Innovations in the assessment of transplant center performance: implications for quality improvement.

Continuous quality improvement efforts have become a central focus of leading health care organizations. The transplant community has been a pioneer in periodic review of clinical outcomes to ensure the optimal use of limited donor organs. Through data collected from the Organ Procurement and Transplantation Network (OPTN) and analyzed by the Scientific Registry of Transplant Recipients (SRTR), transplantation professionals have intermittent access to specific, accurate and clinically relevant data that provides information to improve transplantation. Statistical process control techniques, including cumulative sum charts (CUSUM), are designed to provide continuous, real-time assessment of clinical outcomes. Through the use of currently collected data, CUSUMs can be constructed that provide risk-adjusted program-specific data to inform quality improvement programs. When retrospectively compared to currently available data reporting, the CUSUM method was found to detect clinically significant changes in center performance more rapidly, which has the potential to inform center leadership and enhance quality improvement efforts.

Transplants in Foreign Countries Among Patients Removed from the US Transplant Waiting List.

Transplant tourism, where patients travel to foreign countries specifically to receive a transplant, is poorly characterized. This study examined national data to determine the minimum scope of this practice. US national waiting list removal data were analyzed. Waiting list removals for transplant without a corresponding US transplant in the database were reviewed via a data validation query to transplant centers to identify foreign transplants. Additionally, waiting list removal records with text field entries indicating a transplant abroad were identified. We identified 373 foreign transplants (173 directly noted; 200 from data validation); most (89.3%) were kidney transplants. Between 2001 and 2006, the annual number of waiting list removals for transplant abroad increased. Male sex, Asian race, resident and nonresident alien status and college education were significantly and independently associated with foreign transplant. Recipients from 34 states, plus the District of Columbia, received foreign transplants in 35 countries, led by China, the Philippines and India. Transplants in foreign countries among waitlisted candidates in the US are increasingly performed. The data reported here represent the minimum number of cases and the full extent of this practice cannot be determined using existing data. Additional reporting requirements are needed.

SRTR program-specific reports on outcomes: a guide for the new reader.

Differences in outcomes indeed exist among transplant programs and organ procurement organizations (OPO). A growing set of tools are available from the Scientific Registry of Transplant Recipients (SRTR) to measure and assess these outcomes in the different phases of the transplant process. These tools are not intended to compare two individual programs, rather to help identify programs whose practices may need further scrutiny, to be either avoided, corrected or emulated. To understand which differences in outcomes might be due to underlying differences in populations served and which might be due to differences in treatment, it is important to compare outcomes to 'risk-adjusted' expected values. Further, it is important to recognize and assess the role that random chance may play in these outcomes by considering the p-value or confidence interval of each estimate. We present the reader with a basic explanation of these tools and their interpretation in the context of reading the SRTR Program-Specific Reports. We describe the intended audience of these reports, including patients, monitoring and process improvement bodies, payers and others such as the media. Use of these statistics in a way that reflects a basic understanding of these concepts and their limitations is beneficial for all audiences.

Analytical methods and database design: implications for transplant researchers, 2005.

Understanding how transplant data are collected is crucial to understanding how the data can be used. The collection and use of Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) data continues to evolve, leading to improvements in data quality, timeliness and scope while reducing the data collection burden. Additional ascertainment of outcomes completes and validates existing data, although caveats remain for researchers. We also consider analytical issues related to cohort choice, timing of data submission, and transplant center variations in follow-up data. All of these points should be carefully considered when choosing cohorts and data sources for analysis. The second part of the article describes some of the statistical methods for outcome analysis employed by the SRTR. Issues of cohort and follow-up period selection lead into a discussion of outcome definitions, event ascertainment, censoring and covariate adjustment. We describe methods for computing unadjusted mortality rates and survival probabilities, and estimating covariate effects through regression modeling. The article concludes with a description of simulated allocation modeling, developed by the SRTR for comparing outcomes of proposed changes to national organ allocation policies.

The role of low-molecular-weight heparins in non-ST-segment elevation acute coronary syndromes.

Acute coronary syndromes are believed to be mediated by plaque rupture, initiation of the coagulation cascade, and platelet activation and aggregation. Compared to unfractionated heparin, the low molecular weight heparins possess several important theoretical advantages for the treatment of patients with acute coronary syndromes, including less non-specific binding, resistance to inactivation by platelet factor-4, more reliable anticoagulation effects, and greater factor anti-Xa activity. Four large studies have compared low-molecular-weight heparin therapy with unfractionated heparin therapy in patients with acute coronary syndromes. Two studies involving enoxaparin (Lovenox) have demonstrated that this therapy results in a lower incidence of adverse events compared to treatment with unfractionated heparin. One study of dalteparin (Fragmin) and one of nadroparin (Fraxiparin) have demonstrated comparable results between these low-molecular-weight heparins and unfractionated heparin. Several studies of modest size have demonstrated that low-molecular-weight heparins can be safely combined with platelet glycoprotein IIb/IIIa inhibitors. Ongoing and upcoming studies should add to current knowledge of the utilization of low-molecular-weight heparins.

Antithrombotic therapy in patients with acute coronary syndromes.

The potential armamentarium of agents used in the treatment of acute coronary syndromes continues to expand, including such well-tested agents as aspirin, unfractionated heparin, and earlier-generation fibrinolytic agents, and newer agents such as low-molecular-weight heparins, direct thrombin inhibitors, thienopyridines, platelet glycoprotein IIb/IIIa receptor inhibitors, and bolus-administration fibrinolytic agents. Older and newer antithrombotic agents have undergone and continue to undergo intensive clinical investigation in patients with the clinical spectrum of acute coronary syndromes, which includes unstable angina, non-Q-wave (non-ST-segment elevation) myocardial infarction, and ST-segment elevation myocardial infarction. These studies, often conducted on an international scope and involving thousands of patients, provide data allowing practitioners to optimize the care of patients with acute coronary syndromes. In this article, studies of these established and newer agents in the treatment of patients with acute coronary syndromes are reviewed critically and summarized. Recommendations regarding use of antithrombotic agents in patients with acute coronary syndromes are then given.

Impact of diabetes mellitus on percutaneous revascularization (CAVEAT-I). CAVEAT-I Investigators. Coronary Angioplasty Versus Excisional Atherectomy Trial.

We examined the relation between diabetes mellitus and outcomes in patients undergoing percutaneous coronary revascularization in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I), a randomized trial comparing treatment with either percutaneous transluminal coronary angioplasty or directional atherectomy for de novo lesions in native coronary arteries. Acute success and complication rates, 6-month angiographic restenosis rates, and 1-year clinical outcomes were compared between diabetic and nondiabetic patients undergoing each procedure. Acute success rates between diabetic (n = 191) and nondiabetic (n = 821) patients were similar for both revascularization techniques. Except for the need for dialysis, complication rates were also similar. Six months after atherectomy, diabetic patients had significantly more angiographic restenosis than nondiabetics (59.7% vs 47.4%) and significantly smaller minimum luminal diameters (1.20 vs 1.40 mm). Diabetics undergoing atherectomy required more frequent bypass surgery (12.8% vs 8.5%) and more repeat percutaneous revascularizations (36.5% vs 28.1%) than nondiabetics undergoing atherectomy. Restenosis rates, minimum luminal diameters and repeat revascularizations between diabetics and nondiabetics undergoing angioplasty were similar. The higher restenosis and repeat revascularization rates and the smaller minimum luminal diameter at follow-up in diabetic patients suggest that atherectomy may provide only modest benefit for these patients. The increased restenosis rate in diabetics undergoing atherectomy (but not angioplasty) requires further evaluation.

Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease.

BACKGROUND: In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease. METHODS AND RESULTS: Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46+/-8 to 114+/-11 micromol/L, P=.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), ascorbic acid produced marked improvement in dilation (2.0+/-0.6% to 9.7+/-2.0%), whereas placebo had no effect (1.1+/-1.5% to 1.7+/-1.5%, P=.003 for ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin. CONCLUSIONS: Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy.

Restenosis following coronary angioplasty: clinical presentations and therapeutic options.

Restenosis following angioplasty is an iatrogenic disease of increasing frequency. Restenosis may be defined in terms of either angiographic or clinical criteria. Definitions of angiographic restenosis have varied in different studies, accounting in part for the differences in reported restenosis rates. Most studies now define angiographic restenosis as either a > 50% loss of initial gain or an absolute lesion stenosis of > or = 50% at follow-up angiogram. Common clinical end points used in defining restenosis include recurrent angina, need for repeat revascularization, or myocardial infarction. Despite technical advances and multiple pharmacologic interventions, most studies have found that the incidence of angiographic restenosis remains in the range of 40%; in none of these studies, however, was complete angiographic follow-up obtained, and thus actual restenosis rates may be somewhat higher. In several studies, clinical restenosis has been found to occur in approximately 36-40% of patients. Thus, a minority of patients with angiographic restenosis have no clinical manifestations. Most patients who develop symptoms of restenosis develop these symptoms within the first 3 months after angioplasty. The presenting symptom in the majority of these patients is progressive exertional angina. Patients occasionally will present with unstable angina and only rarely with acute myocardial infarction. In patients who present with recurrent chest pain, several features have been found to be helpful in predicting whether they will have angiographic restenosis at follow-up angiography. Patients who present 1-6 months after angioplasty with typical anginal symptoms have a high likelihood of having angiographic restenosis. By contrast, patients who present more than 6 months after percutaneous transluminal coronary angioplasty with recurrent chest pain are more likely to have new, significant coronary lesions to account for their symptoms. Noninvasive testing in patients with clinical presentations suggestive of restenosis can, in general, add only modest information in predicting whether restenosis is indeed present. A negative exercise thallium test appears to have a high specificity in ruling out restenosis and may be helpful in patients who present with more atypical symptoms. Repeat angioplasty is the therapy most frequently utilized to treat restenosis, although coronary artery bypass surgery or medical therapy may be reasonable alternative therapies. Clinical success rates with repeat angioplasty are > 90%, and major complications are rare; however, restenosis will recur in a significant percentage of these patients. Some patients who develop such recurrent restenoses will ultimately benefit from a strategy of repeat angioplasties, although many will require surgical revascularization.

Acute, reversible left ventricular dysfunction in status asthmaticus.

Three cases of rapidly reversible severe myocardial depression are described in patients with status asthmaticus. Initial echocardiograms obtained within 1 day of hospital admission revealed global left ventricular hypokinesis with ejection fractions of 11 to 34%. Follow-up echocardiograms obtained only 3 to 8 days later revealed marked improvement of left ventricular function. Possible mechanisms responsible for the observed rapidly reversible myocardial depression and the clinical implications of this finding are discussed.

The benefits and risks of exercise training: the exercise prescription.

The physiologic responses to exercise are mediated by a complex interaction of central, peripheral, and neurohumoral stimuli designed to increase cardiopulmonary function. With repetitive exercise, significant cardiovascular and muscular adaptations occur that facilitate and enhance the response to exercise. Exercise is beneficial not only to younger healthy individuals, but to patients with many chronic medical conditions and to elderly individuals as well. Physical activity has a role in the reduction of major cardiac risk factors and in both the primary and secondary prevention of cardiac events. With proper evaluation and counseling, exercise can be performed safely, even among patients with cardiovascular and other chronic diseases. Given the high percentage of the U.S. population whose sedentary lifestyle predisposes them to the development of cardiovascular disease and the numerous beneficial effects of exercise, it is prudent to prescribe exercise as a means of improving individual and general public health.