Characterization of cardiovascular serious adverse events after bypass or endovascular revascularization for limb-threatening ischemia in the BEST-CLI trial.

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.

Quality of Life in Patients With Chronic Limb-Threatening Ischemia Treated With Revascularization.

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.

Investigator attitudes on equipoise and practice patterns in the BEST-CLI trial.

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.

Perioperative complications following open or endovascular revascularization for chronic limb-threatening ischemia in the BEST-CLI Trial.

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.

Baseline modern medical management in the BEST-CLI trial.

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.

Relationship between WIfI stage and quality of life at revascularization in the BEST-CLI trial.

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.

Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

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.).

Participation in a Chronic Limb Threatening Ischemia Randomized Trial Is Inversely Correlated With Regional Amputation Rate in Limb Threatening Ischemia Patients.

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.

Establishing a multidisciplinary initiative for interoperable electronic health record innovations at an academic medical center.

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.

Enrollment Obstacles in a Randomized Controlled Trial: A Performance Survey of Enrollment in BEST-CLI Sites.

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.

Value Driven Outcomes (VDO): a pragmatic, modular, and extensible software framework for understanding and improving health care costs and outcomes.

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.

Health benefits of gastric bypass surgery after 6 years.

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.

Favorable changes in cardiac geometry and function following gastric bypass surgery: 2-year follow-up in the Utah obesity study.

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.

Gene-based warfarin dosing compared with standard of care practices in an orthopedic surgery population: a prospective, parallel cohort study.

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.

Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese.

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.

A safe, effective, and easy to use warfarin initiation dosing nomogram for post-joint arthroplasty patients.

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.