Overall conceptual framework for studying the genetics of autoimmune diseases following vaccination: a regulatory perspective.

The US Vaccine Adverse Event Reporting System contains case reports of autoimmune diseases (ADs) occurring following vaccinations. ADs are rare and occur in unvaccinated people, making the potential association between vaccines and ADs challenging to evaluate. Developing mechanistic pathways that link genes, immune mediators, vaccine components and ADs would be helpful for hypothesis generation, enhancing theories of biologic plausibility and grouping rare autoimmune adverse events to increase the ability to detect and evaluate safety signals. Here, we propose a conceptual framework for investigating the genetics of ADs as safety signals following vaccination, potentially contributing to the identification of relevant biomarkers. We also discuss a study design that incorporates genetic information into postmarket clinical evaluation of autoimmune adverse events following vaccination.

Implementation of clinical practice guidelines for prevention of thromboembolism in spinal cord injury.

BACKGROUND/OBJECTIVES: The purpose of this study was to determine whether publication of the "Prevention of Thromboembolism in Spinal Cord Injury" clinical practice guideline (CPG) changed patient management and whether adherence to CPG recommendations improved after a targeted implementation strategy. METHODS: Data were abstracted from medical records of 134 and 520 patients with acute and chronic spinal cord injury (SCI), respectively, from 6 Veterans Affairs medical centers over 3 time periods: prepublication (T1), preimplementation (T2), and postimplementation (T3) of the CPG. Targeted interventions were developed to address provider-perceived barriers to guideline adherence, based on findings from focus groups conducted at each site. The interventions incorporated two implementation strategies: standardized documentation templates/standing orders and social marketing/outreach visits. RESULTS: Use of the specified duration for pharmacologic prophylaxis increased from 60% to 65% to 75% of patients with acute SCI in T1, T2, and T3, respectively (P = 0.060 and 0.041 for T1 vs T2 and T2 vs T3, respectively). Rates of use for individual pharmacologic prophylaxis agents changed significantly over the course of the study, with use of low-molecular-weight heparin increasing from 7% in T1 to 42% in T3. Physical assessments for thrombosis on hospitalization days 1 and 30 improved between T2 and T3. Use of prophylaxis in chronically injured patients with new risk factors for thromboembolism increased from 16% to 31% to 34% during T1, T2, and T3 (P = 0.001 and 0.87, respectively). CONCLUSIONS: The CPG publication had only a modest effect on practice. Use of structured implementation further increased the adherence to some CPG recommendations for thromboembolism prophylaxis. Similar implementation strategies should be considered for CPG recommendations with low adherence and high potential for morbidity and mortality.

Provider adherence to implementation of clinical practice guidelines for neurogenic bowel in adults with spinal cord injury.

BACKGROUND/OBJECTIVES: Clinical Practice Guidelines (CPGs) have been published on a number of topics in spinal cord injury (SCI) medicine. Research in the general medical literature shows that the distribution of CPGs has a minimal effect on physician practice without targeted implementation strategies. The purpose of this study was to determine (a) whether dissemination of an SCI CPG improved the likelihood that patients would receive CPG recommended care and (b) whether adherence to CPG recommendations could be improved through a targeted implementation strategy. Specifically, this study addressed the "Neurogenic Bowel Management in Adults with Spinal Cord Injury" Clinical Practice Guideline published in March 1998 by the Consortium for Spinal Cord Medicine METHODS: CPG adherence was determined from medical record review at 6 Veterans Affairs SCI centers for 3 time periods: before guideline publication (T1), after guideline publication but before CPG implementation (T2), and after targeted CPG implementation (T3). Specific implementation strategies to enhance guideline adherence were chosen to address the barriers identified by SCI providers in focus groups before the intervention. RESULTS: Overall adherence to recommendations related to neurogenic bowel did not change between T1 and T2 (P = not significant) but increased significantly between T2 and T3 (P < 0.001) for 3 of 6 guideline recommendations. For the other 3 guideline recommendations, adherence rates were noted to be high at T1. CONCLUSIONS: While publication of the CPG alone did not alter rates of provider adherence, the use of a targeted implementation plan resulted in increases in adherence rates with some (3 of 6) CPG recommendations for neurogenic bowel management.

Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study.

OBJECTIVES: This study defined long-term patency of saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts. BACKGROUND: This VA Cooperative Studies Trial defined 10-year SVG patency in 1,074 patients and left IMA patency in 457 patients undergoing coronary artery bypass grafting (CABG). METHODS: Patients underwent cardiac catheterizations at 1 week and 1, 3, 6, and 10 years after CABG. RESULTS: Patency at 10 years was 61% for SVGs compared with 85% for IMA grafts (p < 0.001). If a SVG or IMA graft was patent at 1 week, that graft had a 68% and 88% chance, respectively, of being patent at 10 years. The SVG patency to the left anterior descending artery (LAD) (69%) was better (p < 0.001) than to the right coronary artery (56%), or circumflex (58%). Recipient vessel size was a significant predictor of graft patency, in vessels >2.0 mm in diameter SVG patency was 88% versus 55% in vessels 2.0 mm in diameter.

Transthoracic versus transhiatal esophagectomy: a prospective study of 945 patients.

OBJECTIVE: Debate continues as to whether transhiatal esophagectomy results in lower morbidity and mortality than transthoracic esophagectomy. Most data addressing this issue are derived from single-institution studies. To investigate this question from a nationwide multicenter perspective, we used the Veterans Administration National Surgical Quality Improvement Program to prospectively analyze risk factors for morbidity and mortality in patients undergoing transthoracic esophagectomy or transhiatal esophagectomy from 1991 to 2000. METHODS: Univariate and multivariate analyses were performed on 945 patients (mean age, 63 +/- 10 years). There were 562 transthoracic esophagectomies and 383 transhiatal esophagectomies in 105 hospitals, with complete 30-day outcomes recorded. RESULTS: There were no differences in recorded preoperative variables between the groups that might bias any comparisons. Overall mortality was 10.0% (56/562) for transthoracic esophagectomy and 9.9% (38/383) for transhiatal esophagectomy (P =.983). Morbidity occurred in 47% (266/562) of patients after transthoracic esophagectomy and in 49% (188/383) of patients after transhiatal esophagectomy (P =.596). Risk factors for mortality common to both groups included a serum albumin value of less than 3.5 g/dL, age greater than 65 years, and blood transfusion of greater than 4 units (P <.05). When comparing transthoracic esophagectomy with transhiatal esophagectomy, there was no difference in the incidence of respiratory failure, renal failure, bleeding, infection, sepsis, anastomotic complications, or mediastinitis. Wound dehiscence occurred in 5% (18/383) of patients undergoing transhiatal esophagectomy and only 2% (12/562) of patients undergoing transthoracic esophagectomy (P =.036). CONCLUSIONS: These data demonstrate no significant differences in preoperative variables and postoperative mortality or morbidity between transthoracic esophagectomy and transhiatal esophagectomy on the basis of a 10-year, prospective, multi-institutional, nationwide study.

Outcomes after esophagectomy: a ten-year prospective cohort.

BACKGROUND: The Department of Veterans Affairs National Surgical Quality Improvement Program is a unique resource to prospectively analyze surgical outcomes from a cross-section of surgical services nationally. We used this database to assess risk factors for morbidity and mortality after esophagectomy in Veterans Affairs Medical Centers from 1991 to 2001. METHODS: A total of 1,777 patients underwent an esophagectomy at 109 Veterans Affairs hospitals with complete in-hospital and 30-day outcomes recorded. Bivariate and multivariable analyses were completed. RESULTS: Thirty-day mortality was 9.8% (174/1,777) and the incidence of one or more of 20 predefined complications was 49.5% (880/1,777). The most frequent postoperative complications were pneumonia in 21% (380/1,777), respiratory failure in 16% (288/1,777), and ventilator support more than 48 hours in 22% (387/1,777). Preoperative predictors of mortality based on multivariable analysis included neoadjuvant therapy, blood urea nitrogen level of more than 40 mg/dL, alkaline phosphatase level of more than 125 U/L, diabetes mellitus, alcohol abuse, decreased functional status, ascites, and increasing age. Preoperative factors impacting morbidity were increasing age, dyspnea, diabetes mellitus, chronic obstructive pulmonary disease, alkaline phosphatase level of more than 125 U/L, lower serum albumin concentration, increased complexity score, and decreased functional status. Intraoperative risk factors for mortality included the need for transfusion; intraoperative risk factors for morbidity included the need for transfusion and longer operative time. CONCLUSIONS: These data constitute the largest prospective outcomes cohort in the literature and document a near 50% morbidity rate and 10% mortality rate after esophagectomy. Data from this study can be used to better stratify patients before esophagectomy.

Association between initial empirical therapy and decreased length of stay among veteran patients hospitalized with community acquired pneumonia.

This investigation assessed the impact of initial empirical antimicrobial therapy on the outcome of therapy for community acquired pneumonia (CAP) patients and on patients' length of stay (LOS) in the hospital. Hospital records for 165 patients with pneumonia admitted to the Edward Hines, Jr. VA Hospital between 1 October 1997, and 31 March 2000, were reviewed. Criteria for CAP were met for 92 of 165 patients. Comparisons were made between patients treated with azithromycin and with other parenteral antibiotics (the reference group). No statistical differences were observed between the treatment groups for the risk factors. The azithromycin group patients were slightly older with a mean age of 69 years versus 66 years (P=0.23). Patients treated with parenteral azithromycin had on average, a shorter length of hospitalization namely 4.6 days compared with 9.7 days for patients treated with the other antibiotics (log-rank test, P=0.0001). In order to make the two groups of patients more alike we considered patients' data set without intensive care unit (ICU) admissions. The conclusion was the same namely azithromycin monotherapy was associated with a decreased duration of hospital stay.