled in the trial had some differences compared with males: females were more likely to have rest pain alone (72% vs 60%; P < .0001) and when presenting with an ischemic wound, were less likely to have a wound infection (38% vs 47%; P = .01). Females were less likely to have an adequate single-segment greater saphenous vein (SSGSV) available (82% vs 89%; P = .01). Controlled for baseline clinical factors, at 1 year, females had significantly lower rates of major limb amputation compared with males (hazard ratio [HR], 0.70; P = .023), which drove better amputation- and MALE-free survival rates. All-cause death at 1 year was not statistically different between sexes (11.8% vs 11.2%; P = .286). In the all-female cohort, results paralleled the overall trial; open surgical bypass (with any conduit) had significantly better outcomes compared with endovascular therapy. Specifically, among females undergoing endovascular therapy, the rate of major reintervention was particularly high compared with females undergoing open surgical bypass (24.8% vs 10.5%; P < .001)., Conclusions: Despite being underrepresented in BEST-CLI, the primary results of the trial, namely, improved MALE-free survival with open surgical bypass with SSGSV, were mirrored in the all-female subset. Female patients enrolled in BEST-CLI had better amputation-free survival at 1 year compared with male patients. These findings suggest that in treating female patients with CLTI considered appropriate for both open and endovascular revascularization, surgical bypass with optimal conduit is the preferred treatment option and can potentially ameliorate poor limb preservation outcomes associated with sex., Competing Interests: Disclosures K.M. reports consultant for Medtronic Inc, and Vascular Technologies Inc; and research funding from NovoNordisk Foundation. K.R. reports consultant or member of a scientific advisory board for the following entities: Abbott Vascular, Althea Medical, Angiodynamics, Auxetics, Becton-Dickinson, Boston Scientific, Contego, Crossliner, Innova Vascular, Inspire MD, Janssen/Johnson and Johnson, Magneto, Mayo Clinic, MedAlliance, Medtronic, Neptune Medical, Penumbra, Philips, Surmodics, Terumo, Thrombolex, Truvic, Vasorum, and Vumedi; owns equity or stock options in the following entities: Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Crossliner, Cruzar Systems, Endospan, Imperative Care/Truvic, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Prosomnus, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vasorum, and Vumedi; and K.R. or his institution (on his behalf) receive research grants from the following entities: National Institutes of Health, Abiomed, Boston Scientific, Novo Nordisk Foundation, Penumbra, and Gettinge-Atrium; and serves as a member of the Board of Directors of the following organization: The National PERT Consortium. M.M. reports research grant from NovoNordisk Foundation; and advisory board for Janssen. A.F. reports grants from the Novo Nordisk Foundation; consultant for Sanifit, LeMaitre, and BioGenCell; and advisory board for Dialysis-X and iThera Medical. K.C. reports consultant for W.L. Gore & Associates and Venostent; and research support from Inari Medical, Vesper Medical, BD, and Johnson & Johnson. K.G. reports advisory board for Boston Scientific., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Single segment great saphenous vein (SSGSV) traditionally has been considered the gold standard conduit for infrainguinal bypass. There are data supporting similar outcomes with prosthetic femoral-popliteal bypass. Moreover, some investigators have advocated for prosthetic conduit for femoral tibial bypass when GSV is inadequate or unavailable. We sought to evaluate long-term outcomes of infrainguinal bypass based on conduit type for treating chronic limb-threatening ischemia (CLTI)., Methods: Data from the Best Endovascular vs Best Surgical Therapy of Patients with CLTI multicenter, prospective, randomized controlled trial, comparing infrainguinal bypass with endovascular therapy in patients with CLTI, were evaluated. In this as-treated analysis, we compared outcomes of infrainguinal bypass using prosthetic, alternative autogenous vein (AAV), and cryopreserved vein (Cryo) with SSGSV bypass. Kaplan-Meier and multivariable analyses were performed to examine the associations of conduit type with major adverse limb events (MALE), reinterventions, above-ankle amputations, and all-cause death rates., Results: In total, 784 bypasses were analyzed (120 prosthetic, 33 AAV, 21 Cryo, AND 610 SSGSV). For prosthetic and SSGSV, the distribution was 357 femoropopliteal (93 prosthetic and 264 GSV) and 373 infrapopliteal (27 prosthetic and 346 GSV). The mean age for the overall cohort was 67.1 years; 27.4% were female, 29.9% were non-White, and 11.5% were of Hispanic ethnicity. Patients undergoing prosthetic bypass were older (69.2 years vs 66.7 years); more likely to have chronic obstructive pulmonary disease (22.5% vs 14.0%), prior coronary artery bypass grafting (88.9% vs 66.5%), and prior stroke (23.3% vs 14%); but less often were of Hispanic ethnicity (5.8% vs 12.6%) and had diabetes (59.2% vs 71.3%) (P < .05 for all). For femoropopliteal bypass, use of prosthetic conduit was associated with increased major reinterventions at 3 years overall (19.0% vs 11.5%; P = .06) and on risk-adjusted analysis (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.09-4.2; P = .028). No significant differences in MALE or death, above-ankle amputation, or death were observed. Outcomes were similar for bypasses to above-knee popliteal targets and below-knee popliteal targets. For infrapopliteal bypass, the use of a prosthetic conduit was associated with increased major reintervention (25.3% vs 10.3%; P = .005), death (68.6% vs 34.8%; P < .001), and MALE or death (90.0% vs 48.1%; P < .001) at 3 years. After risk adjustment, infrapopliteal bypass with prosthetic conduit was associated with higher major reintervention (HR, 4.14; 95% CI, 1.36-12.6; P = .012), above-ankle amputation (HR, 4.64; 95% CI, 1.59-13.5; P = .005), death (HR, 2.96; 95% CI, 1.4-6.2; P = .004), and MALE or death (HR, 3.59; 95% CI, 1.64-7.86; P = .001) compared with bypass with SSGSV. Overall, AAV had similar outcomes at 3 years as SSGSV; however, Cryo had significantly higher above-ankle amputation (50.0% vs 12.8%) (HR, 4.2; 95% CI, 1.68-10.5; P = .002), major reintervention (41.9% vs 10.7%) (HR, 3.12; 95% CI, 1.18-8.22; P = .02), and MALE/death (88.8% vs 37.8%) (HR, 2.96; 95% CI, 1.43-6.14; P = .004)., Conclusions: The use of a prosthetic conduit in infrainguinal bypass is associated with inferior outcomes compared with bypass using SSGSV, particularly for bypass to infrapopliteal targets. Cryo grafts were infrequent and also demonstrated inferior outcomes. SSGSV remains the preferred conduit of choice for infrainguinal bypass., Competing Interests: Disclosures J.S. reports educational grants from W. L. Gore & Associates and BD. M.M. is a member of the scientific advisory board for Janssen. M.C. is on the Abbott Vascular DSMB. K.R. is a member of the Scientific Advisory Board or Consultant for Abbott Vascular, Access Vascular, Boston Scientific-BTG, Volcano-Philips, Surmodics, Cruzar Systems, Magneto, Summa Therapeutics, and University of Maryland; an unpaid member of the Scientific Advisory Board of Thrombolex, Inc; received grants from NIH and Boston Scientific; has equity from Access Vascular, Accolade, Contego, Endospan, Embolitech, Eximo, JanaCare, PQ Bypass, Primacea, MD Insider, Shockwave, Silk Road, Summa Therapeutics, Cruzar Systems, Capture, Vascular, Magneto, Micell, and Valcare; and is a board member of VIVA Physicians, a not-for-profit 501c3, and National PERT ConsortiumTM, a not for profit 501c3. A.F. is a grant recipient of the Novo Nordisk Foundation; a consultant for Sanifit, LeMaitre, and BioGenCell; and on the advisory board for Dialysis-X and iThera Medical., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Cardiovascular complications after revascularization to treat chronic limb-threatening ischemia (CLTI) are a major concern that guides treatment. Our goal was to assess periprocedural cardiac and vascular serious adverse events (SAEs) in the Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial., Methods: BEST-CLI was a prospective randomized trial comparing surgical (OPEN) and endovascular (ENDO) revascularization for patients with CLTI. Thirty-day SAEs, classified as cardiac or vascular, were analyzed. Adverse events are defined as serious when they affect safety in the trial, require prolonged hospitalization, result in significant disability or incapacitation, are life-threatening, or result in death. Interventions were analyzed in a per protocol fashion., Results: In the BEST-CLI trial, 850 OPEN and 896 ENDO interventions were evaluated. Forty (4.7%) and 34 (3.8%) patients experienced at least one cardiac SAE after OPEN and ENDO intervention, respectively (P = .35). Overall, there were 53 cardiac SAEs (0.06 per patient) after OPEN and 40 (0.045 per patient) after ENDO interventions. Cardiac SAEs in the OPEN arm were classified as related to ischemia (50.9%), arrhythmias (17%), heart failure (15.1%), arrest (13.2%), and heart block (3.8%); in the ENDO arm, they were classified as ischemia (47.5%), heart failure (17.5%), arrhythmias (15%), arrest (15%), and heart block (5%). Approximately half of SAEs were classified as severe for both OPEN and ENDO. SAEs were definitely or probably related to the procedure in 30.2% and 25% in the OPEN and ENDO arms, respectively (P = .2). Vascular SAEs occurred in 58 (6.8%) and 86 (9.6%) of patients after OPEN and ENDO revascularization, respectively (P = .19). In total, there were 59 (0.07 per patient) and 87 (0.097 per patient) vascular SAEs after OPEN and ENDO procedures. Vascular SAEs in the OPEN arm were classified as distal ischemia/infection (44.1%), bleeding (16.9%), occlusive (15.3%), thromboembolic (15.3%), cerebrovascular (5.1%), and other (3.4%); in the ENDO arm, they were distal ischemia/infection (40.2%), occlusive (31%), bleeding (12.6%), thromboembolic (8%), cerebrovascular (1.1%), and other (4.6%). SAEs were classified as severe for OPEN in 45.8% and ENDO in 46%. SAEs were definitely or probably related to the procedure in 23.7% and 35.6% in the OPEN and ENDO arms (P = .35), respectively., Conclusions: Patients undergoing OPEN and ENDO revascularization experienced similar degrees of cardiac and vascular SAEs. The majority were not related to the index intervention, but approximately half were severe., Competing Interests: Disclosures J.J.S. reports education grants from WL Gore and BD paid to Boston University. A.F. is a consultant for Sanifit. M.T.M. has served on the scientific advisory board for Janssen. M.S.C. is on the Data Safety Monitoring Board for Abbott Vascular. K.R. is a member of the scientific advisory board or a consultant for Abbott Vascular, Access Vascular, Boston Scientific-BTG, Volcano-Philips, Surmodics, Cruzar Systems, Magneto, Summa Therapeutics, and University of Maryland; is an unpaid member of the scientific advisory board of Thrombolex, Inc; received grants from the National Institutes of Health and Boston Scientific; has equity from Access Vascular, Accolade, Contego, Endospan, Embolitech, Eximo, JanaCare, PQ Bypass, Primacea, MD Insider, Shockwave, Silk Road, Summa Therapeutics, Cruzar Systems, Capture Vascular, Magneto, Micell, and Valcare; and is a board member of VIVA Physicians, a not-for-profit 501c3, and National PERT Consortium, a not-for-profit 501c3. The remaining authors report no conflicts., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Sustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial., Methods: As planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created., Results: In cohort 1, there was a significant difference in time to clinical failure (log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2., Conclusions: Durable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms., Competing Interests: Disclosures M.T.M. is the advisor for Janssen. A.F. grants from Novo Nordisk Foundation; is a consultant for Sanifit, LeMaitre, and BioGenCell; and is on the advisor board of Dialysis-X and iThera Medical. L.C.C. is a consulting speaker for Cook Medical. P.A.S. is a consultant for Medtronic, Boston Scientific, Philips, Silk Road, Surmodics, Cagent, and Limflow. B.M.H. reports research grants (site PI for clinical trials, no compensation) from Boston Scientific and NIH/NHLBI. M.D.D. is a consultant for Cook Medical, W.L. Gore, and Boston Scientific. K.R. receives income as a consultant or member of a scientific advisory board for the following entities: Abbott Vascular, Althea Medical, Angiodynamics, Auxetics, Becton-Dickinson, Boston Scientific, Contego, Crossliner, Innova Vascular, Inspire MD, Janssen/Johnson and Johnson, Magneto, Mayo Clinic, MedAlliance, Medtronic, Neptune Medical, Penumbra, Philips, Surmodics, Terumo, Thrombolex, Truvic, Vasorum, and Vumedi; and owns equity or stock options in the following entities: Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Crossliner, Cruzar Systems, Endospan, Imperative Care/Truvic, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Prosomnus, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vasorum, and Vumedi. K.R. or his institution (on his behalf) receives research grants from the following entities: NIH, Abiomed, Boston Scientific, Novo Nordisk Foundation, Penumbra, and Gettinge-Atrium. He serves as a member of the Board of Directors of the following organization: The National PERT Consortium. M.S.C. has a relationship with Abbott Vascular DSMB. The remaining authors report no conflicts., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In the BEST-CLI trial (Best Endovascular Versus Best Surgical Therapy for Patients With Chronic Limb-Threatening Ischemia), a prespecified secondary objective was to assess the effects of revascularization strategy on health-related quality of life (HRQoL)., Methods: Patients with chronic limb-threatening ischemia were randomized to surgical bypass (Bypass) or endovascular intervention (Endo) in 2 parallel trials. Cohort 1 included patients with single-segment great saphenous vein; cohort 2 included those lacking suitable single-segment great saphenous vein. HRQoL was assessed over the trial duration using Vascular Quality-of-Life (VascuQoL), European Quality-of-Life-5D (EQ-5D), the Short Form-12 (SF-12) Physical Component Summary (SF-12 PCS), SF-12 Mental Component Summary (SF-12 MCS), Utility Index Score (SF-6D R2), and numeric rating scales of pain. HRQoL was summarized by cohort and compared within and between groups using mixed-model linear regression., Results: A total of 1193 and 335 patients in cohorts 1 and 2 with a mean follow-up of 2.9 and 2.0 years, respectively, were analyzed. In cohort 1, HRQoL significantly improved from baseline to follow-up for both groups across all measures. For example, mean (SD) VascuQoL scores were 3.0 (1.3) and 3.0 (1.2) for Bypass and Endo at baseline and 4.7 (1.4) and 4.8 (1.5) over follow-up. There were significant group differences favoring Endo when assessed with VascuQoL (difference, -0.14 [95% CI, -0.25 to -0.02]; P =0.02), SF-12 MCS (difference, -1.03 [95% CI, -1.89 to -0.18]; P =0.02), SF-6D R2 (difference, -0.01 [95% CI, -0.02 to -0.001]; P =0.03), numeric rating scale pain at present (difference, 0.26 [95% CI, 0.03 to 0.49]; P =0.03), usual level during previous week (difference, 0.26 [95% CI, 0.04 to 0.48]; P =0.02), and worst level during previous week (difference, 0.29 [95% CI, 0.02 to 0.56]; P =0.04). There was no difference between treatment arms on the basis of EQ-5D (difference, -0.01 [95% CI, -0.03 to 0.004]; P =0.12) or SF-12 PCS (difference, -0.41 [95% CI, -1.2 to 0.37]; P =0.31). In cohort 2, HRQoL also significantly improved from baseline to the end of follow-up for both groups based on all measures, but there were no differences between Bypass and Endo on any measure., Conclusions: Among patients with chronic limb-threatening ischemia deemed eligible for either Bypass or Endo, revascularization resulted in significant and clinically meaningful improvements in HRQoL. In patients with an available single-segment great saphenous vein for bypass, but not among those without one, Endo was statistically superior on some HRQoL measures; however, these differences were below the threshold of clinically meaningful difference., Competing Interests: Disclosures M.T.M. is an advisor to Janssen. A.F. is an advisor to Sanifit. K.R. receives income as a consultant or member of a scientific advisory board for the following entities: Abbott Vascular, Althea Medical, Angiodynamics, Auxetics, Becton-Dickinson, Boston Scientific, Contego, Crossliner, Innova Vascular, InspireMD, Janssen/Johnson and Johnson, Magneto, Mayo Clinic, MedAlliance, Medtronic, Neptune Medical, Penumbra, Philips, Surmodics, Terumo, Thrombolex, Truvic, Vasorum, and Vumedi. K.R. owns equity or stock options in the following entities: Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Crossliner, Cruzar Systems, Endospan, Imperative Care/Truvic, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Prosomnus, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vasorum, and Vumedi. K.R. or his institution (on his behalf) receives research grants from the following entities: National Institutes of Health, Abiomed, Boston Scientific, Novo Nordisk Foundation, Penumbra, and Gettinge-Atrium. K.R. serves as a member of the board of directors of the National Pulmonary Embolism Response Team Consortium. M.S.C. is a Data Safety Monitoring Board member for an Abbott Vascular Clinical Trial. J.J.S. received an education grant from WL Gore paid to Boston University and an education grant from Becton Dickinson paid to Boston University. M.D.D. is a consultant for Cook Medical, WL Gore, and Boston Scientific. M.R.J. is a part-time employee for Boston Scientific. B.G. is a consultant to Surmodics and Hart Clinical Consultants. J.A.K. was a consultant and speaker for Cook Medical during the time of the study. The other authors report no conflicts.

Objectives: There has been significant variability in practice patterns and equipoise regarding treatment approach for chronic limb-threatening ischemia (CLTI). We aimed to assess treatment preferences of Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) investigators prior to and following the trial., Methods: An electronic 60-question survey was sent to 1180 BEST-CLI investigators in 2022, after trial conclusion and before announcement of results. Investigators' preferences were assessed across clinical scenarios for both open (OPEN) and endovascular (ENDO) revascularization strategies. Vascular surgeon (VS) surgical and ENDO preferences were compared with a 2010 survey administered to prospective investigators before trial funding., Results: For the 2022 survey, the response rate was 20.2% and was comprised of VSs (76.3%), interventional cardiologists (11.4%) and interventional radiologists (11.6%). The majority (72.6%) were in academic practice and 39.1% were in practice for >20 years. During initial CLTI work-up, 65.8%, 42.6%, and 55.9% of respondents always or usually ordered an arterial duplex, computed tomography angiography, and vein mapping, respectively. The most common practice distribution between ENDO and OPEN procedures was 70/30. Postoperatively, a majority reported performing routine duplex surveillance of vein bypass (99%), prosthetic bypass (81.9%), and ENDO interventions (86%). A minority reported always or usually using the wound, ischemia, and foot infection (WIfI) criteria (25.8%), GLASS (8.3%), and a risk calculator (14.8%). More than one-half (52.9%) agreed that the statement "no bridges are burned with an ENDO-first approach" was false. Intervention choice was influenced by availability of the operating room or ENDO suite, personal schedule, and personal skill set in 30.1%, 18.0%, and 45.9% of respondents, respectively. Most respondents reported routinely using paclitaxel-coated balloons (88.1%) and stents (67.5%); however, 73.3% altered practice when safety concerns were raised. Among surgeons, 17.8%, 2.9%, and 10.3% reported performing >10 annual alternative autogenous vein bypasses, composite vein composite vein bypasses, and bypasses to pedal targets, respectively. Among all interventionalists, 8%, 24%, and 8% reported performing >10 annual radial access procedures, pedal or tibial access procedures, and pedal loop revascularizations. The majority (89.1%) of respondents felt that CLTI teams improved care; however, only 23.2% had a defined team. The effectiveness of the teamwork at institutions was characterized as highly effective in 42.5%. When comparing responses by VSs to the 2010 survey, there were no changes in preferred treatment based on Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) II classification or conduit preference. In 2022, OPEN surgery was preferred more for a popliteal occlusion. For clinical scenarios, there were no differences except a decreased proportion of respondents who felt there was equipoise for major tissue loss for major tissue loss (43.8% vs 31.2%) and increased ENDO choice for minor tissue loss (17.6% vs 30.8%) (P < .05)., Conclusions: There is a wide range of practice patterns among vascular specialists treating CLTI. The majority of investigators in BEST-CLI had experience in both advanced OPEN and ENDO techniques and represent a real-world sample of technical expertise. Over the course of the decade of the BEST-CLI trial, there was overall similar equipoise among VSs., Competing Interests: Disclosures A.F. has received a grant from the Novo Nordisk Foundation; is a consultant for Sanifit, LeMaitre, and BioGenCell; and is on the advisory board of Dialysis-X and iThera Medical. M.M. is an advisor for Janssen. K.G. is an advisory board member for Boston Scientific. K.R. receives income as a consultant or member of a scientific advisory board for the following entities: Abbott Vascular; Althea Medical; Angiodynamics; Auxetics; Becton-Dickinson; Boston Scientific; Contego; Crossliner; Innova Vascular; Inspire MD; Janssen/Johnson and Johnson; Magneto; Mayo Clinic; MedAlliance; Medtronic; Neptune Medical; Penumbra; Philips; Surmodics; Terumo; Thrombolex; Truvic; Vasorum; Vumedi. KR owns equity or stock options in the following entities: Access Vascular; Aerami; Althea Medical; Auxetics; Contego; Crossliner; Cruzar Systems; Endospan; Imperative Care/Truvic; Innova Vascular; InspireMD; JanaCare; Magneto; MedAlliance; Neptune Medical; Orchestra; Prosomnus; Shockwave; Skydance; Summa Therapeutics; Thrombolex; Vasorum; Vumedi. K.R. or his institution (on my behalf) receive research grants from the following entities: NIH; Abiomed; Boston Scientific; Novo Nordisk Foundation; Penumbra; Gettinge-Atrium. K.R. serves as a member of the Board of Directors of the following organization: The National PERT ConsortiumTM., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Anticipated perioperative morbidity is an important factor for choosing a revascularization method for chronic limb-threatening ischemia (CLTI). Our goal was to assess systemic perioperative complications of patients treated with surgical and endovascular revascularization in the Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial., Methods: BEST-CLI was a prospective randomized trial comparing open (OPEN) and endovascular (ENDO) revascularization strategies for patients with CLTI. Two parallel cohorts were studied: Cohort 1 included patients with adequate single-segment great saphenous vein (SSGSV), whereas Cohort 2 included those without SSGSV. Data were queried for major adverse cardiovascular events (MACE-composite myocardial infarction, stroke, death), non-serious (non-SAEs) and serious adverse events (SAEs) (criteria-death/life-threatening/requiring hospitalization or prolongation of hospitalization/significant disability/incapacitation/affecting subject safety in trial) 30 days after the procedure. Per protocol analysis was used (intervention received without crossover), and risk-adjusted analysis was performed., Results: There were 1367 patients (662 OPEN, 705 ENDO) in Cohort 1 and 379 patients (188 OPEN, 191 ENDO) in Cohort 2. Thirty-day mortality in Cohort 1 was 1.5% (OPEN 1.8%; ENDO 1.3%) and in Cohort 2 was 1.3% (2.7% OPEN; 0% ENDO). MACE in Cohort 1 was 4.7% for OPEN vs 3.13% for ENDO (P = .14), and in Cohort 2, was 4.28% for OPEN and 1.05% for ENDO (P = .15). On risk-adjusted analysis, there was no difference in 30-day MACE for OPEN vs ENDO for Cohort 1 (hazard ratio [HR] 1.5; 95% confidence interval [CI], 0.85-2.64; P = .16) or Cohort 2 (HR, 2.17; 95% CI, 0.48-9.88; P = .31). The incidence of acute renal failure was similar across interventions; in Cohort 1 it was 3.6% for OPEN vs 2.1% for ENDO (HR, 1.6; 95% CI, 0.85-3.12; P = .14), and in Cohort 2, it was 4.2% OPEN vs 1.6% ENDO (HR, 2.86; 95% CI, 0.75-10.8; P = .12). The occurrence of venous thromboembolism was low overall and was similar between groups in Cohort 1 (OPEN 0.9%; ENDO 0.4%) and Cohort 2 (OPEN 0.5%; ENDO 0%). Rates of any non-SAEs in Cohort 1 were 23.4% in OPEN and 17.9% in ENDO (P = .013); in Cohort 2, they were 21.8% for OPEN and 19.9% for ENDO (P = .7). Rates for any SAEs in Cohort 1 were 35.3% for OPEN and 31.6% for ENDO (P = .15); in Cohort 2, they were 25.5% for OPEN and 23.6% for ENDO (P = .72). The most common types of non-SAEs and SAEs were infection, procedural complications, and cardiovascular events., Conclusions: In BEST-CLI, patients with CLTI who were deemed suitable candidates for open lower extremity bypass surgery had similar peri-procedural complications following either OPEN or ENDO revascularization: In such patients, concern about risk of peri-procedure complications should not be a deterrent in deciding revascularization strategy. Rather, other factors, including effectiveness in restoring perfusion and patient preference, are more relevant., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The use of optimal medical therapy (OMT) in patients with chronic limb-threatening ischemia (CLTI) has not been well-studied. The Best Endovascular vs Best Surgical Therapy in Patients with CLTI study (BEST-CLI) is a multicenter, randomized, controlled trial sponsored by the National Institutes of Health comparing revascularization strategies in patients with CLTI. We evaluated the use of guideline-based OMT among patients with CLTI at the time of their enrollment into the trial., Methods: A multidisciplinary committee defined OMT criteria related to blood pressure and diabetic management, lipid-lowering and antiplatelet medication use, and smoking status for patients enrolled in BEST-CLI. Status reports indicating adherence to OMT were provided to participating sites at regular intervals. Baseline demographic characteristics, comorbid medical conditions, and use of OMT at trial entry were evaluated for all randomized patients. A linear regression model was used to identify the relationship of predictors to the use of OMT., Results: At the time of randomization (n = 1830 total enrolled), 87% of patients in BEST-CLI had hypertension, 69% had diabetes, 73% had hyperlipidemia, and 35% were currently smoking. Adherence to four OMT components (controlled blood pressure, not currently smoking, use of one lipid-lowering medication, and use of an antiplatelet agent) was modest. Only 25% of patients met all four OMT criteria; 38% met three, 24% met two, 11% met only one, and 2% met none. Age ≥80 years, coronary artery disease, diabetes, and Hispanic ethnicity were positively associated, whereas Black race was negatively associated, with the use of OMT., Conclusions: A significant proportion of patients in BEST-CLI did not meet OMT guideline-based recommendations at time of entry. These data suggest a persistent major gap in the medical management of patients with advanced peripheral atherosclerosis and CLTI. Changes in OMT adherence over the course of the trial and their impact on clinical outcomes and quality of life will be assessed in future analyses., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The WIfI (Wound, Ischemia, foot Infection) stage measures the extent of wounds, ischemia, and foot infection in patients with chronic limb threatening ischemia (CLTI) and has been associated with the risk of major amputation. Patients with CLTI have impaired health-related quality of life (HRQoL), which can be multifactorial. We hypothesized that the severity of the limb threat (WIfI stage) would be associated with poor HRQoL among patients with CLTI presenting for revascularization., Methods: The dataset of the BEST-CLI (best endovascular versus best surgical therapy in patients with CLTI) trial, a prospective, randomized trial comparing open and endovascular revascularization strategies, was queried for HRQoL assessments at patient enrollment. The HRQoL assessments included (1) Vascular Quality of Life; (2) 12-item short form survey (SF-12), containing the utility index score (short-form six-dimension R2 utility index, incorporating physical, emotional, and mental well-being) and mental and physical components; and (3) the EQ-5D. Multivariable regression analysis was used to identify the independent associations with the baseline HRQoL assessments., Results: A total of 1568 patients with complete WIfI data were analyzed, of whom 71.5% were men. The WIfI distribution was 35.5% with stage 4, 29.6% with stage 3, 28.6% with stage 2, and 6.3% with stage 1. Patients presenting with WIfI stage 4, compared with stage 1 to 3, were more often men (74.9% vs 69.6%) and current smokers (25.4% vs. 17.6%), had had end-stage renal disease (13.3% vs 8.5%) and diabetes (83.6% vs 60.2%), were not independently ambulatory (56.8% vs 38.5%), and had had higher median morbidity scores (4 vs 3; P < .05 for all). On multivariable analysis, WIfI stage 4, compared with stage 1 to 3, was associated with lower SF-12 mental component scale scores (estimate, -2.43; 95% confidence interval, -3.73 to -1.13; P < .001) and short-form six-dimension R2 utility index scores (estimate, -0.02; 95% confidence interval, -0.03 to 0.001; P = .04). The WIfI stage was not independently associated with the baseline Vascular Quality of Life, SF-12 physical component scale, or EQ-5D assessments., Conclusions: WIfI stage was independently associated with poorer quality of life because of mental, rather than physical, health for patients with CLTI. Clinicians should be aware of the burden of mental stress borne by those with the greatest limb impairment., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes., Methods: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause., Results: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts., Conclusions: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI., Methods: We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007-2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson's correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients., Results: Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n = 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R= -0.61, P = 0.39)., Conclusions: Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management., Competing Interests: Conflicts of Interest: A.F.: Consultant for Sanifit. Matthew Menard: Scientific Advisory Board for Janssen; K.R.: multiple conflicts to be delivered under separate cover; No conflicts: J.S., M.E., P.G., M.S., M.V., M.V., T.H. report no conflicts., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To establish an enterprise initiative for improving health and health care through interoperable electronic health record (EHR) innovations., Materials and Methods: We developed a unifying mission and vision, established multidisciplinary governance, and formulated a strategic plan. Key elements of our strategy include establishing a world-class team; creating shared infrastructure to support individual innovations; developing and implementing innovations with high anticipated impact and a clear path to adoption; incorporating best practices such as the use of Fast Healthcare Interoperability Resources (FHIR) and related interoperability standards; and maximizing synergies across research and operations and with partner organizations., Results: University of Utah Health launched the ReImagine EHR initiative in 2016. Supportive infrastructure developed by the initiative include various FHIR-related tooling and a systematic evaluation framework. More than 10 EHR-integrated digital innovations have been implemented to support preventive care, shared decision-making, chronic disease management, and acute clinical care. Initial evaluations of these innovations have demonstrated positive impact on user satisfaction, provider efficiency, and compliance with evidence-based guidelines. Return on investment has included improvements in care; over $35 million in external grant funding; commercial opportunities; and increased ability to adapt to a changing healthcare landscape., Discussion: Key lessons learned include the value of investing in digital innovation initiatives leveraging FHIR; the importance of supportive infrastructure for accelerating innovation; and the critical role of user-centered design, implementation science, and evaluation., Conclusion: EHR-integrated digital innovation initiatives can be key assets for enhancing the EHR user experience, improving patient care, and reducing provider burnout., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Although randomized controlled trials (RCTs) provide the most reliable form of scientific evidence, they are challenging to complete because of a variety of enrollment obstacles. We evaluated obstacles in a large RCT by comparing survey results at high-performing sites (HPS) and low-performing sites (LPS)., Methods: The Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial is a prospective, pragmatic, multicenter, and multispecialty RCT that will compare clinical outcomes, quality of life, and cost in patients with CLI randomized to surgical bypass or endovascular therapy. BEST-CLI aims to enroll 2100 patients at 160 sites in North America, Europe, and New Zealand. We surveyed the 30 HPS and 30 LPS to assess perceptions of enrollment obstacles. HPS were defined by enrollment of 0.5 subjects or more per month or more than 8 total subjects enrolled. LPS were defined by enrollment of 0.1 subjects per month or only 1 subject total. Responses were compared by site performance status., Results: There were 22 of 30 (73%) HPS and 14 of 30 (47%) LPS that answered the survey (P = 0.06), including 17 investigators and 31 coordinators. The mean total enrollment and rate of enrollment at HPS and LPS were 12.5 subjects at 1.5 subjects/month and 1.0 subject at 0.1 subjects/month, respectively. The most common barrier to enrollment at HPS was difficulty convincing patients and their families to participate (36%), whereas at LPS both difficulty convincing patients and difficulty motivating investigators to enroll (29% each) were most frequently cited. At HPS, the most common obstacle to consenting patients for the trial was patient/family having strong preference toward revascularization strategy (32%) and at LPS it was patient/family not wanting to have treatment chosen at random (36%). At 55% of HPS and 43% of LPS, the trial team was reported as extremely collaborative (P = 0.73), whereas 68% of HPS and 64% of LPS reported having identified a trial champion on their team (P = 1). The most restrictive perceived enrollment criterion at HPS was prior index limb stenting with significant restenosis (32%), whereas at LPS it was excessive risk for surgical bypass (43%). Materials to aid enrollment were used equally at HPS and LPS: patient brochures at 59% HPS and 64% LPS (P = 1); investigator talking points at 45% of HPS and 36% of LPS (P = 0.73)., Conclusions: Patient perceptions and investigator biases are significant challenges to enrollment in large RCTs. In the BEST-CLI trial, difficulty convincing patients and families to allow treatment randomization and difficulty in motivating investigators were major enrollment obstacles., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There is limited guidance available in the literature for establishing clinical decision support (CDS) governance and improving CDS effectiveness in a pragmatic, resource-efficient manner. Here, we describe how University of Utah Health established enterprise CDS governance in 2015 leveraging existing resources. Key components of the governance include a multi-stakeholder CDS Committee that vets new requests and reviews existing content; a requirement that proposed CDS is actually desired by intended recipients; coordination with other governance bodies; basic data analytics to identify high-frequency, low-value CDS and monitor progress; active solicitation of user issues; the transition of alert and reminder content to other, more appropriate areas in the electronic health record; and the judicious use of experimental designs to guide decision-making regarding CDS effectiveness. In the three years since establishing this governance, new CDS has been continuously added while the overall burden of clinician-facing alerts and reminders has been reduced by 53.8%.

Objective: To develop expeditiously a pragmatic, modular, and extensible software framework for understanding and improving healthcare value (costs relative to outcomes)., Materials and Methods: In 2012, a multidisciplinary team was assembled by the leadership of the University of Utah Health Sciences Center and charged with rapidly developing a pragmatic and actionable analytics framework for understanding and enhancing healthcare value. Based on an analysis of relevant prior work, a value analytics framework known as Value Driven Outcomes (VDO) was developed using an agile methodology. Evaluation consisted of measurement against project objectives, including implementation timeliness, system performance, completeness, accuracy, extensibility, adoption, satisfaction, and the ability to support value improvement., Results: A modular, extensible framework was developed to allocate clinical care costs to individual patient encounters. For example, labor costs in a hospital unit are allocated to patients based on the hours they spent in the unit; actual medication acquisition costs are allocated to patients based on utilization; and radiology costs are allocated based on the minutes required for study performance. Relevant process and outcome measures are also available. A visualization layer facilitates the identification of value improvement opportunities, such as high-volume, high-cost case types with high variability in costs across providers. Initial implementation was completed within 6 months, and all project objectives were fulfilled. The framework has been improved iteratively and is now a foundational tool for delivering high-value care., Conclusions: The framework described can be expeditiously implemented to provide a pragmatic, modular, and extensible approach to understanding and improving healthcare value., (© The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Context: Extreme obesity is associated with health and cardiovascular disease risks. Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term, long-term outcomes are uncertain., Objective: To examine the association of Roux-en-Y gastric bypass (RYGB) surgery with weight loss, diabetes mellitus, and other health risks 6 years after surgery., Design, Setting, and Participants: A prospective Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese (body mass index [BMI] ≥ 35) participants aged 18 to 72 years (82% women; mean BMI, 45.9; 95% CI, 31.2-60.6) who sought and received RYGB surgery (n = 418), sought but did not have surgery (n = 417; control group 1), or who were randomly selected from a population-based sample not seeking weight loss surgery (n = 321; control group 2)., Main Outcome Measures: Weight loss, diabetes, hypertension, dyslipidemia, and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment., Results: Six years after surgery, patients who received RYGB surgery (with 92.6% follow-up) lost 27.7% (95% CI, 26.6%-28.9%) of their initial body weight compared with 0.2% (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, -1.2% to 1.2%) in control group 2. Weight loss maintenance was superior in patients who received RYGB surgery, with 94% (95% CI, 92%-96%) and 76% (95% CI, 72%-81%) of patients receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after surgery, respectively. Diabetes remission rates 6 years after surgery were 62% (95% CI, 49%-75%) in the RYGB surgery group, 8% (95% CI, 0%-16%) in control group 1, and 6% (95% CI, 0%-13%) in control group 2, with remission odds ratios (ORs) of 16.5 (95% CI, 4.7-57.6; P < .001) vs control group 1 and 21.5 (95% CI, 5.4-85.6; P < .001) vs control group 2. The incidence of diabetes throughout the course of the study was reduced after RYGB surgery (2%; 95% CI, 0%-4%; vs 17%; 95% CI, 10%-24%; OR, 0.11; 95% CI, 0.04-0.34 compared with control group 1 and 15%; 95% CI, 9%-21%; OR, 0.21; 95% CI, 0.06-0.67 compared with control group 2; both P < .001). The numbers of participants with bariatric surgery-related hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for the RYGB surgery group and 2 control groups, respectively., Conclusion: Among severely obese patients, compared with nonsurgical control patients, the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years.

Objectives: The objective of this study was to test the hypothesis that gastric bypass surgery (GBS) would favorably impact cardiac remodeling and function., Background: GBS is increasingly used to treat severe obesity, but there are limited outcome data., Methods: We prospectively studied 423 severely obese patients undergoing GBS and a reference group of severely obese subjects that did not have surgery (n = 733)., Results: At a 2-year follow up, GBS subjects had a large reduction in body mass index compared with the reference group (-15.4 ± 7.2 kg/m(2) vs. -0.03 ± 4.0 kg/m(2); p < 0.0001), as well as significant reductions in waist circumference, systolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, and insulin resistance. High-density lipoprotein cholesterol increased. The GBS group had reductions in left ventricular (LV) mass index and right ventricular (RV) cavity area. Left atrial volume did not change in GBS but increased in reference subjects. In conjunction with reduced chamber sizes, GBS subjects also had increased LV midwall fractional shortening and RV fractional area change. In multivariable analysis, age, change in body mass index, severity of nocturnal hypoxemia, E/E', and sex were independently associated with LV mass index, whereas surgical status, change in waist circumference, and change in insulin resistance were not., Conclusions: Marked weight loss in patients undergoing GBS was associated with reverse cardiac remodeling and improved LV and RV function. These data support the use of bariatric surgery to prevent cardiovascular complications in severe obesity., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Warfarin remains a difficult drug to manage due to a narrow therapeutic range and wide interindividual variability in dose requirements. The relationship between warfarin sensitivity and CYP2C9 and VKORC1 variants is strong, and is the basis for several proposed dosing algorithms. Here a gene-based dosing algorithm was compared with standard of care dosing in patients receiving warfarin to prevent venous thromboembolism after joint replacement surgery. Participants (n = 229) were adults (> or =18 years) undergoing elective total hip or knee arthroplasty and receiving warfarin under the direction of a dedicated anticoagulation services team. Patients were assigned to genotype-based or standard of care dosing arms in an alternating fashion. Initial dose for patients was determined by validated algorithms from Sconce 2005 and Pendleton 2008. Management was based on INR, but dose was adjusted less aggressively for patients with CYP2C9 variants. The primary endpoint was reduction in the incidence of adverse events; additional endpoints included time to first therapeutic INR (1.8-2.9), time to first supratherapeutic INR, and percent of INR determinations that fell below, within, and above the therapeutic range. Endpoints did not achieve statistical significance, possibly due to the management of this study by a dedicated and experienced anticoagulation services team. Trends in the data suggest that patients with genetic variants progressed to a therapeutic INR faster than patients in whom genetic variants were not detected, and there were fewer adverse events in the genotype-based dosing arm. In addition, the results of this study confirm those of others demonstrating clear relationship of genotype for CYP2C9 and VKORC1 with warfarin dose requirements; as the number of variants in these genes increases, the dose requirement decreases. Of note, the gene-based algorithm utilized here significantly underpredicted the dose requirement for participants with no variants, indicating that patients with no variants should be managed with a different algorithm than patients who inherit genetic variants in CYP2C9 and/or VKORC1. In conclusion, gene-based dosing did not improve warfarin management as defined by INR dose response, using the described protocols for implementation. Findings suggest alternative strategies for dosing based on the presence or absence of genetic variants is needed.

Venous thromboembolism (VTE) is a complication after joint arthroplasty, and pharmacologic prophylaxis is recommended to reduce this risk. Warfarin is often used, but initial dosing and management can be difficult. We studied a single-center prospective cohort of consecutive (n = 351) post-joint arthroplasty/revision patients who were initiated on warfarin using a new initiation nomogram and then discharged to home with home health services. The mean time to an international normalized ratio (INR) of 2.0 or higher was 5 days, with a mean INR of 2.1 on the fifth postoperative day. Two patients (0.6%) had an INR higher than 5 in the first 10 days of therapy. Adverse events were uncommon: 4 patients (1.14%) had VTE, 1 had major bleeding episode, and 6 patients (1.7%) had minor bleeding. A specific warfarin dosing nomogram managed by an anticoagulation service and used in joint arthroplasty/revision patients who are discharged to home with home health services leads to effective anticoagulation with few associated adverse events., (2010 Elsevier Inc. All rights reserved.)

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight-loss intervention. Three groups of severely obese subjects (N = 1,156, BMI >or= 35 kg/m(2)) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population-based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes-related variables, resting metabolic rate (RMR), sleep apnea, and health-related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF-36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux-en-Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight-loss intervention was highly effective for weight loss, improved health-related quality of life, and resolution of major obesity-associated complications measured at 2 years.

The efficacy of cyromazine, continuously released from intraruminal capsules at dose rates from 0.5 to 2 mg kg-1 d-1, was evaluated against implants of eggs and first instar larvae of Lucilia cuprina on Merino sheep. Estimates from the non-linear relationship between the success of implants and plasma concentrations showed that 95 per cent protection of sheep could be achieved at a mean release rate of 1.39 mg kg-1 d-1 cyromazine which gave rise to a mean plasma concentration of 0.26 mg litre-1. Present formulations allowed protection for about 90 days in a 40 kg sheep. The 'square wave' type of release profile provided negligible suboptimal dosing thus limiting the potential for selection of resistance. Systemic application of cyromazine provides control of covert and overt strike among sheep and could be used in ecologically based strategies for the control of L. cuprina populations.

The efficiency of 2-cyclopropylamino-4, 6-diamino-s-triazine CGA-72662 (proposed common name: cyromazine) for the control of blowfly strike was tested in fly cage and field trials on sheep. The safety to sheep and physico-chemical properties of the compound as they relate to blowfly control were also assessed. When the sheep were thoroughly jetted with a solution of CGA-72662 containing 1g of active ingredient per litre, the mean incidence of fly strike in 7 field trials was reduced from 16.5% to 1.5% over a period of 9 weeks. The incidence of strike in the treated sheep in 2 insectary tests, which imposed levels of fly activity far in excess of that usually encountered in the field, was reduced from 93% and 73% in untreated sheep to 2% and nil respectively over a period of 8 weeks. Jetting with CGA-72662 solutions 100 times greater than the recommended concentration did not produce any side effects in sheep. Three treatments at twice the recommended concentration during the first trimester did not affect pregnant ewes nor their progeny. The compound was safe to use in combination with common anthelmintics and with sheep dips used for control of lice. CGA-72662 was stable in solution. No stripping occurred in dips and it persisted on wool for a considerable period. A satisfactory alternative to the organophosphorus insecticides has been found in CGA-72662, since it provided a substantial increase in residual protection against blowfly strike with a high degree of safety.

In a field experiment, moderate to heavy natural concomitant infections with immature and mature Fasciola hepatica were treated with triclahendazole at a dose rate of 10 mg/kg and an efficiency of 99.8% was achieved. Subsequent treatments of all susceptible farm animals at the same dose rate at intervals of eight to eleven weeks were carried out for 14 months; no patent infections could be detected in sheep and cattle during the whole period. Evidence is presented that pasture contamination with liver fluke was reduced to a negligible level for a further 12 months after the final treatment. It is suggested that, if regular treatments with triclabendazole are given within the pre-patent period of Fasciola hepatica infection for the whole season, the infection can be eradicated or reduced to such a low level that control of the disease could be maintained with less frequent strategic drenching for a considerable period.

A new benzimidazole anthelmintic, triclabendazole (CGA-89317) was found to be highly efficient against mature and early immature Fasciola hepatica infections in sheep. At the dose rate of 2.5 mg/kg the efficiency was 90 and 98 per cent against flukes aged eight and 12 weeks respectively. At 5 mg/kg the drug was 92 and 98 per cent efficient against flukes aged four and eight weeks respectively and 100 per cent against 12-week-old flukes. An efficiency of 93 and 98 per cent was achieved against one-week-old flukes and 99 to 100 per cent against flukes aged two to four weeks at 10 mg/kg. At this dose rate the drug had 100 per cent efficiency against six-week-old flukes. If the dose was increased to 15 mg/kg, 98 per cent efficiency was achieved one day after infection. Triclabendazole was equally efficient when administered orally or by intraruminal or intra-abomasal injection. The maximum tolerated dose of 200 mg/kg was established.

Methidathion applied to cattle as a pour-on insecticide for control of lice (predominantly Linognathus vituli, but also Haematopinus eurysternus and Damalinia bovis) caused a reduction in the lice population of approximately 98% to 99% in laboratory trials at the minimum recommended dose of 4 mg/kg and a 98.8% to 100% efficiency was achieved in field trials. In a comparative efficiency trial in the laboratory methidathion at 3.5 to 5 mg/kg reduced the lice population by 98.8% to 99%, fenthion by 98.5% at 4.5 mg/kg and famphur by 99.7% at 16.5 mg/kg. Methidathion was tolerated by calves aged 15 to 20 weeks at dose rates up to 40 mg/kg indicating an approximate 7 fold safety margin, but 1 of 4 calves treated at 50 mg/kg died following treatment. Treatment with fenthion at 50 mg/kg, 7.4 times the average recommended rate, famphur at 75 mg/kg, 3 times the average rate and chlorpyrifos at 85 mg/kg, 5 times average rate, caused reductions in whole blood cholinesterase activity of 52%, 27% and 47% respectively which were similar to the reductions in cholinesterase activity found in calves treated with methidathion at similar levels above the recommended commercial dose rates. It was found that 2 day old calves were more sensitive to treatment with methidathion than calves 9 or 16 days old. A further 11,900 cattle of varying age, breed and sex were treated with methidathion under field conditions at the recommended rate of 4 to 8 mg/kg, and 534 cattle were treated at 24 mg/kg without any signs of toxicity.