Training and management of a multisite neuropsychological testing protocol for the Department of Veterans Affairs cooperative study evaluating on- and off-pump coronary artery bypass graft procedures.

Research study coordinators from 17 sites participating in a cardiac surgery study were trained to administer and score a brief neuropsychological test battery. Results were sent to the study's centralized laboratory for review and feedback. The average examiner errors on the first six protocols were compared with the average errors on the last six protocols over 12 months for each site. Overall, errors for the first six protocols were 4.42, and errors for the last six protocols were 1.83, representing a significant overall decline. Errors for instruction, administration, and recording showed a significant decrease over time. Despite ongoing feedback to examiners, scoring errors did not decline significantly overall; this suggests that a review of all protocols is necessary to achieve reliable scoring. However, when examiners' number of protocols completed was compared with number of scoring errors per protocol, there was a trend for examiners who had completed more protocols to show more improvement in scoring.

Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity.

BACKGROUND: The purpose of this study was to determine whether coronary artery bypass grafting without cardiopulmonary bypass (off-pump CABG) decreases risk-adjusted operative death and major complications after coronary artery bypass grafting in selected patients. METHODS: Using The Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database, procedural outcomes were compared for conventional and off-pump CABG procedures from January 1, 1998, through December 31, 1999. Mortality and major complications were examined, both as unadjusted rates and after adjusting for known base line patient risk factors. RESULTS: A total of 126 experienced centers performed 118,140 total CABG procedures. The number of off-pump CABG cases was 11,717 cases (9.9% of total cases). The use of an off-pump procedure was associated with a decrease in risk-adjusted operative mortality from 2.9% with conventional CABG to 2.3% in the off-pump group (p < 0.001). The use of an off-pump procedure decreased the risk-adjusted major complication rate from 14.15% with conventional CABG to 10.62% in the off-pump group (p < 0.0001). Patients receiving off-pump procedures were less likely to die (adjusted odds ratio 0.81, 95% CI 0.70 to 0.91) and less likely to have major complications (adjusted odds ratio 0.77, 95% CI 0.72 to 0.82). CONCLUSIONS: Off-pump CABG is associated with decreased mortality and morbidity after coronary artery bypass grafting. Off-pump CABG may prove superior to conventional CABG in appropriately selected patients.

A decade's experience with quality improvement in cardiac surgery using the Veterans Affairs and Society of Thoracic Surgeons national databases.

OBJECTIVE: To review the Department of Veteran Affairs (VA) and the Society of Thoracic Surgeons (STS) national databases over the past 10 years to evaluate their relative similarities and differences, to appraise their use as quality improvement tools, and to assess their potential to facilitate improvements in quality of cardiac surgical care. SUMMARY BACKGROUND DATA: The VA developed a mandatory risk-adjusted database in 1987 to monitor outcomes of cardiac surgery at all VA medical centers. In 1989 the STS developed a voluntary risk-adjusted database to help members assess quality and outcomes in their individual programs and to facilitate improvements in quality of care. METHODS: A short data form on every veteran operated on at each VA medical center is completed and transmitted electronically for analysis of unadjusted and risk-adjusted death and complications, as well as length of stay. Masked, confidential semiannual reports are then distributed to each program's clinical team and the associated administrator. These reports are also reviewed by a national quality oversight committee. Thus, VA data are used both locally for quality improvement and at the national level with quality surveillance. The STS dataset (217 core fields and 255 extended fields) is transmitted for each patient semiannually to the Duke Clinical Research Institute (DCRI) for warehousing, analysis, and distribution. Site-specific reports are produced with regional and national aggregate comparisons for unadjusted and adjusted surgical deaths and complications, as well as length of stay for coronary artery bypass grafting (CABG), valvular procedures, and valvular/CABG procedures. Both databases use the logistic regression modeling approach. Data for key processes of care are also captured in both databases. Research projects are frequently carried out using each database. RESULTS: More than 74,000 and 1.6 million cardiac surgical patients have been entered into the VA and STS databases, respectively. Risk factors that predict surgical death for CABG are very similar in the two databases, as are the odds ratios for most of the risk factors. One major difference is that the VA is 99% male, the STS 71% male. Both databases have shown a significant reduction in the risk-adjusted surgical death rate during the past decade despite the fact that patients have presented with an increased risk factor profile. The ratio of observed to expected deaths decreased from 1.05 to 0.9 for the VA and from 1.5 to 0.9 for the STS. CONCLUSION: It appears that the routine feedback of risk-adjusted data on local performance provided by these programs heightens awareness and leads to self-examination and self-assessment, which in turn improves quality and outcomes. This general quality improvement template should be considered for application in other settings beyond cardiac surgery.

Off-pump coronary artery bypass is associated with improved risk-adjusted outcomes.

BACKGROUND: The impact of off-pump median sternotomy coronary artery bypass grafting procedures on risk-adjusted mortality and morbidity was evaluated versus on-pump procedures. METHODS: Using the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Program records from October 1997 through March 1999, nine centers were designated as having experience (with at least 8% coronary artery bypass grafting procedures performed off-pump). Using all other 34 Veterans Affairs cardiac surgery programs, baseline logistic regression models were built to predict risk of 30-day operative mortality and morbidity. These models were then used to predict outcomes for patients at the nine study centers. A final model evaluated the impact of the off-pump approach within these nine centers adjusting for preoperative risk. RESULTS: Patients treated off-pump (n = 680) versus on-pump (n = 1,733) had lower complication rates (8.8% versus 14.0%) and lower mortality (2.7% versus 4.0%). Risk-adjusted morbidity and mortality were also improved for these patients (0.52 and 0.56 multivariable odds ratios for off-pump versus on-pump, respectively, p < 0.05). CONCLUSIONS: An off-pump approach for coronary artery bypass grafting procedures is associated with lower risk-adjusted morbidity and mortality.

Localization of telomerase hTERT protein and survivin in placenta: relation to placental development and hydatidiform mole.

OBJECTIVE: To find if a difference in telomerase or survivin expression exists between non-neoplastic tissues and hydatidiform moles, and explore expression of those proteins in normal placental development, post-term gestation, and preeclampsia. METHODS: Formalin-fixed placental tissues were selected from collections of the Department of Pathology at the University of Colorado. Five specimens of each trimester, five each of preeclamptic and post-term placentas, and 23 molar pregnancies were selected. The telomerase catalytic protein hTERT was localized in placental tissues using the catalyzed signal amplification system, and survivin was localized by conventional immunoperoxidase method. Staining was graded on a scale of zero to 4. RESULTS: hTERT staining was detected in sections of 42 of 48 specimens (23 of 23 hydatidiform moles, 19 of 25 non-neoplastic placental tissues). The intensity of staining for hTERT was higher in hydatidiform moles (mean 3.3, median 3) compared with levels in non-neoplastic placental tissues (mean 0.92, median 1) (P <.001). Survivin was detected in 39 of 48 specimens (22 of 23 hydatidiform moles, 17 of 25 non-neoplastic placental tissues). Compared with non-neoplastic tissues (mean 0.88, median 1), survivin levels were elevated in hydatidiform moles (mean 1.35, median 1) (P =.031). CONCLUSION: Survivin and telomerase were increased in hydatidiform moles, suggesting that regulation of apoptosis and stabilization of telomere length might be involved in neoplastic transformation of the placenta. The patterns of expression observed for survivin and telomerase in non-neoplastic placental tissues suggest that the control of apoptosis and stabilization of telomeric DNA might also be involved in normal gestational development.

Effects of race, with or without gender, on operative mortality after coronary artery bypass grafting: a study using The Society of Thoracic Surgeons National Database.

BACKGROUND: Although gender is known to be an independent predictor of 30-day operative mortality (OM) after coronary artery bypass grafting, the purpose of this study was to determine whether race-alone or in combination with gender-affects OM. METHODS: For 1994 to 1996, The Society of Thoracic Surgeons database records for 441,542 coronary artery bypass grafting-only procedures were analyzed. Baseline annual multivariate models were built. Gender and race were added to each model. Risk-adjusted OM rates were then calculated for race, gender, and their combination. Patients were also stratified into groups of comparable predicted OM to allow for a direct comparison of risk-matched Caucasians and non-Caucasians. RESULTS: Of the procedures, 28.2% were on women and 8.5% on non-Caucasians. Overall, OM was 3.29%. Multivariate risk-adjusted OM varied by gender and race (p < 0.10). Risk-adjusted OM rates (with 95% confidence intervals) were 4.0% (3.9% to 4.1%) for females and 3.2% (3.2% to 3.3%) for males. Risk-adjusted OM rates were 3.9% (3.7% to 4.1%) for non-Caucasians and 3.3% (3.2% to 3.3%) for Caucasians. Among equally risk-matched Caucasians and non-Caucasians, non-Caucasians had significantly higher (p < 0.005) mortality among the lower risk subgroups (up to 10% predicted OM) but not among the higher risk subgroups. CONCLUSIONS: Race and gender are independent predictors of adverse outcome following coronary artery bypass grafting, holding all other risk factors constant.

Changes in health-related quality of life following coronary artery bypass graft surgery.

BACKGROUND: There are limited data to help clinicians identify patients likely to have an improvement in quality of life following CABG surgery. We evaluated the relationship between preoperative health status and changes in quality of life following CABG surgery. METHODS: We evaluated 1,744 patients enrolled in the VA Cooperative Processes, Structures, and Outcomes in Cardiac Surgery study who completed preoperative and 6-month postoperative Short Form-36 (SF-36) surveys. The primary outcome was change in the Mental Component Summary (MCS) and Physical Component Summary (PCS) scores from the SF-36. RESULTS: On average, physical and mental health status improved following the operation. Preoperative health status was the major determinant of change in quality of life following surgery, independent of anginal burden and other clinical characteristics. Patients with MCS scores less than 44 or PCS scores less than 38 were most likely to have an improvement in quality of life. Patients with higher preoperative scores were unlikely to have an improvement in quality of life. CONCLUSIONS: Patients with preoperative health status deficits are likely to have an improvement in their quality of life following CABG surgery. Alternatively, patients with relatively good preoperative health status are unlikely to have a quality of life benefit from surgery and the operation should primarily be performed to improve survival.

Risk factors for intermediate-term survival after coronary artery bypass grafting.

BACKGROUND: Risk factors for short-term mortality after coronary artery bypass grafting are well established, but little is known about risk factors for intermediate-term mortality. METHODS: We analyzed the outcomes of 11,815 patients undergoing coronary artery bypass grafting in one of the 43 cardiac surgery programs of the Department of Veteran Affairs. Risk factors for intermediate- and short-term mortality were determined using Cox proportional hazards regression models. Effects of risk factors during these two periods were explicitly compared. RESULTS: We found important differences in mortality risk-factor sets between the intermediate- and short-term periods after coronary artery bypass grafting. The majority of predictors of intermediate-term mortality were noncardiac-related variables, whereas the majority of predictors of short-term mortality were cardiac-related variables. Impaired functional status, chronic obstructive pulmonary disease, and renal dysfunction had greater effects in the intermediate-term period. Previous heart operation, angina class III or IV, previous myocardial infarction, and preoperative use of an intraaortic balloon pump had greater effects in the short-term period. CONCLUSIONS: The risk factors for intermediate-term mortality identified in this study can augment preoperative risk assessment and counseling of patients. Clinicians should be aware of the importance of noncardiac-related variables as predictors of mortality in the intermediate-term period after coronary artery bypass grafting.

Identification of risk factors for increased cost, charges, and length of stay for cardiac patients.

BACKGROUND: In this study we explored different risk model options to provide clinicians with predictions for resource utilization. The hypotheses were that predictors of mortality are not predictive of resource consumption, and that there is a correlation between cost estimates derived using a cost-to-charge ratio or a product-line costing approach. METHODS: From March 1992 to June 1995, 2,481 University of Colorado Hospital patients admitted for ischemic heart disease were classified by diagnosis-related group code as having undergone or experienced coronary bypass procedures (CBP), percutaneous cardiovascular procedures (PCVP), acute myocardial infarction (AMI), and other cardiac-related discharges (Other). For each diagnosis-related group, Cox proportional hazards models were developed to determine predictors of cost, charges, and length of stay. RESULTS: The diagnosis groups differed in the clinical factors that predicted resource use. As the two costing methods were highly correlated, either approach may be used to assess relative resource consumption provided costs are reconciled to audited financial statements. CONCLUSIONS: To develop valid prediction models for costs of care, the clinical risk factors that are traditionally used to predict risk-adjusted mortality may need to be expanded.

Quantitative telomerase expression in glioblastomas shows regional variation and down-regulation with therapy but no correlation with patient outcome.

Despite the nearly ubiquitous expression of telomerase in almost all types of malignant human tumors, studies have shown widely varying positivity in the highest-grade glioma, the glioblastomas (GBMs), ranging from 26% to 100% of tumors analyzed. We have previously shown significant variability in positive versus negative telomerase expression from region to region within the same GBM. In this study, we hypothesized that application of new quantitative methodology would extend our previous observations and identify whether there is heterogeneity in levels of protein expression even within areas positive for telomerase in high-grade gliomas. Finally, we sought to correlate quantitative telomerase expression with patient outcome and therapeutic response. Quantitative analysis was achieved by polymerase chain-based TRAP assay with phosphorimager analysis and compared with clinical information obtained from 19 patients, most with primary, untreated GBMs. Results showed up to 3-fold variability in telomerase levels across multiple regional samples from the same patient, as well as between patients. In 5 of 6 patients with recurrent tumors who had received intervening radiation therapy or chemotherapy, telomerase was downregulated in the second, post-therapy sample. These data provide in vivo corroboration of recent in vitro experiments showing telomerase downregulation after radiation therapy or chemotherapy treatment of cell lines. Our finding of variability in levels of telomerase expression in GBMs parallels the known heterogeneity of these tumors for histologic features and cell growth-related factors. Statistical analysis showed no relationship between TRAP score and either time to clinical progression or time to death.

Mild renal failure is associated with adverse outcome after cardiac valve surgery.

The present study was performed to ascertain whether the presence of mild renal failure (defined as a serum creatinine concentration of 1. 5 to 3.0 mg/dL) is an independent risk factor for adverse outcome after cardiac valve surgery. An extensive set of preoperative and postoperative data was collected in 834 prospectively evaluated patients undergoing cardiac valve surgery at 14 Veterans Affairs Medical Centers. Univariate and multivariable analyses were performed to determine whether an independent association of mild renal dysfunction with adverse outcomes was present. Patients with mild renal failure had significantly greater 30-day mortality rates (P = 0.001; 16% versus 6%) and frequency of postoperative bleeding (P = 0.023; 16% versus 8%), respiratory complications (P = 0.02, 29% versus 16%), and cardiac complications (P = 0.002; 18% versus 7%) than patients with normal renal function (serum creatinine <1.5 mg/dL) when controlling for multiple other variables. The presence of a serum creatinine concentration of 1.5 to 3.0 mg/dL is significantly and independently associated with adverse outcomes after cardiac valve surgery.

MRI findings in haemophilic joints treated with radiosynoviorthesis with development of an MRI scale of joint damage.

We hypothesized that magnetic resonance imaging (MRI) scans taken prior to radiosynoviorthesis may be predictive of response to the procedure in persons with haemophilia. Specifically, response would be inversely related to the severity of synovial hyperplasia. Radiosynoviorthesis was administered to 21 joints with recurrent haemorrhage (target joints). A detailed self-report of haemorrhage history, joint evaluation with scoring according to the World Federation of Haemophilia orthopaedic joint and pain scales, plain radiographs, and MRI studies of the joints were performed pre- and post-radiosynoviorthesis. To augment comparison of the MRI findings to those assessed using the Arnold-Hilgartner and Pettersson scales, a provisional MRI scale for evaluation of haemophilic arthropathy was designed. We found the MRI findings prior to the procedure were not predictive of clinical response; independent of the severity of synovial hyperplasia, most joints bled less and showed improvement by the WFH orthopaedic score. There was generally no change in the severity of synovial hyperplasia after the procedure. We conclude that MRI evaluation is not routinely indicated prior to radiosynoviorthesis.

The STS National Database: current changes and challenges for the new millennium. Committee to Establish a National Database in Cardiothoracic Surgery, The Society of Thoracic Surgeons.

BACKGROUND: The Society of Thoracic Surgeons (STS) established the National Database (NDB) for Cardiac Surgery in 1989. Since then it has grown to be the largest database of its kind in medicine. The NDB has been one of the pioneers in the analysis and reporting of risk-adjusted outcomes in cardiothoracic surgery. METHODS AND RESULTS: This report explains the numerous changes in the NDB and its structure that have occurred over the past 2 years. It highlights the benefits of these changes, both to the individual member participants and to the STS overall. Additionally, the vision changes to the NDB and reporting structure are identified. The individuals who have participated in this effort since 1989 are acknowledged, and the STS owes an enormous debt of gratitude to each of them. CONCLUSIONS: Because of their collective efforts, the goal to establish the STS NDB as a "gold standard" worldwide for process and outcomes analysis related to cardiothoracic surgery is becoming a reality.

Clinical science research.

Clinical science research incorporates the fields of clinical investigation and health services research. With a focus on the use of either human specimens or subjects, clinical investigation research projects translate knowledge gained from basic science research based on animal models for disease. The goal of clinical investigation is to develop new prevention, intervention, and therapeutic approaches to improve patient clinical outcomes. In contrast, health services research focuses on the improvement of the efficacy, cost-effectiveness, and outcomes of care. Health services research projects examine options to improve the health care delivery system, organization, financing, and reimbursement mechanisms in place today. The purpose of this article is to review common terminology and methodologic approaches that are used in clinical science research. The process of designing a research project is reviewed. Beginning with the development of a research question and hypothesis, the steps for successful completion of the project are discussed. Different study design approaches are presented with their respective strengths and weaknesses. The challenges associated with conducting a clinical research study are discussed, including the development of an appropriate sampling strategy, the designing of data collection, instruments, and the assurance of study data integrity. Possible threats to study validity and generalizability are assessed.One the major advantages of clinical research is that it offers an opportunity to study clinical questions in the clinical setting without the expenses of a basic research laboratory and basic science technology. Thus important clinical questions related to patient care, new technology assessment, clinical practice management, health care administration, or health policy may be addressed.

Association of fast-track cardiac management and low-dose to moderate-dose glucocorticoid administration with perioperative hyperglycemia.

OBJECTIVE: To delineate associations between preoperative risk factors and clinical processes of care and perioperative glucose tolerance in patients managed on a fast-track cardiac surgery clinical pathway with prebypass methylprednisolone administration. DESIGN: Retrospective sequential cohort study. SETTING: University-affiliated Department of Veterans Affairs medical center. PARTICIPANTS: Fast-track patients (n = 293; n = 72 low-dose methylprednisolone [100-125 mg]; n = 221 moderate-dose methylprednisolone [500 mg]) plus pre-fast-track patients (n = 258; no methylprednisolone) undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariate linear regression was used to model the association of 17 preoperative risk and intraoperative process-of-care variables with serum glucose concentration on arrival in the intensive care unit. Preoperative serum glucose concentrations were not significantly different among the pre-fast-track, fast-track with low-dose methylprednisolone, and fast-track with moderate-dose methylprednisolone cohorts (129 +/- 54, 137 +/- 55, 127 +/- 46 mg/dL [mean +/- SD]). Postoperative serum glucose concentrations were significantly different (171 +/- 58, 223 +/- 56, 250 +/- 75 mg/dL; p < 0.03, for all pairwise comparisons). Using backward elimination from the full 17-variable multivariate model (R-square = 0.63), 4 variables remained significant (all p < 0.0001; R-square = 0.60): (1) Preoperative diabetes status (adjusted mean post-operative glucose level, mg/dL; [95% confidence interval (CI)]): no treatment, 193 (188-199); oral agent, 276 (262-291); insulin requiring, 301 (283-320); (2) steroid group: pre-fast-track, 201 (195-209), fast-track with low-dose methylprednisolone, 271 (256-287); fast-track with moderate-dose methylprednisolone, 295 (284-306); (3) volume of glucose-containing cardioplegia (beta coefficient, 95% CI): 2.22% (1.37-3.10) increase per 100 mL; and (4) intraoperative epinephrine infusion: none, 231 (224-239); yes, 276 (264-288). No significant interactions were identified. No significant effect of opioid dose was observed. CONCLUSION: At this institution, implementation of the fast-track pathway was associated with a deterioration of glucose tolerance. Preoperative diabetes, pre-cardiopulmonary bypass administration of steroids, volume of glucose-containing cardioplegia solution administered, and use of epinephrine infusions were significantly associated multivariate factors.

Telomerase is a highly sensitive and specific molecular marker in fine-needle aspirates of breast lesions.

PURPOSE: Telomerase has been detected in a majority of human malignant tumors, making telomerase activity (TA) one key difference between mortal and immortal cells. In this study, we evaluated in blind-trial fashion the association of TA with cytologic and final clinical/pathologic diagnosis in fine-needle aspirates (FNAs) of breast lesions. MATERIALS AND METHODS: In 172 FNAs, including 80 samples that were cytologically malignant, 18 that were atypical but not diagnostic for malignancy, and 74 that were cytologically benign, TA was determined by a modified nonradioactive telomeric repeat amplification protocol (TRAP) assay. Final diagnosis was made by pathologic examination of follow-up surgical material available for all the cytologically malignant samples, a majority of the cytologically atypical samples, and a portion of the cytologically benign samples. RESULTS: TA was detected in 85 of 172 samples. Comparison of the cytologic and histologic diagnoses with TA showed that 80 of 87 samples from patients with breast cancer were telomerase-positive, resulting in a sensitivity of 92%. TA was found in four of five FNAs from carcinomas that were considered cytologically atypical but not diagnostic for malignancy. Eighty of 85 samples from patients with benign breast lesions were telomerase-negative, revealing a specificity of 94%. The five positive cases in this group were all fibroadenomas with low TA. Among the 18 cases with a cytologic diagnosis of atypia, there was a strong positive relationship between TRAP findings and histologic diagnosis. CONCLUSION: The detection of TA in FNAs of breast lesions is a highly sensitive and specific marker of malignancy and may be used as an adjunct in cases with an equivocal cytologic diagnosis.

Stroke in cardiac surgical patients: determinants and outcome.

BACKGROUND: Despite improving outcomes in cardiac surgical patients, stroke continues to remain a major complication. Few prospective studies are available on postoperative stroke. The present study was conducted to elucidate the incidence and predictors of stroke in a large group of cardiac surgical patients. METHODS AND RESULTS: Prospective data collected on 4,941 patients undergoing cardiac surgery were subjected to univariate and logistic regression analyses (98.4% men; 72% older than 60 years; 9.1% with history of prior stroke; 80.4% underwent isolated coronary artery bypass grafting). Stroke predictors include history of stroke and hypertension, older age, systolic hypertension, bronchodilator and diuretic use, high serum creatinine, surgical priority, great vessel repair, use of inotropic agents after cardiopulmonary bypass, and total cardiopulmonary bypass time (p < 0.05 for all comparisons). Median intensive care unit and hospital stays were longer, and hospital mortality and 6-month mortality were higher for patients with stroke (p < 0.001). CONCLUSIONS: Stroke after cardiac surgical procedures is a morbid event. Identification of predictors and development of strategies to modify these factors should lead to a lower incidence of stroke.

The 1996 coronary artery bypass risk model: the Society of Thoracic Surgeons Adult Cardiac National Database.

BACKGROUND: The Society of Thoracic Surgeons Adult Cardiac National Database has recently completed the update for the 1996 risk model to be used to estimate the risk of operative death for isolated coronary artery bypass graft (CABG) procedures. METHODS: We placed emphasis on clinical relevance, data quality, data completeness, and univariate analyses. A logistic regression approach was used to develop the 1996 CABG-only risk model. RESULTS: Odds ratios for the factors with highest risk are multiple reoperations (OR = 4.3), emergent salvage status (OR = 3.7), and first reoperation (OR = 2.7). Standard performance measures indicated the model had high predictive power and an acceptable level of calibration after adjustment for a large sample size effect. CONCLUSION: The most current STS risk model of CABG operative mortality is a reliable and statistically valid tool. The 1996 CABG-only model has been approved for use by The Society of Thoracic Surgeons.