Postoperative opioid prescribing patterns and use after vascular surgery.

The aim of this study was to assess postoperative opioid prescribing patterns, usage, and pain control after common vascular surgery procedures in order to develop patient centered best-practice guidelines. We performed a prospective review of opioid prescribing after seven common vascular surgeries at a rural, academic medical center from December 2016 to July 2017. A standardized telephone questionnaire was prospectively administered to patients ( n = 110) about opioid use and pain management perceptions. For comparison we retrospectively assessed opioid prescribing patterns ( n = 939) from July 2014 to June 2016 normalized into morphine milligram equivalents (MME). Prescribers were surveyed regarding opioid prescription attitudes, perceptions, and practices. Opioids were prescribed for 78% of procedures, and 70% of patients reported using opioid analgesia. In the prospective group, the median MMEs prescribed were: VEIN (31, n = 16), CEA (40, n = 14), DIAL (60, n = 17), EVAR (108, n = 8), INFRA (160, n = 16), FEM TEA (200, n = 11), and OA (273, n = 4). The median proportion of opioids used by patients across all procedures was only 30% of the amount prescribed across all procedures (range 14-64%). Patients rated the opioid prescribed as appropriate (59%), insufficient (16%), and overprescribed (25%), and pain as very well controlled (47%), well controlled (47%), poorly controlled (4%), and very poorly controlled (2%). In conclusion, we observed significant variability in opioid prescribing after vascular procedures. The overall opioid use was substantially lower than the amount prescribed. These data enabled us to develop guidelines for opioid prescribing practice for our patients.

Surveillance and Management of Troponin Elevation after Vascular Surgery.

BACKGROUND: Postopertive troponin elevation may occur without typical or atypical cardiac symptoms and is associated with an increased 30-day morbidity and mortality. The objective of the study was to implement a quality improvement initiative of postoperative troponin surveillance algorithm aimed at intensifying medical management after vascular surgery. METHODS: We conducted a single-center study of postoperative troponin surveillance after vascular surgery (n = 201) at a tertiary care, academic medical center from January to December 2016. Troponin surveillance was performed on postoperative days 1-3 after carotid endarterectomy, endovascular aortic repair, infrainguinal bypass, open abdominal aortic aneurysm repair, peripheral vascular intervention, and suprainguinal bypass, regardless of cardiac symptoms. Patients with troponin I elevation (>0.034 ng/mL) were managed with a treatment algorithm which included single or dual antiplatelet (AP) agent, high-intensity statin therapy, smoking cessation consultation, and outpatient cardiology consultation and stress testing. Patients with troponin elevation ≥1.0 ng/mL received inpatient cardiology consultation. We assessed adherence to the protocol for intensification of best medical therapy defined as high-dose statin therapy, increase in AP therapy, and smoking cessation consultation according to the established algorithm. RESULTS: Troponin elevation was recorded in 17% (34/201) of patients and was associated with cardiac symptoms in 8 patients (24%), while 26 (76%) patients had an asymptomatic abnormal troponin on postoperative surveillance. One patient was excluded due to death immediately after SUPRA, resulting in 200 patients. Troponin elevation ≥1.0 ng/mL occurred in 11 asymptomatic patients (5.5%). Any intensification of medical therapy was instituted in 76% of patients with elevated troponin and included high-intensity statin therapy (58%), increase in AP therapy (18%), and smoking cessation consultation (66%). Once an elevated troponin level was recognized, 52% of our patients received cardiology consultation with an increased likelihood (100%) in patients with troponin ≥1 ng/mL (P < 0.001). Adherence to outpatient stress testing was 66%. Intensification of medical therapy was not significantly different between patients with abnormal troponin values, >0.034-1.0 (n = 23) versus ≥1.0 ng/mL (n = 10); statin therapy (P = 1.0), AP (P = 0.34), and smoking cessation (P = 1.0). One-year mortality was higher in patients with postoperative troponin elevation than those with normal postoperative troponin levels (12% vs. 2.4%; P = 0.03). CONCLUSIONS: Routine postoperative troponin surveillance results in intensification of statin therapy in patients with asymptomatic troponin elevation. Further study is needed to determine if this approach reduces long-term cardiovascular morbidity and mortality.

Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747).

OBJECTIVE: To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC). PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 × 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. RESULTS: The per-patient cost for ZA was £12 667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was £8 005. Sr89 was associated with a cost of £13 230, £1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively. CONCLUSIONS: The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness-to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources.

Proctors exploit three-dimensional ghost tools during clinical-like training scenarios: a preliminary study.

PURPOSE: In this study, we examine three-dimensional (3D) proctoring tools (i.e., semitransparent ghost tools overlaid on the surgeon's field of view) on realistic surgical tasks. Additionally, we develop novel, quantitative measures of whether proctors exploit the additional capabilities offered by ghost tools. METHODS: Seven proctor-trainee pairs completed realistic surgical tasks such as tissue dissection and suturing in a live porcine model using 3D ghost tools on the da Vinci Xi Surgical System. The usability and effectiveness of 3D ghost tools were evaluated using objective measures of proctor performance based on proctor hand movements and button presses, as well as post-study questionnaires. RESULTS: Proctors exploited the capabilities of ghost tools, such as 3D hand movement (p < 0.001), wristedness (p < 0.001), finger pinch gestures (p < 0.001), and bimanual hand motions (p < 0.001). The median ghost tool excursion distances across proctors in the x-, y-, and z-directions were 57.6, 31.9, and 50.7, respectively. Proctors and trainees consistently evaluated the ghost tools as effective across multiple categories of mentoring. Trainees found ghost tools more helpful than proctors across all categories (p < 0.05). CONCLUSIONS: Proctors exploit the augmented capabilities of 3D ghost tools during clinical-like training scenarios. Additionally, both proctors and trainees evaluated ghost tools as effective mentoring tools, thereby confirming previous studies on simple, inanimate tasks. Based on this preliminary work, advanced mentoring technologies, such as 3D ghost tools, stand to improve current telementoring and training technologies in robot-assisted minimally invasive surgery.

Prospective Study of Postoperative Glycemic Control with a Standardized Insulin Infusion Protocol after Infrainguinal Bypass and Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: The aim of this study is to examine the effect of moderate postoperative glycemic control in diabetic and nondiabetic patients undergoing infrainguinal bypass (INFRA) or open abdominal aortic aneurysm (OAAA) repair. METHODS: In a single center prospective study, we investigated postoperative glycemic control using a standardized insulin infusion protocol after elective INFRA bypass (n = 53, 62%) and OAAA repair (n = 33, 38%) between January 2013 and March 2015. The primary end point was optimal glycemic control, defined as having ≥85% of blood glucose values within the 80-150 mg/dL target range. Suboptimal glycemic control was defined as <85% of blood glucose values within the blood glucose target range. Secondary end points included in-hospital and 30-day surgical site infection (SSI) rates, composite adverse events, length of stay (LOS), and hospital cost. RESULTS: Optimal glycemic control was achieved more commonly after OAAA repair than INFRA bypass (85% vs. 64%, P = 0.04). Moderate hypoglycemia (<70 mg/dL) was observed in 32 (37%) patients, while severe hypoglycemia (<50 mg/dL) was observed in 6 (7%) patients. SSI at 30 days was more common after INFRA bypass (n = 15, 29%) than OAAA repair (n = 2, 6%) (P = 0.01). In-hospital (6% vs. 6%, P = 1.0) and 30-day (24% vs. 22%, P = 1.0) SSI rates were similar for optimal versus suboptimal glycemic control patients after INFRA bypass. In-hospital (4% vs. 0%, P = 1.0) and 30-day (4% vs. 0%, P = 1.0) SSI rates were similar for optimal versus suboptimal glycemic control patients after OAAA repair. The percentage of blood glucose > 250 mg/dL was similar for patients with and without SSI (3% vs. 2%, P = 0.36). Adverse cardiac and pulmonary events after INFRA bypass were similar between groups (9% vs. 21%, P = 0.23; 0% vs. 5%, P = 0.36, respectively). Adverse cardiac and pulmonary events after OAAA repair were similar between groups (2% vs. 0%, P = 1.0; 4% vs. 0%, P = 1.0, respectively). Mean LOS was significantly lower in patients with optimal glycemic control after INFRA bypass (4.2 vs. 7.3 days, P = 0.02). Mean LOS was similar after OAAA repair for patients with optimal and suboptimal control (5.8 vs. 6.4 days, P = 0.46). Inpatient hospital costs after INFRA bypass were lower for the group with optimal (median $25,012, interquartile range [IQ] range $21,726-28,331) versus suboptimal glycemic control (median $28,944, IQ range 24,773-41,270, P = 0.02). CONCLUSIONS: Postoperative hyperglycemia is common after INFRA bypass and OAAA repair and can be effectively ameliorated with an insulin infusion protocol. The protocol was low risk with reduced LOS and cost after INFRA bypass. Complications including SSI were not reduced in patients with optimal perioperative glycemic control.

Factors that determine the length of stay after carotid endarterectomy represent opportunities to avoid financial losses.

BACKGROUND: A postoperative length of stay (LOS) >1 day after elective surgery incurs financial losses for hospitals, given fixed diagnosis-related group-based reimbursement. We sought to identify factors leading to a prolonged LOS (>1 postoperative day) after carotid endarterectomy (CEA). METHODS: Patients undergoing CEA in 23 centers of the Vascular Study Group of New England between 2003 and 2011 (n = 8860) were analyzed. Only elective, primary CEAs were analyzed, leaving a study cohort of 7108 procedures. Hierarchical multivariable logistic regression analysis was performed to identify predictors of a postoperative LOS >1 day. A Knaus-Wagner chi-pie analysis was performed to determine the relative contributions of each significant covariate to a postoperative LOS >1 day. RESULTS: A postoperative LOS >1 day occurred in 17.5% of the sample (n = 1244). The average LOS was 1.4 days (range, 1-91 days; median, 1). There was significant variation in rates of postoperative LOS >1 day across centers (range, 5%-100%; P < .001). Factors independently associated with a postoperative LOS >1 day and their percentage contribution to the prediction model included the need for postoperative intravenous medications for hypertension or hypotension (26%), any major adverse event (MAE) postoperatively (21%), low-volume (<15 CEAs per year) surgeons (28%), increasing age (7%), female gender (4%), positive result on a preoperative stress test (3%), preoperative major stroke ≤30 days (2%), medication-dependent diabetes (1%), severe chronic obstructive pulmonary disease (1%), history of congestive heart failure (1%), and CEA performed on Friday (2%). CONCLUSIONS: Certain patient characteristics predispose to a postoperative LOS >1 day after elective CEA. However, patient characteristics play only a modest (17%) role in determining LOS. The need for postoperative blood pressure control and MAEs are the biggest drivers of postoperative LOS >1 day, but system factors, such as low operative volume, contribute substantially to postoperative LOS >1 day, independent of MAEs. These findings can be used to guide quality improvement efforts designed to reduce LOS after elective CEA.

High-speed fluidic processing circuits for dynamic control of haptic and robotic systems.

Fluidic logic circuits simplify system design for soft robotics by eliminating bulky components while enabling operation in a range of hostile environments that are incompatible with electronics but at the expense of limited computational capabilities and response times on the order of seconds. This paper presents a four-terminal fluidic transistor optimized for fast switching times, reduced component count, low unit cost, and high reproducibility to achieve complex fluidic control circuits while maintaining flow rates of liters per minute. A ring oscillator using three fluidic transistors achieves oscillation frequencies up to a kilohertz with full signal propagation, tolerating billions of cycles without failure. Fundamental processor circuits like a full adder and a 3-bit analog-to-digital converter require just seven transistors each. A decode circuit drives a high-resolution soft haptic display with refresh times below the human perception threshold for latency, and an electronics-free control circuit performs closed-loop position control of a pneumatic actuator with disturbance rejection, demonstrating the value across domains.

Shared quality data are associated with increased protamine use and reduced bleeding complications after carotid endarterectomy in the Vascular Study Group of New England.

OBJECTIVE: The goal of this study was to evaluate whether protamine usage after carotid endarterectomy (CEA) increased within the Vascular Study Group of New England (VSGNE) in response to studies indicating that protamine reduces bleeding complications associated with CEA without increasing the risk of stroke. METHODS: We reviewed 10,059 CEAs, excluding concomitant coronary bypass, performed within the VSGNE from January 2003 to July 2012. Protamine use and reoperation for bleeding were evaluated monthly using statistical process control. Twelve centers and 77 surgeons entering the VSGNE between 2003 and 2008 were classified as original participants, and 14 centers and 60 surgeons joining after May 2009 were considered new. Protamine use for surgeons was categorized as rare (<10%), selective (10%-80%), or routine (>80%). Outcome measures were in-hospital reoperation for bleeding, postoperative myocardial infarction (POMI), and stroke or death. RESULTS: Two significant increases occurred in protamine use for all VSGNE centers over time. From 2003 to 2007, the protamine rate remained stable at 43%. In 2008, protamine usage increased to 52% (P < .01), coincident with new centers joining the VSGNE. Protamine usage then increased to 62% in 2010 (P < .01), shortly after the presentations of the data showing a benefit of protamine. This effect was due to 10 surgeons in the original VSGNE centers who increased their usage of protamine: six surgeons from rare use to selective use and four surgeons to routine use. Reoperation for bleeding was reduced by 0.84% (relative risk reduction, 57.2%) in patients who received protamine (0.6% vs 1.44%; P < .001). There were no differences in POMI (1.1% vs 1.09%) or stroke or death (1.1% vs 1.03%) between protamine treated and untreated patients, respectively. Reoperation for bleeding was decreased for surgeons who used protamine routinely (0.5%; P < .001) compared with selective (1.4%) and rare users (1.5%) of protamine. There were no differences in POMI (0.9%, 1.2%, 1.1%; P = .720) and stroke or death rates (1.0%, 1.2%, 1.0%; P = .656) for rare, selective, and routine users of protamine. CONCLUSIONS: Protamine use increased over time by VSGNE surgeons, most significantly after the presentations of VSGNE-derived data showing the benefit of protamine, and was associated with a decrease in reoperation for bleeding. Improvements in processes of care and outcomes can be achieved in regional quality groups by sharing safety and efficacy data.

Variation in smoking cessation after vascular operations.

OBJECTIVE: Smoking is the most important modifiable risk factor for patients with vascular disease. The purpose of this study was to examine smoking cessation rates after vascular procedures and delineate factors predictive of postoperative smoking cessation. METHODS: The Vascular Study Group of New England registry was used to analyze smoking status preoperatively and at 1 year after carotid endarterectomy, carotid artery stenting, lower extremity bypass, and open and endovascular abdominal aortic aneurysm repair between 2003 and 2009. Of 10,734 surviving patients after one of these procedures, 1755 (16%) were lost to follow-up and 1172 (11%) lacked documentation of their smoking status at follow-up. The remaining 7807 patients (73%) were available for analysis. Patient factors independently associated with smoking cessation were determined using multivariate analysis. The relative contribution of patient and procedure factors including treatment center were measured by χ-pie analysis. Variation between treatment centers was further evaluated by calculating expected rates of cessation and by analysis of means. Vascular Study Group of New England surgeons were surveyed regarding their smoking cessation techniques (85% response rate). RESULTS: At the time of their procedure, 2606 of 7807 patients (33%) were self-reported current smokers. Of these, 1177 (45%) quit within the first year of surgery, with significant variation by procedure type (open abdominal aortic aneurysm repair, 50%; endovascular repair, 49%; lower extremity bypass, 46%; carotid endarterectomy, 43%; carotid artery stenting, 27%). In addition to higher smoking cessation rates with more invasive procedures, age >70 years (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.30-2.76; P < .001) and dialysis dependence (OR, 2.38; 95% CI, 1.04-5.43; P = .04) were independently associated with smoking cessation, whereas hypertension (OR, 1.23; 95% CI, 1.00-1.51; P = .051) demonstrated a trend toward significance. Treatment center was the greatest contributor to smoking cessation, and there was broad variation in smoking cessation rates, from 28% to 62%, between treatment centers. Cessation rates were higher than expected in three centers and significantly lower than expected in two centers. Among survey respondents, 78% offered pharmacologic therapy or referral to a smoking cessation specialist, or both. The smoking cessation rate for patients of these surgeons was 48% compared with 33% in those who did not offer medications or referral (P < .001). CONCLUSIONS: Patients frequently quit smoking after vascular surgery, and multiple patient-related and procedure-related factors contribute to cessation. However, we note significant influence of treatment center on cessation as well as broad variation in cessation rates between treatment centers. This variation indicates an opportunity for vascular surgeons to impact smoking cessation at the time of surgery.

Use of a postoperative insulin protocol decreases wound infection in diabetics undergoing lower extremity bypass.

OBJECTIVE: Strict glucose control in patients undergoing coronary bypass grafting has been shown to decrease infectious complications, arrhythmias, and mortality. Our objective was to determine if strict glucose control reduced morbidity after lower extremity bypass (LEB). METHODS: A prospective pilot study at a single institution within the Vascular Study Group of New England was conducted from January 2009 to December 2010. Patients with diabetes and without undergoing LEB were placed on an intravenous (IV) insulin infusion for 3 days after surgery with titration of blood glucose from 80 to 150 mg/dL. The IV insulin study group (n = 104) was compared to a historic control group (n = 189) that received standard insulin treatment from the preceding 3 years. The Fisher exact test, t-tests, Wilcoxon rank-sum tests, χ(2), and logistic regression analyses were used to compare in-hospital morbidity. Stratified analyses were conducted to determine if findings differed based on the presence or absence of diabetes. RESULTS: There was no difference in postoperative complications between the two groups with regard to graft infection, myocardial infarction, dysrhythmia, primary patency at discharge, or mortality. Patients in the IV insulin group had significantly fewer in-hospital wound infections (4% vs 11%; odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.96; P = .047). This association strengthened after adjusting for potentially confounding baseline differences in gender, body mass index, and smoking status (adjusted OR, 0.22; 95% CI, 0.05-0.84; P = .03). When stratified by presence of diabetes, wound infections were decreased in the IV insulin group (0/44 [0%] vs 9/90 [10%]; P = .03). In patients without diabetes treated with IV insulin, there was no significant difference in wound infections (7% vs 12%; P = .42). CONCLUSIONS: Strict glucose control with a postoperative insulin infusion protocol significantly decreased the incidence of postoperative in-hospital wound infection in the diabetic population. These previously unreported findings from this single-institution prospective study warrant further investigation.

The impact of diabetes on postoperative outcomes following lower-extremity bypass surgery.

OBJECTIVE: The effect of diabetes type (noninsulin dependent vs insulin dependent) on outcomes after lower-extremity bypass (LEB) has not been clearly defined. Therefore, we analyzed associations between diabetes type and outcomes after LEB in patients with critical limb ischemia. METHODS: We performed a retrospective analysis of 1977 infrainguinal LEB operations done for critical limb ischemia between 2003 and 2010 within the Vascular Study Group of New England. Patients were categorized as nondiabetic (ND), noninsulin-dependent diabetic (NIDD), or insulin-dependent diabetic (IDD) based on their preoperative medication regimen. Our main outcome measures were in-hospital mortality and major adverse events (MAEs)--a composite outcome, including myocardial infarction, dysrhythmia, congestive heart failure, wound infection, renal insufficiency, and major amputation. We compared crude and adjusted rates of mortality and MAEs using logistic regression across diabetes categories. RESULTS: Overall, 41% of patients were ND, 28% were NIDD, and 31% were IDD. Crude rates of in-hospital mortality were similar across these groups (1.7% vs 3.1% vs 2.1%; P = .211). Adjusted analyses accounting for differences in patient characteristics showed that diabetes is not associated with increased risk of in-hospital mortality. However, type of diabetes was associated with a higher risk of MAEs in both crude (15.1% for ND; 21.1% for NIDD; and 25.2% for IDD; P < .001) and adjusted analyses (odds ratio for NIDD, 1.41; 95% confidence interval, 1.2-1.7; odds ratio for IDD, 1.53; 95% confidence interval, 1.3-1.8). CONCLUSIONS: Diabetes is a significant contributor to the risk of postoperative complications after LEB surgery, and insulin dependence is associated with higher risk. Quality measures aimed at limiting complications after LEB may have the most impact if these initiatives are focused on patients who are IDD.

Warfarin thromboprophylaxis in cancer patients with central venous catheters (WARP): an open-label randomised trial.

BACKGROUND: The role and dose of anticoagulants in thromboprophylaxis for patients with cancer receiving chemotherapy through central venous catheters (CVCs) is controversial. We therefore assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin and whether the dose of warfarin determines the thromboprophylactic effect. METHODS: In 68 clinical centres in the UK, we randomly assigned 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs to no warfarin, fixed-dose warfarin 1 mg per day, or dose-adjusted warfarin per day to maintain an international normalised ratio between 1.5 and 2.0. Clinicians who were certain of the benefit of warfarin randomly assigned patients to fixed-dose or dose-adjusted warfarin groups. The primary outcome was the rate of radiologically proven, symptomatic catheter-related thrombosis. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN 50312145. FINDINGS: Compared with no warfarin (n=404), warfarin (n=408; 324 [79%] on fixed-dose and 84 [21%] on dose-adjusted) did not reduce the rate of catheter-related thromboses (24 [6%] vs 24 [6%]; relative risk 0.99, 95% CI 0.57-1.72, p=0.98). However, compared with fixed-dose warfarin (n=471), dose-adjusted warfarin (n=473) was superior in the prevention of catheter-related thromboses (13 [3%] vs 34 [7%]; 0.38, 0.20-0.71, p=0.002). Major bleeding events were rare; an excess was noted with warfarin compared with no warfarin (7 vs 1, p=0.07) and with dose-adjusted warfarin compared with fixed-dose warfarin (16 vs 7, p=0.09). A combined endpoint of thromboses and major bleeding showed no difference between comparisons. We did not note a survival benefit in either comparison. INTERPRETATION: The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter-related or other thromboses in patients with cancer and therefore we should consider newer treatments. FUNDING: Medical Research Council and Cancer Research UK.

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer.

BACKGROUND: Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. METHODS: All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. RESULTS: The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P=0.04). Analysis of the Antiplatelet Trialists' Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P=0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P=0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. CONCLUSIONS: Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months' duration. (Current Controlled Trials number, ISRCTN98278138 [controlled-trials.com].).

Factors associated with death 1 year after lower extremity bypass in Northern New England.

BACKGROUND: Using 30-day operative mortality reported with lower extremity bypass (LEB) in preoperative decision making may underestimate the actual death rate encountered before patients have truly recovered from surgery, especially in elderly, debilitated patients with significant tissue loss. Therefore, we examined preoperative, patient-level risk factors that predict survival within the first year following LEB. METHODS: Using our regional quality improvement initiative in 11 hospitals in Northern New England, we studied 2306 LEB procedures performed in 2031 patients between January 2003 and December 2007. Sixty surgeons contributed to our database, and over 100 demographic and clinical variables were abstracted by trained researchers. Cox proportional hazards models were used to generate hazard ratios (HR) and surrounding 95% confidence intervals (CI) for our combined outcome measure of death occurring within the first year postoperatively. RESULTS: We found that within our cohort of 2306 bypass procedures, 11% of patients died within 1 year of surgery (2% prior to discharge, 9% prior to 1-year follow-up). We identified six preoperative patient characteristics associated with higher risk of death in multivariate analysis: congestive heart failure (HR 1.3, 95% CI 1.0-1.8), diabetes (HR 1.5, 95% CI 1.1-2.1), critical limb ischemia (CLI) (HR 1.7, 95% CI 1.3-2.4), lack of single-segment saphenous vein (HR 1.9, 95% CI 1.5-2/5), age over 80 (HR 2.0, 95% CI 1.5-2.7), dialysis dependence (HR 2.7, 95% CI 1.9-3.6), and emergent nature of the procedure (HR 3.4, 95% CI 1.7-6.8). While patients with no risk factors had 1-year death rates that were less than 5%: patients with three or more risk factors had a 28% chance of dying before 1 year postoperatively. When we compared risk-adjusted survival across centers, we found that one center in our region performed significantly better than expected (observed-to-expected outcome ratio 0.7, 95% CI 0.6-0.9, P = .04). CONCLUSIONS: Preoperative risk factors allow surgeons to predict survival in the first year following LEB, and to more precisely inform patients about their operative risk with LEB. Additionally, our model facilitates benchmarking comparison of risk-adjusted outcomes across our region. We believe quality improvement measures such as these will allow surgeons to identify best practices and thereby improve outcomes with LEB across centers.

Factors associated with amputation or graft occlusion one year after lower extremity bypass in northern New England.

BACKGROUND: Optimal patient selection for lower extremity bypass surgery requires surgeons to predict which patients will have durable functional outcomes following revascularization. Therefore, we examined risk factors that predict amputation or graft occlusion within the first year following lower extremity bypass. METHODS: Using our regional quality-improvement initiative in 11 hospitals in northern New England, we studied 2,306 lower extremity bypass procedures performed in 2,031 patients between January 2003 and December 2007. Sixty surgeons contributed to our database, and over 100 demographic and clinical variables were abstracted by trained researchers. Cox proportional hazards models were used to generate hazard ratios and surrounding 95% confidence intervals (CIs) for our combined outcome measure of major amputation (above-knee or below-knee) or permanent graft occlusion (loss of secondary patency) occurring within the first year postoperatively. RESULTS: We found that within our cohort of 2,306 bypass procedures 17% resulted in an amputation or graft occlusion within 1 year of surgery. Of the 143 amputations performed (8% of all limbs undergoing bypasses), 17% occurred in the setting of a patent graft. Similarly, of the 277 graft occlusions (12% of all bypasses), 42% resulted in a major amputation. We identified eight preoperative patient characteristics associated with amputation or graft occlusion in multivariate analysis: age <50, nonambulatory status preoperatively, dialysis dependence, diabetes, critical limb ischemia, need for venovenostomy, tarsal target, and living preoperatively in a nursing home. While patients with no risk factors had 1-year amputation/occlusion rates that were <1%, patients with three or more risk factors had a nearly 30% chance of suffering amputation or graft occlusion by 1 year postoperatively. When we compared risk-adjusted rates of amputation/occlusion across centers, we found that one center in our region performed significantly better than expected (observed/expected ratio 0.7, 95% CI 0.6-0.9, p < 0.04). CONCLUSION: Preoperative risk factors allow surgeons to predict the risk of amputation or graft occlusion following lower extremity bypass and to more precisely inform patients about their operative risk and functional outcomes. Additionally, our model facilitates comparison of risk-adjusted outcomes across our region. We believe quality-improvement measures such as these will allow surgeons to identify best practices and thereby improve outcomes across centers.

Study protocol: national research partnership to improve primary health care performance and outcomes for Indigenous peoples.

BACKGROUND: Strengthening primary health care is critical to reducing health inequity between Indigenous and non-Indigenous Australians. The Audit and Best practice for Chronic Disease Extension (ABCDE) project has facilitated the implementation of modern Continuous Quality Improvement (CQI) approaches in Indigenous community health care centres across Australia. The project demonstrated improvements in health centre systems, delivery of primary care services and in patient intermediate outcomes. It has also highlighted substantial variation in quality of care. Through a partnership between academic researchers, service providers and policy makers, we are now implementing a study which aims to 1) explore the factors associated with variation in clinical performance; 2) examine specific strategies that have been effective in improving primary care clinical performance; and 3) work with health service staff, management and policy makers to enhance the effective implementation of successful strategies. METHODS/DESIGN: The study will be conducted in Indigenous community health centres from at least six States/Territories (Northern Territory, Western Australia, New South Wales, South Australia, Queensland and Victoria) over a five year period. A research hub will be established in each region to support collection and reporting of quantitative and qualitative clinical and health centre system performance data, to investigate factors affecting variation in quality of care and to facilitate effective translation of research evidence into policy and practice. The project is supported by a web-based information system, providing automated analysis and reporting of clinical care performance to health centre staff and management. DISCUSSION: By linking researchers directly to users of research (service providers, managers and policy makers), the partnership is well placed to generate new knowledge on effective strategies for improving the quality of primary health care and fostering effective and efficient exchange and use of data and information among service providers and policy makers to achieve evidence-based resource allocation, service planning, system development, and improvements of service delivery and Indigenous health outcomes.

Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer.

BACKGROUND: The National Epirubicin Adjuvant Trial (NEAT) and the BR9601 trial examined the efficacy of anthracyclines in the adjuvant treatment of early breast cancer. METHODS: In NEAT, we compared four cycles of epirubicin followed by four cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) with six cycles of CMF alone. In the BR9601 trial, we compared four cycles of epirubicin followed by four cycles of CMF, with eight cycles of CMF alone every 3 weeks. The primary end points were relapse-free and overall survival. The secondary end points were adverse effects, dose intensity, and quality of life. RESULTS: The two trials included 2391 women with early breast cancer; the median follow-up was 48 months. Relapse-free and overall survival rates were significantly higher in the epirubicin-CMF groups than in the CMF-alone groups (2-year relapse-free survival, 91% vs. 85%; 5-year relapse-free survival, 76% vs. 69%; 2-year overall survival, 95% vs. 92%; 5-year overall survival, 82% vs. 75%; P<0.001 by the log-rank test for all comparisons). Hazard ratios for relapse (or death without relapse) (0.69; 95% confidence interval [CI], 0.58 to 0.82; P<0.001) and death from any cause (0.67; 95% CI, 0.55 to 0.82; P<0.001) favored epirubicin plus CMF over CMF alone. Independent prognostic factors were nodal status, tumor grade, tumor size, and estrogen-receptor status (P<0.001 for all four factors) and the presence or absence of vascular or lymphatic invasion (P=0.01). These factors did not significantly interact with the effect of epirubicin plus CMF. The overall incidence of adverse effects was significantly higher with epirubicin plus CMF than with CMF alone but did not significantly affect the delivered-dose intensity or the quality of life. CONCLUSIONS: Epirubicin plus CMF is superior to CMF alone as adjuvant treatment for early breast cancer. (ClinicalTrials.gov number, NCT00003577 [ClinicalTrials.gov].).

Not all deep vein thrombosis is created equal: Incidence of preexisting chronic deep vein thrombosis among high-risk traumatized patients.

BACKGROUND: Traumatized patients are at risk of developing deep vein thrombosis (DVT) and DVT prophylaxis is the standard of care. The Centers for Medicare and Medicaid Services classifies DVT as a hospital-acquired condition and can deny payment for treatment of DVT and, in addition, place financial penalties on hospitals with higher than acceptable rates of DVT, unless the DVT was preexisting. We sought to determine the rate of preexisting chronic DVT among symptomatic traumatized inpatients at our ACS-verified Level 1 trauma center. METHODS: Retrospective review of all traumatized patients admitted for >48 hours over a 7-year study period ending December 2016. Patients who had undergone lower extremity duplex ultrasound (LEDUS) were reviewed further to evaluate the results of these tests. Patients were classified as having either no DVT, acute DVT, or chronic (preexisting) DVT based on sonographic characteristics. Incidence, patient demographics, injury severity and outcomes were compared for patients with and without DVT and also for patients with acute and chronic DVT. RESULTS: Five thousand five hundred forty-three patients met inclusion criteria. Of those, 391 (7.0%) had undergone at least one LEDUS for suspicion of DVT. Deep vein thrombosis was diagnosed in 64 (16%) of the patients undergoing LEDUS and thus 1.1% of the entire population had symptomatic DVT diagnosed during admission. Of the 64 patients with DVT, sonographic characteristics classified 56 (87.5%) as "acute." 6 (9%) as "chronic" (preexisting) and 2 (3.5%) as "indeterminate." Among the six patients found to have a preexisting DVT only three (50%) acknowledged a history of DVT. CONCLUSION: In the absence of routine DVT surveillance almost 10% of traumatized patients diagnosed with DVT likely have chronic preexisting DVT that is unknown to the patient in 50% of cases. This has significant financial implications for hospitals. LEVEL OF EVIDENCE: Epidemiologic/Prognostic, level III.

Use of the Lean Manufacturing Principles to Improve Total Parenteral Nutrition Logistics and Clinical Outcomes in the Neonatal Patient Population.

Total parenteral nutrition (TPN) is one of the most frequently used pharmaceuticals administered to patients in our Neonatal Intensive Care Unit (NICU). Initially, the total interdepartmental processing time (ordering, manufacturing, and delivery between NICU and Pharmacy) averaged 15.2 hours. Inefficiencies in this process only allowed TPN to infuse 8.8 hours on average before labs were collected the next morning. Given the short administration-to-laboratory collection time, we hypothesized that laboratory samples would not adequately reflect the effect of the current TPN infusion. Furthermore, clinicians would be making decisions based on suboptimal data and ultimately nourish this patient population inadequately. METHODS: The project team and the frontline staff created an efficient process for the manufacture and delivery of TPN. They removed waste in the process associated with manufacturing TPN and created capacity for change upstream (ordering process) and downstream (TPN infusion process) of the internal pharmacy process. The use of selection criteria and new standard operating procedures allowed for controlled PDSA testing of changes on a subset of patients. After we attained proven, sustainable results, we scaled the improvement efforts to the entire NICU patient population. RESULTS: After 4 cycles of change, patients now receive TPN on average 14.2 hours before new labs are collected. The interventions over the continuum of this project yielded statistically significant results, increased infusion times to our patients by 61.4% (P < 0.001), improved glucose homeostasis, and decreased average length of stay. CONCLUSIONS: In conclusion, creating process capacity from incremental changes and iterative PDSA cycles has yielded sustained results.

Standardised early warning scores in rural interfacility transfers: A pilot study into their potential as a decision-making aid.

INTRODUCTION: While 12.4% of British Columbians live rurally, only 2.0% of specialists practise rurally, making interfacility transport of high-acuity patients vital. Decision-making aids have been identified as a way to improve the interfacility transfer process. We conducted a pilot study to explore the potential of the Standardised Early Warning Score (SEWS) as a decision-making aid for staff at sending facilities. METHODS: SEWSs were calculated from a database of 418 transfers from sending facilities in rural, small and medium population centres to larger receiving facilities. The SEWSs were compared against one another over time using McNemar's and the Wilcoxon signed-ranks tests. The SEWSs were then tested for their association with six outcomes using Pearson's or Fisher's Chi-squared test and the Mann-Whitney U-test. RESULTS: While at the sending facility, both the number of SEWSs that was four or greater and the average SEWS decreased over time (P < 0.001 for both). A first SEWS of four or greater was predictive of more intervention categories during transport (P = 0.047), an adverse event during transport (P = 0.004), an adverse event within 30 min of arrival at the receiving facility (P = 0.004) and death before discharge from the receiving facility (P = 0.043) but not deterioration during transport, or the length of stay at the receiving facility. CONCLUSION: Overall, the performance of the SEWS in the context of rural interfacility transport suggests that the tool will have utility in supporting decision-making.

Introduction: Alors que 12,4 % des résidents de la Colombie-Britannique vivent en milieu rural, seuls 2,0 % des spécialistes y pratiquent, ce qui rend essentiel le transport entre établissements des patients en état grave. Des outils de prise de décision ont été désignés comme méthode pour améliorer le processus de transfert entre établissements. Dans le cadre d'une étude pilote, nous nous sommes penchés sur le potentiel du score SEWS (Standardised Early Warning Score) comme outil de prise de décision à l'intention du personnel des établissements d'origine. Méthodes: Les scores SEWS ont été calculés dans une banque de données de 418 transferts d'établissements d'origine situés dans des agglomérations rurales de petite et moyenne taille vers des établissements de réception plus importants. Les scores SEWS ont été comparés entre eux dans le temps à l'aide des tests de McNemar et Wilcoxon Signed Ranks. L'association des scores SEWS à six paramètres d'évaluation a ensuite été testée à l'aide des tests de chi carré de Pearson ou de Fisher et du test de Mann-Whitney. Résultats: À l'établissement d'origine, le nombre de scores SEWS de quatre et plus et le score SEWS moyen se sont abaissés dans le temps (p < 0,001 dans les deux cas). Un score SEWS initial de quatre et plus prédisait un plus grand nombre de catégories d'interventions durant le transport (p = 0,047), la survenue d'un événement indésirable durant le transport (p = 0,004), la survenue d'un événement indésirable dans les 30 minutes après l'arrivée à l'établissement de réception (p = 0,004), et le décès avant le congé de l'établissement de réception (p = 0,043), mais il ne prédisait pas la détérioration durant le transport ni la durée du séjour à l'établissement de réception. Conclusion: Dans l'ensemble, le rendement du score SEWS dans le contexte du transport rural entre établissements laisse croire que l'outil serait utile à la prise de décision. Mots-clés: Early Warning Scores, Standardised Early Warning Score, Standardised Early Warning Score rural, transfert entre établissements, transport entre établissements.