Impairment in HDL function associated with obesity and elevated serum triglyceride (TG) may be a major contributor to risk of coronary heart disease (CHD) in obese patients, yet mechanisms by which changes in metabolism impair HDL function are not well defi ned ( 1-6 ). Increased TGs in the form of VLDL give rise to low levels of HDL in part due to the actions of cholesteryl ester transfer protein (CETP), which shuttles TG and cholesteryl esters between serum lipoproteins. Because of lipid exchange, elevated serum VLDL leads to TG enrichment of HDL. This TG enrichment reduces the affinity of apolipoprotein A1 (apoA1) for cholesterol, promotes clearance of apoA1, and decreases HDL particle number ( 1, 3, 7 ). In addition, changes in the function of HDL related to infl ammation, coagulation, and reverse cholesterol transport are associated with obesity and metabolic diseases. HDL proteomics have revealed changes in apolipoproteins, infl ammatory proteins, and coagulation proteins in individuals with known Abstract Mechanisms underlying changes in HDL composition caused by obesity are poorly defi ned, partly because mice lack expression of cholesteryl ester transfer protein (CETP), which shuttles triglyceride and cholesteryl ester between lipoproteins. Because menopause is associated with weight gain, altered glucose metabolism, and changes in HDL, we tested the effect of feeding a high-fat diet (HFD) and ovariectomy (OVX) on glucose metabolism and HDL composition in CETP transgenic mice. After OVX, female CETP-expressing mice had accelerated weight gain with HFDfeeding and impaired glucose tolerance by hyperglycemic clamp techniques, compared with OVX mice fed a low-fat diet (LFD). Sham-operated mice (SHAM) did not show HFDinduced weight gain and had less glucose intolerance than OVX mice. Using shotgun HDL proteomics, HFD-feeding in OVX mice had a large effect on HDL composition, including increased levels of apoA2, apoA4, apoC2, and apoC3, proteins involved in TG metabolism. These changes were associated with decreased hepatic expression of SR-B1, ABCA1, and LDL receptor, proteins involved in modulating the lipid content of HDL. In SHAM mice, there were minimal changes in HDL composition with HFD feeding. These studies suggest that the absence of ovarian hormones negatively infl uences the response to high-fat feeding in terms of glucose tolerance and HDL composition. CETP-expressing mice may represent a useful model to defi ne how metabolic changes affect HDL composition and function.
BackgroundRepetitive laboratory testing in stable patients is low-value care. Electronic health record (EHR)-based interventions are easy to disseminate but can be restrictive.ObjectiveTo evaluate the effect of a minimally restrictive EHR-based intervention on utilisation.SettingOne year before and after intervention at a 600-bed tertiary care hospital. 18 000 patients admitted to General Medicine, General Surgery and the Intensive Care Unit (ICU).InterventionProviders were required to specify the number of times each test should occur instead of being able to order them indefinitely.MeasurementsFor eight tests, utilisation (number of labs performed per patient day) and number of associated orders were measured.ResultsUtilisation decreased for some tests on all services. Notably, complete blood count with differential decreased 9% (p<0.001) on General Medicine and 21% (p<0.001) in the ICU.ConclusionsRequiring providers to specify the number of occurrences of labs changes significantly reduces utilisation in some cases.
Objective Cardiac surgery intensive care unit (ICU) characteristics and clinician staffing patterns have not been well characterized. We sought to describe Pennsylvania cardiac ICUs and to determine whether ICU characteristics are associated with mortality in the 30 days after cardiac surgery. Design From 2012–2013, we conducted a survey of cardiac surgery ICUs in Pennsylvania to assess ICU structure, care practices, and clinician staffing patterns. ICU data were linked to an administrative database of cardiac surgery patient discharges. We used logistic regression to measure the association between ICU variables and death in 30 days. Setting Cardiac surgery ICUs in Pennsylvania. Patients Patients having coronary artery bypass grafting (CABG) and/or cardiac valve repair or replacement from 2009 to 2011. Interventions None Measurements and Main Results Out of 57 cardiac surgical ICUs in Pennsylvania, 43 (75.4%) responded to the facility survey. Rounds included respiratory therapists in 26/43 (60.5%) and pharmacists in 23/43 (53.5%). 26.8% (11/41) reported that at least 2/3 of their nurses had a BSN degree. Advanced practice providers were present in most of the ICUs (37/43, 86.0%), but residents (8/42, 18.6%) and fellows (7/43, 16.3%) were not. Daytime intensivists were present in 48.8% (21/43) of responding ICUs; 18.6% (8/43) had nighttime intensivists. Among 29,449 patients, there was no relationship between mortality and nurse ICU experience, presence of any intensivist, or absence of residents after risk adjustment. To exclude patients who may have undergone transcatheter aortic valve replacement, we conducted a subgroup analysis of patients undergoing only CABG, and results were similar. Conclusions Pennsylvania cardiac surgery ICUs have variable structures, care practices, and clinician staffing, although none of these are statistically significantly associated with mortality in the 30 days following surgery after adjustment.
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