Kenneth E. James

Warfarin in the Prevention of Stroke Associated with Nonrheumatic Atrial Fibrillation

BACKGROUND Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. METHODS We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. RESULTS Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history. CONCLUSIONS Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

Silent Cerebral Infarction in Patients With Nonrheumatic Atrial Fibrillation

BACKGROUND Cerebral infarction in patients with atrial fibrillation may vary from being clinically silent to catastrophic. The prevalence of silent cerebral infarction and its effect as a risk factor for symptomatic stroke are important considerations for the evaluation of patients with atrial fibrillation. METHODS AND RESULTS This Veterans Affairs cooperative study was a double-blind controlled trial designed primarily to determine the efficacy of warfarin for the prevention of stroke in neurologically normal patients with nonrheumatic atrial fibrillation. It also was designed to evaluate patients with silent cerebral infarction. Computed tomography scans of the head were performed at entry, at the time of any subsequent stroke, and at termination of follow-up on all patients who completed the study without a neurological event. Of 516 evaluable scans performed at entry, 76 (14.7%) had evidence of one or more silent cerebral infarcts. Age (P = .011), a history of hypertension (P = .003), active angina (P = .012), and elevated mean systolic blood pressure (P < .001) were associated with the presence of this finding. Silent cerebral infarction occurred during the study at rates of 1.01% and 1.57% per year for the placebo and warfarin treatment groups, respectively (NS). Silent cerebral infarction at entry was not an independent predictor of later symptomatic stroke, but active angina was a significant predictor; 15% of the placebo-assigned patients with angina developed a stroke compared with 5% of the placebo-assigned patients without angina. CONCLUSIONS Silent cerebral infarction is frequently seen in asymptomatic patients with atrial fibrillation. Age, history of hypertension, active angina, and elevated mean systolic blood pressure were associated with silent infarction at entry. The sample size was too small to determine whether warfarin had an effect on the incidence of silent infarction during the trial. Active angina at baseline was the only significant independent predictor for the later development of symptomatic stroke.

Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia.

BACKGROUND: A previously published clinical trial of epidural-supplemented versus general anesthesia, Veterans Affairs Cooperative Study No. 345, showed no difference in 30-day mortality and morbidity rates between the two treatments. We hypothesized that long-term postoperative survival would be increased by epidural anesthesia/analgesia supplementation during colon cancer resection. METHODS: We studied long-term survival after resection of colon cancer in a trial of general anesthesia with and without epidural anesthesia and analgesia supplementation for resection of colon cancer in Veterans Affairs Cooperative Study No. 345. Cox and log-normal survival models were used to test the effects of pathological stage, type of anesthesia and other covariates on survival in 177 patients. RESULTS: The presence of distant metastases had the greatest effect on survival. Thus, analyses were performed separately for patients with and without metastases. For those without metastasis, the hazard ratio for the treatment effects changed at 1.46 years. Before 1.46 years, epidural supplementation was associated with improved survival (P = 0.012), while later, the type of anesthesia did not appear to affect survival (P = 0.27). Hypertension was associated with poorer survival (P = 0.029), as was alcoholism in patients who received epidural anesthesia (P = 0.014). Survival of patients with metastases was unaffected by type of anesthesia. There was a significant age by hypertension interaction (P = 0.002). Patients survived longer if they were hypertensive, but had reduced survival if they were older than 66 years and hypertensive. CONCLUSION: Epidural supplementation was associated with enhanced survival among patients without metastases before 1.46 years. Epidural anesthesia had no effect on survival of patients with metastases. Additional studies to confirm or refute these findings are warranted.

Determinants of outcomes of sinus surgery: A multi-institutional prospective cohort study

OBJECTIVES: 1) To measure the proportion of patients with chronic rhinosinusitis (CRS) who experience clinically significant improvement after endoscopic sinus surgery (ESS) in a prospective, multi-institutional fashion. 2) To identify preoperative characteristics that predict clinically significant improvement in quality of life (QOL) after ESS. STUDY DESIGN: Prospective, multi-institutional cohort study. SETTING: Academic tertiary care centers. SUBJECTS AND METHODS: A total of 302 patients with CRS from three centers were enrolled between July 2004 and December 2008 and followed for an average of 17.4 months postoperatively. Preoperative patient characteristics, CT scan, endoscopy score, and pre- and postoperative quality of life (QOL) data were collected. Univariate and multivariate analyses were performed. RESULTS: Patients improved an average of 15.8 percent (18.9 points) on the Rhinosinusitis Disability Index and 21.2 percent (21.2 points) on the Chronic Sinusitis Survey (both P < 0.001). Patients significantly improved on all eight Medical Outcomes Study Short Form-36 (SF-36) subscales (all P < 0.001). Among patients with poor baseline QOL, 71.7 percent of patients experienced clinically significant improvement on the RSDI and 76.1 percent on the CSS. Patients undergoing primary surgery were 2.1 times more likely to improve on the RSDI (95% confidence interval [CI], 1.2, 3.4; P = 0.006) and 1.8 times more likely to improve on the CSS (95% CI, 1.1, 3.1; P = 0.020) compared with patients undergoing revision surgery. CONCLUSION: In this prospective, multi-institutional study, most patients experienced clinically significant improvement across multiple QOL outcomes after ESS. Specific patient characteristics provided prognostic value with regard to outcomes.

An index for assessing blindness in a multi-centre clinical trial: disulfiram for alcohol cessation--a VA cooperative study.

This paper considers an index to assess the success of blinding with application to a clinical trial of disulfiram. The index increases as the success of blinding increases, accounts for uncertain responses, and is scaled to an interval of 0.0 to 1.0, 0.0 being complete lack of blinding and 1.0 being complete blinding.

Predictors of Olfactory Dysfunction in Patients With Chronic Rhinosinusitis

Objectives: To measure the prevalence of and identify clinical characteristics associated with poor olfactory function in a large cohort of patients with chronic rhinosinusitis (CRS).

A 5-year prospective study of diabetes and hearing loss in a veteran population.

Hypothesis: Veterans with diabetes will have significantly greater hearing loss than nondiabetic veterans. Background: The association between diabetes and hearing loss remains unclear despite the volume of research that has been devoted to the question. Often, differences in hearing thresholds between diabetic and nondiabetic patients are confounded by age and noise exposure. Methods: In this 5-year prospective study, 342 diabetic veterans and 352 nondiabetic veterans from the Portland VA Medical Center in Oregon were tested on a variety of audiometric measures, including pure-tone thresholds. Results: Age and noise exposure were accounted for in the analyses. There was a trend toward greater hearing loss in diabetic patients 60 years of age and younger across the frequency range. These differences were statistically significant only in the highest frequencies tested (10, 12.5, 14, and 16 kHz). The effects of both diabetes and noise exposure on high-frequency hearing thresholds were dependent on age. For patients older than 60 years, the mean thresholds were not significantly different. Conclusion: These results suggest that diabetic patients 60 years old or younger may show early high-frequency hearing loss similar to early presbycusis. After age 60, difference in hearing loss between diabetic and nondiabetic patients was reduced.

Impact of Aspirin Intolerance on Outcomes of Sinus Surgery

Objectives: To compare objective and quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) in aspirin (ASA)‐tolerant patients and ASA‐intolerant patients over intermediate and long‐term follow‐up.

Neuropsychological Screening for Cognitive Impairment Using Computer-Assisted Tasks:

The aim of this study was to validate a computer-assisted screening battery for classifying patients into two groups, those with and without cognitive impairment. Participants were all patients referred to the neuropsychology clinics at four VA medical centers during a 1-year period. Patients meeting the study inclusionary criteria (N = 252) were administered the Neurobehavioral Evaluation System-3 (NES3) computer-assisted battery. A detailed neuropsychological examination was carried out by an experienced neuropsychologist, who diagnosed the patient as cognitively impaired or not impaired. The neuropsychologists diagnosis was the gold standard. Recursive partitioning analyses yielded several classification procedures using the NES3 data to predict the gold standard. These procedures produced a set of six NES3 tasks that provide good sensitivity and specificity in predicting diagnosis. Sensitivity and specificity for the least random classification procedure were 0.87 and 0.67, respectively. The results suggest that computer-assisted screening methods are a promising means of triaging patients.

Endoscopic and Quality‐of‐Life Outcomes After Revision Endoscopic Sinus Surgery

Objectives: First, to examine the impact of endoscopic sinus surgery (ESS) on endoscopic and quality‐of‐life (QOL) outcomes after revision ESS as compared to primary ESS. Second, to evaluate whether or not other risk factors and/or co‐morbidities influence the relationship between revision surgery status and outcomes of ESS.