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1.  Etomidate, Adrenal Function, and Mortality in Critically Ill Patients 
Respiratory care  2013;58(4):639-646.
BACKGROUND
In critically ill patients, induction with etomidate is hypothesized to be associated with an increased risk of mortality. Previous randomized studies suggest a modest trend toward an increased risk of death among etomidate recipients; however, this relationship has not been measured with great statistical precision. We aimed to test whether etomidate is associated with risk of hospital mortality and other clinical outcomes in critically ill patients.
METHODS
We conducted a retrospective cohort study from January 1, 2001, to December 31, 2005, of 824 subjects requiring mechanical ventilation, who underwent adrenal function testing in the ICUs of 2 academic medical centers. The primary outcome was in-hospital mortality, comparing subjects given etomidate (n = 452) to those given an alternative induction agent (n = 372). The secondary outcome was diagnosis of critical illness-related corticosteroid insufficiency following etomidate exposure.
RESULTS
Overall mortality was 34.3%. After adjustment for age, sex, and baseline illness severity, the relative risk of death among the etomidate recipients was higher than that of subjects given an alternative agent (relative risk 1.20, 95% CI 0.99–1.45). Among subjects whose adrenal function was assessed within the 48 hours following intubation, the adjusted risk of meeting the criteria for critical illness-related corticosteroid insufficiency was 1.37 (95% CI 1.12–1.66), comparing etomidate recipients to subjects given another induction agent.
CONCLUSIONS
In this study of critically ill patients requiring endotracheal intubation, etomidate administration was associated with a trend toward a relative increase in mortality, similar to the collective results of smaller randomized trials conducted to date. If a small relative increased risk is truly present, though previous trials have been underpowered to detect it, in absolute terms the number of deaths associated with etomidate in this high-risk population would be considerable. Large, prospective controlled trials are needed to finalize the role of etomidate in critically ill patients.
doi:10.4187/respcare.01956
PMCID: PMC4126750  PMID: 22906838
sepsis; ICU; mortality; etomidate; adrenal function; rapid sequence induction
2.  Racial and Ethnic Differences in Adjuvant Hormonal Therapy Use 
Journal of Women's Health  2012;21(9):950-958.
Abstract
Background
In the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial/ethnic differences in adjuvant hormonal therapy use among women aged 18–64 years, diagnosed with hormone receptor-positive breast cancer, using data collected by the Northern California Breast Cancer Family Registry (NC-BCFR), and explored changes in use over time.
Methods
Odds ratios (OR) comparing self-reported ever-use by race/ethnicity (African American, Hispanic, non-Hispanic white vs. Asian American) were estimated using multivariable adjusted logistic regression. Analyses were stratified by recruitment phase (phase I, diagnosed January 1995–September 1998, phase II, diagnosed October 1998–April 2003) and genetic susceptibility, as cases with increased genetic susceptibility were oversampled.
Results
Among 1385 women (731 phase I, 654 phase II), no significant racial/ethnic differences in use were observed among phase I or phase II cases. However, among phase I cases with no susceptibility indicators, African American and non-Hispanic white women were less likely than Asian American women to use hormonal therapy (OR 0.20, 95% confidence interval [CI]0.06–0.60; OR 0.40, CI 0.17–0.94, respectively). No racial/ethnic differences in use were observed among women with 1+ susceptibility indicators from either recruitment phase.
Conclusions
Racial/ethnic differences in adjuvant hormonal therapy use were limited to earlier diagnosis years (phase I) and were attenuated over time. Findings should be confirmed in other populations but indicate that in this population, treatment disparities between African American and Asian American women narrowed over time as adjuvant hormonal treatments became more commonly prescribed.
doi:10.1089/jwh.2011.3254
PMCID: PMC3430474  PMID: 22731764
3.  Sibling History of Myocardial Infarction or Stroke and Risk of Cardiovascular Disease in the Elderly: The Cardiovascular Health Study 
Annals of epidemiology  2009;19(12):858-866.
PURPOSE
To assess the relationship between sibling history of myocardial infarction (MI) or stroke with cardiovascular disease (CVD) and risk factors in older adults.
METHODS
Prospective cohort study of 5,888 older adults participating to the Cardiovascular Health Study (CHS). History of MI and stroke in siblings was obtained by self-report. Participants with positive sibling histories were compared to those with negative histories to determine if prevalent or incident disease (coronary heart disease [CHD], MI, stroke, angina), subclinical CVD (carotid wall thickness, left ventricular mass, hypertension, diabetes, ankle brachial index), CVD risk factors differed between groups.
RESULTS
More than 91 percent (n=5,383) of CHS participants reported at least one sibling. Sibling history of MI was associated with increased disease prevalence (CHD, MI, angina) and incidence (CHD, angina). Sibling history of stroke was associated with increased disease prevalence (CHD, angina). Sibling history of either MI or stroke was associated with increased disease prevalence and incidence for CHD, MI and angina, more subclinical disease, and a higher CVD risk profile.
CONCLUSIONS
Sibling history of MI and stroke were markers of higher CVD risk status even in older adults. Of clinical importance, participants with positive sibling history have numerous risk factors amenable to intervention.
doi:10.1016/j.annepidem.2009.07.095
PMCID: PMC2806844  PMID: 19944349
Epidemiology; Cardiovascular diseases; Risk Factors; Atherosclerosis; Lifestyle
4.  Associations of cardiovascular risk factors, carotid intima-media thickness and left ventricular mass with inter-adventitial diameters of the common carotid artery: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2011;218(2):344-349.
Background
Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors.
Methods
IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass.
Results
Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a one mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A one gm difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. LV mass was independently associated with IAD after adjusting for cardiovascular risk factors and IMT. These associations were slightly different for men and women.
Conclusions
Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes.
doi:10.1016/j.atherosclerosis.2011.05.033
PMCID: PMC3186064  PMID: 21726862
carotid arteries; ultrasonics; hypertrophy; magnetic resonance imaging; remodeling; risk factors; left ventricle
5.  Changes in Carotid Intima-Media Thickness During the Cardiac Cycle: The Multi-Ethnic Study of Atherosclerosis 
Background
Common carotid artery intima-media thickness (IMT), a measure of subclinical cardiovascular disease, changes during the cardiac cycle. The magnitude of this effect and its implications have not been well studied.
Methods and Results
Far-wall IMT measurements of the right common carotid artery were measured at end diastole and peak systole in 5633 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable regression models were generated with end-diastolic IMT, peak-systolic IMT, and change in IMT during the cardiac cycle as dependent variables and traditional cardiovascular risk factors as independent variables. The average age of our population was 61.9 (45 to 84) years. Average change in carotid IMT during the cardiac cycle was 0.041 mm (95% confidence interval: 0.039 to 0.042 mm), with a mean IMT of 0.68 mm. End-diastolic IMT and peak-systolic IMT were similarly associated with risk factors. In a fully adjusted model, change in carotid IMT during the cardiac cycle was associated with ethnicity and pulse pressure (P=0.001) and not age, sex, or other risk factors. Chinese and Hispanics had less of a change in IMT than did non-Hispanic whites. With peak-systolic IMT reference values used as normative data, 31.3% more individuals were classified as being in the upper quartile of IMT and at high risk for cardiovascular disease than would be expected when IMT is measured at end diastole.
Conclusions
Measurable differences in IMT are seen during the cardiac cycle. This affects the interpretation of IMT measurements used for cardiovascular risk assessment, given published normative data with IMT measured at peak systole.
Clinical Trial Registration
URL: www.ClinicalTrials.gov. Unique identifier: NCT00063440. (J Am Heart Assoc. 2012;1:e001420 doi: 10.1161/JAHA.112.001420.)
doi:10.1161/JAHA.112.001420
PMCID: PMC3487346  PMID: 23130162
atherosclerosis; blood pressure; carotid arteries; diastole; epidemiology; risk factors; systole; ultrasonics
6.  Association between hospital volume and network membership and an analgesia, sedation and delirium order set quality score: a cohort study 
Critical Care  2012;16(3):R106.
Introduction
Protocols for the delivery of analgesia, sedation and delirium care of the critically ill, mechanically ventilated patient have been shown to improve outcomes but are not uniformly used. The extent to which elements of analgesia, sedation and delirium guidelines are incorporated into order sets at hospitals across a geographic area is not known. We hypothesized that both greater hospital volume and membership in a hospital network are associated with greater adherence of order sets to sedation guidelines.
Methods
Sedation order sets from all nonfederal hospitals without pediatric designation in Washington State that provided ongoing care to mechanically ventilated patients were collected and their content systematically abstracted. Hospital data were collected from Washington State sources and interviews with ICU leadership in each hospital. An expert-validated score of order set quality was created based on the 2002 four-society guidelines. Clustered multivariable linear regression was used to assess the relationship between hospital characteristics and the order set quality score.
Results
Fifty-one Washington State hospitals met the inclusion criteria and all provided order sets. Based on expert consensus, 21 elements were included in the analgesia, sedation and delirium order set quality score. Each element was equally weighted and contributed one point to the score. Hospital order set quality scores ranged from 0 to 19 (median = 8, interquartile range 6 to 14). In multivariable analysis, a greater number of acute care days (P = 0.01) and membership in a larger hospital network (P = 0.01) were independently associated with a greater quality score.
Conclusions
Hospital volume and membership in a larger hospital network were independently associated with a higher quality score for ICU analgesia, sedation and delirium order sets. Further research is needed to determine whether greater order-set quality is associated with improved outcomes in the critically ill. The development of critical care networks might be one strategy to improve order set quality scores.
doi:10.1186/cc11390
PMCID: PMC3580663  PMID: 22709540
7.  Racial Disparities Among Lung Cancer Patients Recommended Operative Therapy 
Hypothesis
Healthcare system/provider biases and differences in patient characteristics are thought to be prevailing factors underlying racial disparities. The influence of these factors on the receipt of care would likely be mitigated among patients recommended optimal therapy. We hypothesized that there would be no significant evidence of racial disparities among early-stage lung cancer patients recommended surgical therapy.
Design
Retrospective cohort study.
Patients and Setting
Patients within the Surveillance, Epidemiology, and End-Results-Medicare database diagnosed with stage I or II lung cancer between 1992 and 2002 (follow-up through 2005).
Main Outcome Measures
Receipt of lung resection and overall survival.
Results
Among 17,739 patients recommended surgical therapy—mean (SD) age 75 (5) years, 89% white, 6% black—blacks less frequently underwent resection compared to whites (69% versus 83%, p<0.001). After adjustment, black race was associated with a lower odds of receiving surgical therapy (OR 0.43, 99% CI 0.36-0.52). Unadjusted 5-year survival rates were lower for blacks compared to whites (36% versus 42%, p<0.001). After adjustment, there was no significant association between race and death (HR 1.03, 99% CI 0.92-1.14) despite a 14% difference in receipt of optimal therapy.
Conclusions
Even among patients recommend surgical therapy, blacks underwent lung resection less often then whites. Unexpectedly, racial differences in the receipt of optimal therapy did not appear to affect outcomes. These findings suggest that distrust, beliefs and perceptions about lung cancer and its treatment, and limited access to care (despite insurance) might have a more dominant role in perpetuating racial disparities than previously recognized.
doi:10.1001/archsurg.2008.519
PMCID: PMC2688646  PMID: 19153319
8.  The relationship of bottle feeding and other sucking behaviors with speech disorder in Patagonian preschoolers 
BMC Pediatrics  2009;9:66.
Background
Previous studies have shown that children's nonnutritive sucking habits may lead to delayed development of their oral anatomy and functioning. However, these findings were inconsistent. We investigated associations between use of bottles, pacifiers, and other sucking behaviors with speech disorders in children attending three preschools in Punta Arenas (Patagonia), Chile.
Methods
Information on infant feeding and sucking behaviors, age starting and stopping breast- and bottle-feeding, pacifier use, and other sucking behaviors, was collected from self-administered questionnaires completed by parents. Evaluation of speech problems was conducted at preschools with subsequent scoring by a licensed speech pathologist using age-normative standards.
Results
A total of 128 three- to five-year olds were assessed, 46% girls and 54% boys. Children were breastfed for an average of 25.2 (SD 9.6) months and used a bottle 24.4 (SD 15.2) months. Fifty-three children (41.7%) had or currently used a pacifier for an average of 11.4 (SD 17.3) months; 23 children (18.3%) were reported to have sucked their fingers. Delayed use of a bottle until after 9 months appeared to be protective for subsequent speech disorders. There was less than a one-third lower relative odds of subsequent speech disorders for children with a delayed use of a bottle compared to children without a delayed use of a bottle (OR: 0.32, 95% CI: 0.10-0.98). A three-fold increase in relative odds of speech disorder was found for finger-sucking behavior (OR: 2.99, 95% CI: 1.10-8.00) and for use of a pacifier for 3 or more years (OR: 3.42, 95% CI: 1.08-10.81).
Conclusion
The results suggest extended use of sucking outside of breastfeeding may have detrimental effects on speech development in young children.
doi:10.1186/1471-2431-9-66
PMCID: PMC2773774  PMID: 19845936
9.  Effect of Intensive Care Unit Organizational Model and Structure on Outcomes in Patients with Acute Lung Injury 
Rationale: Prior studies supported an association between intensive care unit (ICU) organizational model or staffing patterns and outcome in critically ill patients.
Objectives: To examine the association of closed versus open models with patient mortality across adult ICUs in King County (WA).
Methods: Cohort study of patients with acute lung injury (ALI).
Measurements and Main Results: ICU structure, organization, and patient care practices were assessed using self-administered mail questionnaires completed by the medical director and nurse manager. We defined closed ICUs as units that required patient transfer to or mandatory patient comanagement by an intensivist and open ICUs as those relying on other organizational models. Outcomes were obtained from the King County Lung Injury Project, a population-based cohort of patients with ALI. The main endpoint was hospital mortality. Of 24 eligible ICUs, 13 ICUs were designated closed and 11 open. Complete survey data were available for 23 (96%) ICUs. Higher physician and nurse availability was reported in closed versus open ICUs. A total of 684 of 1,075 (63%) of patients with ALI were cared for in closed ICUs. After adjusting for potential confounders, patients with ALI cared for in closed ICUs had reduced hospital mortality (adjusted odds ratio, 0.68; 95% confidence interval, 0.53, 0.89; P = 0.004). Consultation by a pulmonologist in open ICUs was not associated with improved mortality (adjusted odds ratio, 0.94; 95% confidence interval, 0.74, 1.20; P = 0.62). These findings were robust for varying assumptions about the study population definition.
Conclusions: Patients with ALI cared for in a closed-model ICU have reduced mortality. These data support recommendations to implement structured intensive care in the United States.
doi:10.1164/rccm.200701-165OC
PMCID: PMC1994237  PMID: 17556721
intensive care unit; intensivist; outcome; practice patterns; Leapfrog Group
10.  Intensive insulin therapy and mortality in critically ill patients 
Critical Care  2008;12(1):R29.
Introduction
Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.
Methods
We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I.
Results
Insulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III.
Conclusion
A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.
doi:10.1186/cc6807
PMCID: PMC2374630  PMID: 18312617

Results 1-10 (10)