Citations

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti–human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

Abstract —Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary endothelial function, endothelial NO synthase (eNOS) expression, and oxidative stress in experimental hypercholesterolemia (HC) in the absence of cholesterol lowering. Pigs were randomized to 3 experimental groups: normal diet (N group), high cholesterol diet (HC group), and HC diet with simvastatin (HC+S group) for 12 weeks. Low density lipoprotein cholesterol was similarly increased in the HC and HC+S groups compared with the N group. In vitro analysis of coronary large- and small-vessel endothelium-dependent vasorelaxation was performed. The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group (32.3±1.2% versus 42.9±1.6%, respectively; P <0.0001). This attenuation was significantly reversed in the HC+S group (38.7±1.5%, P <0.005 versus HC group). The maximal vasorelaxation to substance P was significantly attenuated in the HC group compared with the N group (50.5±11.9% versus 79.3±5.3%, respectively; P <0.05). This attenuated response was normalized in the HC+S group (74.9±4.1%, P <0.05 versus HC group). The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group (71.9±4.9% versus 96.8±1.34%, respectively; P <0.005). This was reversed in the HC+S group (98.4±0.6%, P <0.0001 versus HC group). Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group, with normalization in the HC+S group. Elevation of plasma F 2 -isoprostanes and thiobarbituric acid–reactive substances, markers of oxidative stress, occurred in the HC compared with the N group. These changes were reversed in the HC+S group. In summary, simvastatin preserves endothelial function in coronary epicardial vessels and arterioles in experimental HC (in the absence of cholesterol lowering) in association with an increase in coronary eNOS levels and a decrease in oxidative stress. These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Context: The delivery of end-of-life care (EOLC) in the intensive care unit (ICU) varies widely among medical care providers. The differing opinions of nurses and physicians regarding EOLC may help identify areas of improvement. Objective: To explore the differences of physicians and nurses on EOLC in the ICU and how these differences vary according to self-reported proficiency level and primary work unit. Design: Cross-sectional survey of 69 ICU physicians and 629 ICU nurses. Setting: Single tertiary care academic medical institution. Results: A total of 50 physicians (72%) and 331 nurses (53%) participated in the survey. Significant differences between physicians and nurses were noted in the following areas: ability to safely raise concerns, do not resuscitate (DNR) decision making, discussion of health care directives, timely hospice referral, spiritual assessment documentation, utilization of social services, and the availability of EOLC education. In every domain of EOLC, physicians reported a more positive perception than nurses. Additional differences were noted among physicians based on experience, as well as among nurses based on their primary work unit and self-reported proficiency level. Conclusions: Even with an increased focus on improving EOLC, significant differences continue to exist between the perspectives of nurses and physicians, as well as physicians among themselves and nurses among themselves. These differences may represent significant barriers toward providing comprehensive, consistent, and coordinated EOLC in the ICU.

This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment and/or dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor determining prevalence estimates of Alzheimer's disease (AD) is the severity of cognitive impairment used as a threshold to define cases. Studies that require a level of cognitive impairment in which persons are unable to provide self‐care will have much lower estimates than the studies aimed at identifying persons in the earliest stages of AD. There are limited autopsy data from the aforementioned epidemiological studies to address accuracy in the diagnosis of etiological subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community‐based cohort studies show that many persons with mild cognitive impairment and also some persons without dementia or mild cognitive impairment meet pathological criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiological studies.

Abstract Background: Genetic susceptibility for cancer can differ substantially among families. We use trait-related covariates to identify a genetically homogeneous subset of families with the best evidence for linkage in the presence of heterogeneity. Methods: We performed a genome-wide linkage screen in 93 families. Samples and data were collected by the familial lung cancer recruitment sites of the Genetic Epidemiology of Lung Cancer Consortium. We estimated linkage scores for each family by the Markov chain Monte Carlo procedure using SimWalk2 software. We used ordered subset analysis (OSA) to identify genetically homogenous families by ordering families based on a disease-associated covariate. We performed permutation tests to determine the relationship between the trait-related covariate and the evidence for linkage. Results: A genome-wide screen for lung cancer loci identified strong evidence for linkage to 6q23–25 and suggestive evidence for linkage to 12q24 using OSA, with peak logarithm of odds (LOD) scores of 4.19 and 2.79, respectively. We found other chromosomes also suggestive for linkages, including 5q31–q33, 14q11, and 16q24. Conclusions: Our OSA results support 6q as a lung cancer susceptibility locus and provide evidence for disease linkage on 12q24. This study further increased our understanding of the inheritability for lung cancer. Validation studies using larger sample size are needed to verify the presence of several other chromosomal regions suggestive of an increased risk for lung cancer and/or other cancers. Impact: OSA can reduce genetic heterogeneity in linkage study and may assist in revealing novel susceptibility loci. Cancer Epidemiol Biomarkers Prev; 19(12); 3157–66. ©2010 AACR.

Background— Infection is a serious complication of cardiovascular implantable electronic device (CIED) placement and requires device removal for attempted cure. Methods and Results— We studied the rate, risk factors, and outcomes of CIED infection in 74 consecutive patients with bacteremia caused by Gram-positive cocci (GPC) other than Staphylococcus aureus between 2001 and 2007. CIED infection was defined as the presence of signs of infection at the generator site, lead vegetations seen on echocardiography, or microbiological growth from device cultures. Twenty-two (30%) of 74 patients with non– S aureus GPC bacteremia had CIED infections. Coagulase-negative staphylococci (CoNS) accounted for 73% of CIED infections. The rate of CIED infection in patients with CoNS bacteremia was almost 2-fold that of non-CoNS GPC bacteremia (36% versus 20%, P =0.13). The number of leads, the presence of abandoned leads, and prior generator replacement were associated with CIED infection. Among 33 patients without identifiable CIED infection at initial evaluation who did not undergo device removal, 5 (15%) had relapsing bacteremia within 12 weeks of completing antibiotic therapy. CoNS accounted for all relapses, and none had evidence of CIED infection at relapse. Conclusions— Patients with a CIED and bacteremia caused by GPC other than S aureus frequently had evidence of underlying CIED infection on clinical evaluation that included transesophageal echocardiography. This was particularly true among those with CoNS bacteremia. No evidence of underlying CIED infections was identified in the subgroup of patients who did not have manifestations of CIED infection on initial evaluation but subsequently had relapsing bacteremia caused by CoNS.

Background— Studies report a protective effect of higher attained educational level (AEL) on cardiovascular outcomes. However, most of these studies have been conducted in high-income countries (HICs) and lack representation from low- and middle-income countries (LMICs), which bear >80% of the global burden of cardiovascular disease. Methods and Results— The Reduction of Atherothrombosis for Continued Health (REACH) Registry is a prospective study of 67 888 subjects with either established atherothrombotic (coronary, cerebrovascular, and/or peripheral arterial) disease or multiple atherothrombotic risk factors enrolled from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9 to 12 years, trade or technical school, and university) was self-reported for 61 332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk factors and the rate of incident cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL groups, stratified by sex and world region (LMICs or HICs). Educational attainment was inversely associated with age and diabetes mellitus and directly associated with hypercholesterolemia in all subjects. However, for other risk factors such as obesity, smoking, hypertension, and baseline burden of vascular disease, AEL was protective (inversely associated) in HICs but not protective in LMICs. The protective effect of greater AEL on incident cardiovascular events was strongest in men from HICs ( P <0.0001), more modest in women from HICs ( P =0.0026) and in men from LMICs ( P =0.082), and essentially absent in women from LMICs ( P =0.32). Conclusion— In contrast to HICs, higher AEL may not be protective against cardiovascular events in LMICs, particularly in women.