Anthony D. Whittemore

Suggested standards for reports dealing with lower extremity ischemia

Reports in the vascular surgery literature are often difficult to assess and compare with each other because of poorly defined terms, imprecise categorization, lack of indices for gauging the severity of the disease or the presence of risk factors capable of affecting outcome, and varying criteria for success or failure--in essence, a lack of standardized reporting practices. The joint councils of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery have appointed an ad hoc committee to deal with this problem. This report represents the recommendations of the first of its several subcommittees, that is, the one dealing with reports on lower extremity ischemia. Certain terms are defined and criteria offered for uniformly gauging the severity of disease, the findings of diagnostic studies, the types of therapeutic interventions, and the outcome of such treatments. Although future modifications may further improve on this effort, it is hoped that this committees recommendations will help establish reporting standards for articles dealing with lower extremity ischemia.

GUIDELINES FOR CAROTID ENDARTERECTOMY: A STATEMENT FOR HEALTHCARE PROFESSIONALS FROM A SPECIAL WRITING GROUP OF THE STROKE COUNCIL, AMERICAN HEART ASSOCIATION

Since the 1950s carotid endarterectomy has been performed in patients with symptomatic carotid artery stenosis, based on suggestive but inconclusive evidence for its effectiveness. Only during the last 5 years have randomized studies clarified the indications for surgery. In preparing this report, panel members used the same rules of evidence used in the previous report1 2 (Table⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations Few studies have analyzed control of risk factors in a randomized, prospective manner following carotid endarterectomy. However, a wealth of data are available regarding the general relationship between risk factor control and stroke risk. These data provide some guidance for the care of endarterectomy patients. ### Hypertension Hypertension is the most powerful, prevalent, and treatable risk factor for stroke.3 Both systolic and diastolic blood pressure are independently related to stroke incidence. Isolated systolic hypertension, which is common in the elderly, also considerably increases risk of stroke. Reduction of elevated blood pressure significantly lowers risk of stroke. Meta-analyses of randomized trials found that an average reduction in diastolic blood pressure of 6 mm Hg produces a 42% reduction in stroke incidence.3 4 Treatment of isolated systolic hypertension in people older than 60 years also reduces stroke incidence by 36% without an excessive number of side effects such as depression or dementia.5 Long-term care of patients after endarterectomy should include careful control of hypertension (Grade A recommendation for treatment of hypertension in general; Grade C recommendation for postendarterectomy care). Perioperative treatment of hypertension after carotid endarterectomy represents a special situation. Poor control of blood pressure after endarterectomy increases risk of cerebral hyperperfusion syndrome.6 7 8 9 This complication is characterized by unilateral headache, seizures, and occasionally altered mental status or focal neurological signs. Neuroimaging may show intracerebral hemorrhages10 11 12 or white …

Vascular access for hemodialysis. Patency rates and results of revision.

Over a 4-year interval, 324 arteriovenous conduits were created in 256 patients with end-stage renal disease as access for chronic hemodialysis. These included 154 Cimino fistulae, 163 polytetrafluoroethylene (PTFE) grafts, and seven miscellaneous grafts. Satisfactory patency rates were demonstrated for as long as 4 years for both Cimino fistulae and PTFE grafts by life-table analysis. Failures of Cimino fistulae usually occurred early in the postoperative period, secondary to attempts to use inadequate veins. Thrombosis caused the majority of PTFE graft failures and was generally the result of venous stenosis. Correction of such venous stenosis is mandatory to restore graft patency and can result in prolonged graft survival.

Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial

BACKGROUND Cell-cycle blockade by ex-vivo gene therapy of experimental vein grafts inhibits the neointimal hyperplasia and subsequent accelerated atherosclerosis that lead to human bypass-graft failure. In a prospective, randomised, controlled trial, we investigated the safety and biological efficacy of intraoperative gene therapy in patients receiving bypass vein grafts. METHODS We studied gene therapy that uses decoy oligodeoxynucleotide, which binds and inactivates the pivotal cell-cycle transcription factor E2F. 41 patients were randomly assigned untreated (16), E2F-decoy-treated (17), or scrambled-oligodeoxynucleotide-treated (eight) human infrainguinal vein grafts. Oligonucleotide was delivered to grafts intraoperatively by ex-vivo pressure-mediated transfection. The primary endpoints were safety and inhibition of target cell-cycle regulatory genes and of DNA synthesis in the grafts. Analysis was by intention to treat. FINDINGS Mean transfection efficiency was 89.0% (SD 1.9). Proliferating-cell nuclear antigen and c-myc mRNA concentrations and bromodeoxyuridine incorporation were decreased in the EF2-decoy group by medians of 73% [IQR 53-84], 70% [50-79], and 74% [56-83], respectively) but not in the scrambled-oligodeoxynucleotide group (p<0.0001). Groups did not differ for postoperative complication rates. At 12 months, fewer graft occlusions, revisions, or critical stenoses were seen in the E2F-decoy group than in the untreated group (hazard ratio 0.34 [95% CI 0.12-0.99]). INTERPRETATION Intraoperative transfection of human bypass vein grafts with E2F-decoy oligodeoxynucleotide is safe, feasible, and can achieve sequence-specific inhibition of cell-cycle gene expression and DNA replication. Application of this genetic-engineering strategy may lower failure rates of human primary bypass vein grafting.

Correlation between Preoperative Ischemia and Major Cardiac Events after Peripheral Vascular Surgery

Patients who undergo peripheral vascular surgery are at increased risk for postoperative cardiac events and are difficult to assess preoperatively because of limitations on their activity. We prospectively studied 176 consecutive eligible patients undergoing elective vascular surgery to determine the value in predicting a postoperative cardiac event of preoperative electrocardiographic monitoring to detect myocardial ischemia. Of the 176 patients, 32 (18 percent) had 75 episodes of monitored ischemic ST-segment depression preoperatively (of which 73 were asymptomatic), and 13 (7 percent) met strict criteria for major postoperative cardiac events, including 1 with a fatal myocardial infarction, 3 with nonfatal infarctions, 4 with unstable angina, and 5 with ischemic pulmonary edema. Of the 32 patients with ischemia before their operations, 12 had postoperative events (univariate relative risk, 54; 95 percent confidence interval, 7.2 to 400). Only 1 postoperative event occurred among 144 patients who did not have preoperative ischemia. The sensitivity of preoperative ischemia was 92 percent, the specificity 88 percent, the predictive value of a positive result 38 percent, and the predictive value of a negative result 99 percent. In multivariate analyses, preoperative ischemia was the most significant correlate of postoperative cardiac events and remained a statistically significant independent correlate even after we had controlled for all other preoperative factors (multivariate relative risk, 24.4; 95 percent confidence interval, 6.8 to 88). These preliminary data suggest that preoperative electrocardiographic monitoring to detect episodes of myocardial ischemia is a useful method for assessing cardiac risk in patients who undergo elective vascular surgery. In particular, the absence of ischemia during monitoring indicates a very low risk.

Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms.

BACKGROUND Thinning of the tunica media and rarefaction of smooth muscle cells (SMCs) characterize aneurysmal aortas. Apoptosis determines the cellularity and morphogenesis of tissue. Macrophages and T lymphocytes infiltrate the wall of abdominal aortic aneurysms (AAAs) and produce death-promoting proteins (perforin, Fas, and FasL). This study investigated whether apoptosis occurs in association with the expression of these proteins. METHODS AND RESULTS We examined signs of apoptosis and expression of death-promoting mediators in segments of AAAs from patients undergoing elective repair (n=20). Anti-alpha-actin immunostaining showed a reduced number of SMCs in AAAs. In situ terminal transferase-mediated dUTP nick end-labeling (TUNEL) showed higher levels of DNA fragmentation in AAAs than in controls (n=5). The AAA walls contained more cells bearing markers of apoptosis than normal aorta (P<0.05, Students t test). Double immunostaining identified SMCs and macrophages as the principal cell types displaying fragmented DNA. Immunohistochemistry revealed that AAAs but not normal aorta contained CD4(+) and CD8(+) T cells that expressed well-characterized cytotoxic mediators: perforin, which produces membrane damage, and Fas, which acts by ligand-receptor interaction. Double immunostaining also identified SMCs that expressed Fas. Immunoblotting confirmed the presence and, in the case of Fas, activation of these proteins in aneurysmal tissue. CONCLUSIONS Many medial SMCs in AAAs bear markers of apoptosis and signals capable of initiating cell death. Apoptotic death may contribute to the reduction of cellularity and to the impaired repair and maintenance of the arterial extracellular matrix in AAAs. Macrophages and T lymphocytes infiltrate the wall of AAAs, where they can produce cytotoxic mediators such as cytokines, perforin, and Fas/FasL. These death-promoting products of activated immune cells may contribute to elimination of SMCs, a source of elastin and collagen, during the pathogenesis of AAAs.

Effect of bar-code technology on the safety of medication administration.

BACKGROUND Serious medication errors are common in hospitals and often occur during order transcription or administration of medication. To help prevent such errors, technology has been developed to verify medications by incorporating bar-code verification technology within an electronic medication-administration system (bar-code eMAR). METHODS We conducted a before-and-after, quasi-experimental study in an academic medical center that was implementing the bar-code eMAR. We assessed rates of errors in order transcription and medication administration on units before and after implementation of the bar-code eMAR. Errors that involved early or late administration of medications were classified as timing errors and all others as nontiming errors. Two clinicians reviewed the errors to determine their potential to harm patients and classified those that could be harmful as potential adverse drug events. RESULTS We observed 14,041 medication administrations and reviewed 3082 order transcriptions. Observers noted 776 nontiming errors in medication administration on units that did not use the bar-code eMAR (an 11.5% error rate) versus 495 such errors on units that did use it (a 6.8% error rate)--a 41.4% relative reduction in errors (P<0.001). The rate of potential adverse drug events (other than those associated with timing errors) fell from 3.1% without the use of the bar-code eMAR to 1.6% with its use, representing a 50.8% relative reduction (P<0.001). The rate of timing errors in medication administration fell by 27.3% (P<0.001), but the rate of potential adverse drug events associated with timing errors did not change significantly. Transcription errors occurred at a rate of 6.1% on units that did not use the bar-code eMAR but were completely eliminated on units that did use it. CONCLUSIONS Use of the bar-code eMAR substantially reduced the rate of errors in order transcription and in medication administration as well as potential adverse drug events, although it did not eliminate such errors. Our data show that the bar-code eMAR is an important intervention to improve medication safety. (ClinicalTrials.gov number, NCT00243373.)

Evidence for Altered Balance Between Matrix Metalloproteinases and Their Inhibitors in Human Aortic Diseases

BACKGROUND Although abdominal aortic aneurysms (AAAs) exhibit increased expression of matrix metalloproteinases (MMPs), the functional balance between MMPs and their tissue inhibitors (TIMPs) remains uncertain. This report compares the proteolytic activity in normal aorta, aorto-occlusive disease (AOD), and AAA by use of a novel in situ zymographic technique. METHODS AND RESULTS Infrarenal aortic specimens were obtained from 25 patients undergoing surgery for AOD or AAA and were compared with normal aortic tissue (n = 7) obtained from cadavers. Immunohistochemical staining was performed for collagenase (MMP-1), gelatinase A (MMP-2), stromelysin (MMP-3), TIMP-1, and TIMP-2. Net proteolytic activity was determined with in situ zymography whereby aortic sections were incubated on fluorescently labeled substrate. Proteolytic activity was detected under epifluorescent examination. Compared with normal aortic tissue, AOD and AAA tissue demonstrated marked increases in MMP-1 and MMP-3 immunoreactivity, predominantly in the neointima, and modest increases in TIMP-1. MMP-2 was increased in the diseased aortas, and TIMP-2 was abundant in normal, AOD, and AAA samples. Zymography revealed proteolytic activity in AOD and AAA tissues with active digestion of casein and gelatin substrate, particularly on the luminal portion of the specimens. Normal specimens exhibited no lytic activity. Comparison of AOD and AAA specimens revealed no difference in MMP/TIMP immunoreactivity or net proteolytic activity. CONCLUSIONS MMP expression is markedly increased in AOD and AAA samples, and an imbalance between MMPs and their inhibitors results in similar proteolytic activity. The eventual formation of aneurysmal or occlusive lesions appears not to result from an ongoing difference in the proteolytic pattern.

Medication Dispensing Errors and Potential Adverse Drug Events before and after Implementing Bar Code Technology in the Pharmacy

Context Bar code technology could help reduce medication dispensing errors in the pharmacy. Contribution The authors observed hospital pharmacy technicians as they dispensed medications before and after the installation of a storage and retrieval system that used bar code technology to label medications. After implementation of the bar codebased system, dispensing errors were much less frequent if the system required scanning of all dispensed doses. Some errors actually increased if the system did not require scanning every dose. Cautions Bar code technology was only one part of an entirely redesigned medication storage and dispensing system. Implications Properly implemented, medication storage and dispensing systems that use bar code technology may help to reduce medication dispensing errors. The Editors Medication errors in hospitals are common (1, 2), and dispensing errors made in the pharmacy contribute considerably to these errors (3). Overall, dispensing error rates are relatively low, but because of the high volume of medications dispensed, more than 100 undetected dispensing errors may occur in a busy hospital pharmacy every day (4). Because only about one third of these dispensing errors are intercepted by nurses before medication administration (3), many errors reach hospitalized patients (5). Therefore, dispensing errors are an important target for patient safety interventions. Bar code technology has been touted as a promising strategy to prevent medication errors (6, 7). In industries outside of health care, bar code technology has been widely adopted because of its ease of use and high degree of reliability. In the context of pharmacy dispensing, if all medications in the pharmacy had a bar code that is scanned to ensure that the correct medication in its correct dose and formulation is being dispensed, dispensing errors may be substantially reduced. On the basis of the theoretical benefits for patient safety, the U.S. Food and Drug Administration (FDA) has mandated bar codes for all medications used in hospitals by April 2006 (8), and many institutions are beginning to adopt this technology to increase the accuracy of the dispensing and administration processes. Despite enthusiasm for this technology, few published studies have evaluated the effect of bar code technology on dispensing errors (9, 10). Previous work has also demonstrated that the implementation of health information technology (HIT) may result in unintended consequences and new types of errors (1113). Therefore, the decision to adopt this technology must be informed by a careful evaluation of its efficacy and limitations. To that end, we evaluated a recent implementation of bar code technology in a large hospital pharmacy to measure the changes in the rates of dispensing errors (see Glossary) and potential adverse drug events (ADEs) (see Glossary). Methods Study Site and Study Period We performed a before-and-after evaluation study over a 20-month period in a 735-bed tertiary care academic medical center, where approximately 5.9 million doses of medications were dispensed per year from the central inpatient pharmacy. Between February and August 2003 (prebar code implementation period), we measured the baseline rates of dispensing errors and potential ADEs. In November and December 2003, the hospital pharmacy converted to a bar codeassisted dispensing process. After the conversion, we remeasured the rates of dispensing errors and potential ADEs between May and September 2004 (postbar code implementation period). Observations in both periods were conducted on weekdays during the day shift, when most medications are dispensed. Dispensing Processes during Pre and PostBar Code Implementation Periods The Figure depicts an overview of the medication use process during the 2 observation periods. In both observation periods, the dispensing process involves 3 major steps that are commonly used in approximately 76% of U.S. hospitals (14) (Table 1 and Figure). In the first step, medications delivered to the pharmacy are stocked in the pharmacy inventory. The second step, known as filling, requires a pharmacy technician to retrieve the appropriate medications from the pharmacy inventory. The third step, known as verification, requires a staff pharmacist to verify the accuracy of the medications filled by the technician before delivery to patient care areas. If the staff pharmacist detects a dispensing error, the medication is returned for refilling. While the stocking and filling steps changed extensively with bar code technology implementation, the pharmacists visual inspection step remained functionally unchanged in the postbar code implementation period. In both periods, medications dispensed from the pharmacy would be delivered to either patient-specific medication drawers or semi-automated medication cabinets (Sure-Med, Omnicell, Mountain View, California) on the patient care units. Figure. Overview of the pharmacy dispensing process. *Sure-Med, Omnicell, Mountain View, California. CPOE = computerized physician order entry; MD = physician. Table 1. Description of the Dispensing Processes Studied in the PreBar Code and PostBar Code Implementation Periods In the prebar code implementation period, we studied 3 major dispensing processes: 1) Sure-Med fill, 2) first-dose fill, and 3) cart fill. Each medication dose (see Glossary) was dispensed by only 1 of these processes (Table 1). In the prebar code period, medications were stocked manually onto shelves and the filling step for all 3 processes was performed manually, with the pharmacy technician relying solely on visual inspection to pick the appropriate medication from the several storage areas in the pharmacy inventory. During the bar code conversion process, the study pharmacy built a dedicated repackaging center, which affixed a bar code onto every dose of medication (for example, each individual pill, vial, or ampoule) if the manufacturer had not applied a bar code. In the postbar code period, the prebar code dispensing processes were reorganized into 3 new dispensing processes: 1) carousel fill, 2) alternate zone fill, and 3) 2-day fill (Table 1). Each medication dose was dispensed by only 1 of these processes. For the 3 new dispensing processes, the pharmacy used a different configuration of bar codescanning technology to leverage a combination of internally developed and vendor-supplied software and hardware. Carousel Fill Process The carousel fill process dispensed the compact and nonrefrigeration-requiring forms of commonly used medications for the semi-automated medication cabinets (Sure-Med). These cabinets stored frequently used medications in medication-specific drawers, from which nurses dispensed doses for all patients on a particular unit. The Sure-Med fill process previously dispensed these medications. The new carousel fill process was so named because it used a newly purchased, bar codebased, high-volume storage and retrieval system called the carousel, which also monitored the supply levels in the Sure-Med cabinets to ensure an adequate supply of frequently used medications on each unit. When medications were stocked into the carousel, pharmacy staff scanned 1 dose per batch to ensure that the correct medications were placed in the appropriate compartment. When a pharmacy technician retrieved medications during the filling step, the machine directed the technician to the appropriate storage compartment within the carousel. The technician visually inspected the retrieved medication and scanned the bar code on it to ensure that he or she had retrieved the correct medication. In most cases, the carousel machine would instruct the technician to retrieve several doses of the same medication (a medication batch [see Glossary]) at a time to replenish the supplies for a particular cabinet. In these cases, only 1 dose was scanned. We will use Stock&Retrieve(+) Scan(+) as shorthand to characterize this process (see Glossary). Alternate Zone Process The alternate zone process dispensed commonly used medications that could not be accommodated in the carousel machine because of their size or need for refrigeration. Medications for this process were stocked onto shelves manually. When pharmacy technicians filled medications for this process, they manually retrieved the medications from the shelves, visually inspected them, and scanned their bar codes. Similar to the carousel fill process, if several doses of the same medication were being dispensed, only 1 dose was scanned. We will use Stock&Retrieve() Scan(+) as shorthand to characterize this process (see Glossary). Two-Day Fill Process The 2-day fill process handled less commonly used medications that the first-dose fill and cart fill processes previously dispensed to the patient-specific drawers on patient care units. Medications were stocked manually onto shelves and were retrieved by hand during the filling step. The technician in this process would typically retrieve several doses of the same medication at a time so that the patient-specific drawer in the patient care area would carry a 2-day supply. However, unlike the procedure in the carousel or alternate zone fill process, all doses retrieved in the 2-day fill process had to be scanned. We will use Stock&Retrieve() Scan(++) as shorthand to characterize this process (see Glossary). We excluded one dispensing process, controlled substance fill, which accounted for approximately 16% of daytime, weekday dispensing in the pharmacy, from the study because of limited research personnel and its lower baseline dispensing error rate (4). Measurement of Dispensing Error and Potential ADE Rates The primary outcomes of our study were the rates of target dispensing errors (see Glossary) and target potential ADEs (see Glossary). We used identical methods that were approved by the institutional review board at the study institution to measure the rates of dispensing errors in the prebar

Guidelines for Carotid Endarterectomy A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association

Since the 1950s carotid endarterectomy has been performed in patients with symptomatic carotid artery stenosis, based on suggestive but inconclusive evidence for its effectiveness. Only during the last 5 years have randomized studies clarified the indications for surgery. In preparing this report, panel members used the same rules of evidence used in the previous report1 2 (Table⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations Few studies have analyzed control of risk factors in a randomized, prospective manner following carotid endarterectomy. However, a wealth of data are available regarding the general relationship between risk factor control and stroke risk. These data provide some guidance for the care of endarterectomy patients. ### Hypertension Hypertension is the most powerful, prevalent, and treatable risk factor for stroke.3 Both systolic and diastolic blood pressure are independently related to stroke incidence. Isolated systolic hypertension, which is common in the elderly, also considerably increases risk of stroke. Reduction of elevated blood pressure significantly lowers risk of stroke. Meta-analyses of randomized trials found that an average reduction in diastolic blood pressure of 6 mm Hg produces a 42% reduction in stroke incidence.3 4 Treatment of isolated systolic hypertension in people older than 60 years also reduces stroke incidence by 36% without an excessive number of side effects such as depression or dementia.5 Long-term care of patients after endarterectomy should include careful control of hypertension (Grade A recommendation for treatment of hypertension in general; Grade C recommendation for postendarterectomy care). Perioperative treatment of hypertension after carotid endarterectomy represents a special situation. Poor control of blood pressure after endarterectomy increases risk of cerebral hyperperfusion syndrome.6 7 8 9 This complication is characterized by unilateral headache, seizures, and occasionally altered mental status or focal neurological signs. Neuroimaging may show intracerebral hemorrhages10 11 12 or white …