Assessing the Informed Consent Skills of Emergency Medicine Resident Physicians.

BACKGROUND: Informed consent (IC) is an essential component of shared medical decision making between patients and providers in emergency medicine (EM). The basic components required for adequate consent are well described, yet little is published investigating whether EM residents demonstrate adequate IC skills. OBJECTIVE: The objectives were to assess the ability of EM residents to obtain IC for an invasive emergency procedure using a novel assessment tool and to assess reliability and validity of the tool. METHODS: This was an observational study in which participants were initially blinded to the primary objectives of the study. Each participant conducted a video-recorded history and physical examination with a standardized patient, requiring tube thoracostomy due to spontaneous pneumothorax. Two faculty EM physicians independently reviewed the videos and evaluated the participants' IC skills. First, they gave an overall impression of whether IC was obtained; they then evaluated the participants using a 30-point scoring tool based on the five elements of IC (decision-making capacity, disclosure, voluntariness, understanding, and physician recommendation). Upon all participants' case completion, we revealed the primary objectives and gave participants the option to withdraw from the study. Descriptive statistics and kappa coefficient were generated from the data collected. RESULTS: Twenty-two residents completed the study. None withdrew from the study after the primary objectives were revealed. Twenty residents (91%) obtained adequate IC based on both reviewers' overall impression. One disagreement occurred between reviewers (κ = 0.64). The mean IC score on a 30-point scale was 18.5 ± 0.5. CONCLUSIONS: In a simulated setting, most EM residents at this training program possess the knowledge and skills necessary to obtain IC prior to an invasive procedure. The assessment tool appears reliable and demonstrates construct validity.

Adipocytokines as features of the metabolic syndrome determined using confirmatory factor analysis.

PURPOSE: Confirmatory factor analysis (CFA) was used to test the hypothesis whether adipocytokines are associated with the risk factor cluster that characterizes the metabolic syndrome (MetS). METHODS: Data from 134 nondiabetic subjects were analyzed using CFA. Insulin sensitivity (SI) was quantified using intravenous glucose tolerance tests, visceral fat area by computed tomography and fasting high-density lipoprotein, triglycerides, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A (SAA), tumor necrosis factor (TNF)-α, adiponectin, resistin, leptin, interleukin (IL)-6, C-reactive protein (CRP), and plasminogen activator inhibitor (PAI)-1 were measured. RESULTS: The basic model representing the MetS included six indicators comprising obesity, SI, lipids, and hypertension, and demonstrated excellent goodness of fit. Using multivariate analysis, MCP-1, SAA, and TNF-α were not independently associated with any of the MetS variables. Adiponectin, resistin, leptin, CRP, and IL-6 were associated with at least one of the risk factors, but when added to the basic model decreased all goodness-of-fit parameters. PAI-1 was associated with all cardiometabolic factors and improved goodness-of-fit compared with the basic model. CONCLUSIONS: Addition of PAI-1 increased the CFA model goodness of fit compared with the basic model, suggesting that this protein may represent an added feature of the MetS.

Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity.

BACKGROUND: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. OBJECTIVE: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. DESIGN: Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. RESULTS: The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR > OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03), and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite. CONCLUSIONS: Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.

Comparative Effectiveness and Toxicity of Statins Among HIV-Infected Patients.

BACKGROUND: dyslipidemia is common and is often treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Little is known about the comparative effectiveness of statins among human immunodeficiency virus (HIV)-infected patients. This study compared the effectiveness and toxicity of statins among HIV-infected patients in clinical care. METHODS: we conducted a retrospective cohort study of patients starting their initial statin medications at 2 large HIV clinics (N = 700). The primary observation was change in lipid levels during statin therapy. Secondary observations included whether individualized National Cholesterol Education Program (NCEP) goals for low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) levels were reached, and toxicity rates. We used linear regression to examine change in lipid levels, controlling for baseline lipid values and demographic and clinical characteristics. We conducted secondary analyses using propensity scores to address confounding by indication. RESULTS: the most commonly prescribed statins were atorvastatin (N = 303), pravastatin (N = 280), and rosuvastatin (N = 95). One year after starting a statin therapy, patients who received atorvastatin or rosuvastatin had significantly greater decreases in total cholesterol, LDL-C, and non-HDL-C than patients on pravastatin. The likelihood of reaching NCEP goals for LDL-C levels was higher with the use of rosuvastatin (OR 2.1; P = .03) and atorvastatin (odds ratio [OR], 2.1; P = .001) compared with that of pravastatin. The likelihood of reaching NCEP goals for non-HDL-C levels was higher for rosuvastatin (OR 2.3; P = .045) but not atorvastatin (OR, 1.5; P = .1) compared with pravastatin. Toxicity rates were similar for all 3 statins: 7.3% for atorvastatin, 6.1% for pravastatin, and 5.3% for rosuvastatin. CONCLUSIONS: our findings suggest that atorvastatin and rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients with dyslipidemia, due to greater declines in total cholesterol, LDL-C, and non-HDL-C, with similar lower toxicity rates.

Association of combinations of lipid parameters with carotid intima-media thickness and coronary artery calcium in the MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The purpose of this study was to determine the association of combinations of lipid parameters with subclinical atherosclerosis. BACKGROUND: Carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) are significantly associated with incident cardiovascular disease (CVD). The association between common dyslipidemias (combined hyperlipidemia, [simple] hypercholesterolemia, dyslipidemia of metabolic syndrome, isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipemia, and CIMT and CAC has not been previously examined. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) participants were White, Chinese, African-American, or Hispanic adults without clinical CVD. Subjects with diabetes mellitus or who were receiving lipid-lowering therapy were excluded. Every participant was classified into only 1 of 6 groups defined by specific low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride cut points. Multivariate linear and relative risk regressions evaluated the cross-sectional associations with CIMT and CAC after adjusting for CVD risk factors. Interactions with race, sex, and high-sensitivity C-reactive protein were evaluated for CIMT and CAC outcomes. RESULTS: Among 4,792 participants, only those with combined hyperlipidemia and hypercholesterolemia demonstrated both increased common CIMT (combined hyperlipidemia 0.048 mm thicker, 95% confidence interval [CI]: 0.016 to 0.080 mm; hypercholesterolemia 0.048 mm thicker, 95% CI: 0.029 to 0.067 mm) and internal CIMT (combined hyperlipidemia 0.120 mm thicker, 95% CI: 0.032 to 0.208 mm; and hypercholesterolemia 0.161 mm thicker, 95% CI: 0.098 to 0.223 mm) as well as increased risk for prevalent CAC (combined hyperlipidemia relative risk: 1.22, 95% CI: 1.08 to 1.38; hypercholesterolemia relative risk: 1.22, 95% CI: 1.11 to 1.34) compared with normolipemia. The interactions between lipid parameters and race, sex, or high-sensitivity C-reactive protein were not significant for any outcomes. CONCLUSIONS: Combined hyperlipidemia and simple hypercholesterolemia were associated with increased CIMT and prevalent CAC in a relatively healthy multiethnic population.

Low clusterin levels in high-density lipoprotein associate with insulin resistance, obesity, and dyslipoproteinemia.

OBJECTIVE: To determine whether obesity and insulin resistance associate with changes in the protein content of high-density lipoprotein (HDL) in 2 different groups of men by using targeted proteomics. METHODS AND RESULTS: Insulin resistance and obesity are hallmarks of type 2 diabetes mellitus and the metabolic syndrome, which confer an increased risk of cardiovascular disease. Recent studies suggest that the protein cargo of HDL makes important contributions to the lipoprotein's cardioprotective effects. In a discovery study, we used isotope dilution mass spectrometry to quantify the relative concentrations of 5 proteins previously implicated in HDL's cardioprotective effects in 3 groups of healthy subjects: lean insulin-sensitive, lean insulin-resistant, and obese insulin-resistant individuals. We validated our findings in a different group of subjects. The clusterin concentration in HDL strongly and negatively associated with insulin resistance and body mass index in both populations. HDL clusterin levels were lower in subjects with low HDL and high triglycerides, key components of the metabolic syndrome. There was an inverse correlation between clusterin levels in HDL and very-low-density lipoprotein/low-density lipoprotein. CONCLUSIONS: Clusterin levels in HDL are lower in men with reduced insulin sensitivity, higher body mass index, and an unfavorable lipid profile. Our observations raise the possibility that clusterin depletion contributes to the loss of HDL's cardioprotective properties.

HDL in humans with cardiovascular disease exhibits a proteomic signature.

BACKGROUND: Alterations in protein composition and oxidative damage of high density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of HDL. We tested whether relative levels of proteins in HDL(2) could be used as biomarkers for coronary artery disease (CAD). METHODS: Twenty control and eighteen CAD subjects matched for HDL-cholesterol, age, and sex were studied. HDL(2) isolated from plasma was digested with trypsin and analyzed by high-resolution matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and pattern recognition analysis. RESULTS: Partial least squares discriminant analysis (PLS-DA) of mass spectra clearly differentiated CAD from control subjects with area under the receiver operating characteristic curve (ROC(AUC)) of 0.94. Targeted tandem mass spectrometric analysis of the model's significant features revealed that HDL(2) of CAD subjects contained oxidized methionine residues of apolipoprotein A-I and elevated levels of apolipoprotein C-III. A proteomic signature composed of MALDI-MS signals from apoA-I, apoC-III, Lp(a) and apoC-I accurately classified CAD and control subjects (ROC(AUC)=0.82). CONCLUSIONS: HDL(2) of CAD subjects carries a distinct protein cargo and that protein oxidation helps generate dysfunctional HDL. Moreover, models based on selected identified peptides in MALDI-TOF mass spectra of the HDL may have diagnostic potential.

Endogenous red blood cell membrane fatty acids and sudden cardiac arrest.

Little is known of the associations of endogenous fatty acids with sudden cardiac arrest (SCA). We investigated the associations of SCA with red blood cell membrane fatty acids that are end products of de novo fatty acid synthesis: myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1 n7), vaccenic acid (18:1 n7), stearic acid (18:0), oleic acid (18:1 n9), and a related fatty acid, cis-7 hexadecenoic acid (16:1 n9). We used data from a population-based case-control study where cases, aged 25 to 74 years, were out-of-hospital SCA patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to cases by age, sex, and calendar year, were randomly identified from the community (n = 415). All participants were free of prior clinically diagnosed heart disease. We observed associations of higher red blood cell membrane levels of 16:0, 16:1n-7, 18:1n-7, and 16:1n-9 with higher risk of SCA. In analyses adjusted for traditional SCA risk factors and trans- and n-3 fatty acids, a 1-SD-higher level of 16:0 was associated with 38% higher risk of SCA (odds ratio, 1.38; 95% confidence interval, 1.12-1.70) and a 1-SD-higher level of 16:1n-9 with 88% higher risk (odds ratio, 1.88; 95% confidence interval, 1.27-2.78). Several fatty acids that are end products of fatty acid synthesis are associated with SCA risk. Further work is needed to investigate if conditions that favor de novo fatty acid synthesis, such as high-carbohydrate/low-fat diets, might also increase the risk of SCA.

Improving insulin ordering safely: the development of an inpatient glycemic control program.

This report describes a Glycemic Control Program instituted at an academic regional level-one trauma center. Key interventions included: 1) development of a subcutaneous insulin physician order set, 2) use of a real-time data report to identify patients with out-of-range glucoses, and 3) implementation of a clinical intervention team. Over four years 18,087 patients admitted to non-critical care wards met our criteria as dysglycemic patients. In this population, glycemic control interventions were associated with increased basal and decreased sliding scale insulin ordering. No decrease was observed in the percent of patients experiencing hperglycemia. Hypoglycemia did decline after the interventions (4.3% to 3.6%; p = 0.003). Distinguishing characteristics of this Glycemic Control Program include the use of real-time data to identify patients with out-of-range glucoses and the employment of a single clinician to cover all non-critical care floors.

Red blood cell membrane alpha-linolenic acid and the risk of sudden cardiac arrest.

Higher levels of long-chain n-3 polyunsaturated fatty acids in red blood cell membranes are associated with lower risk of sudden cardiac arrest. Whether membrane levels of alpha-linolenic acid, a medium-chain n-3 polyunsaturated fatty acid, show a similar association is unclear. We investigated the association of red blood cell membrane alpha-linolenic acid with sudden cardiac arrest risk in a population-based case-control study. Cases, aged 25 to 74 years, were out-of-hospital sudden cardiac arrest patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to cases by age, sex, and calendar year, were randomly identified from the community (n = 415). All participants were free of prior clinically diagnosed heart disease. Blood was obtained at the time of cardiac arrest (cases) or at the time of an interview (controls). Higher membrane alpha-linolenic acid was associated with a higher risk of sudden cardiac arrest: after adjustment for matching factors and smoking, diabetes, hypertension, education, physical activity, weight, height, and total fat intake, the odds ratios corresponding to increasing quartiles of alpha-linolenic acid were 1.7 (95% confidence interval [CI], 1.0-3.0), 1.9 (95% CI, 1.1-3.3), and 2.5 (95% CI, 1.3-4.8) compared with the lowest quartile. The association was independent of red blood cell levels of long-chain n-3 fatty acids, trans-fatty acids, and linoleic acid. Higher membrane levels of alpha-linolenic acid are associated with higher risk of sudden cardiac arrest.

Combined hyperlipidemia in relation to race/ethnicity, obesity, and insulin resistance in the Multi-Ethnic Study of Atherosclerosis.

We have asked whether the prevalence of combined hyperlipidemia (CHL) differs by race/ethnicity, obesity, and insulin resistance in a contemporary, multiethnic, US cohort. We determined the prevalence and adjusted odds of CHL in a cohort of 5923 men and women free of clinically recognized cardiovascular disease and diabetes according to race/ethnicity (white, Chinese, African American, and Hispanic), obesity, and insulin resistance. Untreated lipid values were imputed for those on lipid-lowering therapy. Combined hyperlipidemia was defined using age- and sex-specific greater than or equal to 75th percentile cut points for low-density lipoprotein cholesterol and triglycerides obtained from a predominantly white North American population study. Compared with whites, adjusted odds ratios for CHL were 0.48 in African Americans (95% confidence interval [CI], 0.30-0.75), 1.33 in Hispanics (95% CI, 0.93-1.91), and 1.06 in Asians (95% CI, 0.62-1.82). Within the entire population, the adjusted odds of CHL were over 2-fold higher in overweight and obese participants compared with normal-weight participants and more than 4-fold higher in quartiles 2 through 4 of insulin resistance compared with quartile 1. African Americans had lower odds for CHL than whites despite higher body mass index and abdominal adiposity. Hispanics had a nonsignificantly higher trend, and Asians had no significantly different odds than whites. Modest increases in weight and insulin resistance were associated with significantly higher odds of CHL in a multiethnic US population. Further research is needed to determine the most efficacious diet, exercise, and drug management to decrease the risk of CHL and coronary heart disease among racial/ethnic groups in the United States.

The SLIM Study: Slo-Niacin® and Atorvastatin Treatment of Lipoproteins and Inflammatory Markers in Combined Hyperlipidemia.

BACKGROUND: The combination of niacin and statin has proven value in hyperlipidemia management and heart disease prevention. However, the efficacy of the non-prescription time-release niacin, Slo-Niacin®, is little studied alone and not at all with atorvastatin. We gave Slo-Niacin® and atorvastatin, singly and together to determine efficacy on the combined abnormalities of triglyceride, LDL and HDL. METHODS: 42 men and women with LDL-C>130mg/dL HDL-C <45 (men or 55mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/day or incremental doses of Slo-Niacin® to 1500 mg/day. The alternate drug was added in the next 3-month segment. Lipid profiles and transaminases were measured monthly and other measures at baseline and the end of each treatment sequence. RESULTS: Mean entry lipids (mg/dL) were: TG 187, LDL-C 171, and HDL-C 39. Mean BMI was 32.6 Kg/m(2). Monotherapy with Slo-Niacin® decreased median triglyceride 15%, mean LDL-C 12% and non-HDL-C 15% and increased HDL-C 8%. Atorvastatin decreased median triglyceride 26%, and mean LDL-C 36%, non-HDL-C 36% and increased HDL-C 6%. Combined therapy decreased median triglyceride 33% and mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all p<0.001). Median remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median hsCRP 23% (all p<0.05), TNFa 12% and no change in IL-6. Mean LDL buoyancy increased 15%, apo-A-I 5% and median HDL(2)-C 20% (all p<0.05). ALT declined with Slo-Niacin® treatment alone compared to atorvastatin and also decreased when Slo-Niacin® was added to atorvastatin. Six subjects dropped out, 3 for niacin related symptoms. CONCLUSIONS: Slo-Niacin® 1.5g/day with atorvastatin 10 mg/day improved lipoprotein lipids, apoproteins and inflammation markers without hepatotoxicity. Slo-Niacin® deserves further study as a cost-effective treatment of hyperlipidemia.

Combined statin and niacin therapy remodels the high-density lipoprotein proteome.

BACKGROUND: Boosting low high-density lipoprotein (HDL) levels is a current strategy for preventing clinical events that result from cardiovascular disease. We previously showed that HDL(3) of subjects with coronary artery disease is enriched in apolipoprotein E and that the lipoprotein carries a distinct protein cargo. This observation suggests that altered protein composition might affect the antiatherogenic and antiinflammatory properties of HDL. We hypothesized that an intervention that increases HDL levels-combined statin and niacin therapy-might reverse these changes. METHODS AND RESULTS: HDL(3) isolated from 6 coronary artery disease subjects before and 1 year after combination therapy was analyzed by liquid chromatography-Fourier transform-mass spectrometry. Alterations in protein composition were detected by spectral counting and confirmed with extracted ion chromatograms. We found that combination therapy decreased the abundance of apolipoprotein E in HDL(3) while increasing the abundance of other macrophage proteins implicated in reverse cholesterol transport. Treatment-induced decreases in apolipoprotein E levels of HDL(3) were validated biochemically in a second group of 18 coronary artery disease subjects. Interestingly, the changes in HDL(3) proteome with niacin/statin treatment resulted in a protein composition that more closely resembled that of HDL(3) in healthy control subjects. CONCLUSIONS: Combined statin and niacin therapy partially reverses the changes in the protein composition seen in HDL(3) in coronary artery disease subjects. Our observations raise the possibility that quantifying the HDL proteome could provide insights into the therapeutic efficacy of antiatherosclerotic interventions.

Comprehensive lipid management versus aggressive low-density lipoprotein lowering to reduce cardiovascular risk.

Five lines of evidence justify comprehensive lipoprotein management over aggressive low-density lipoprotein (LDL) lowering alone in most cases of cardiovascular disease (CVD) prevention. First, lipoprotein lipid transport consists of a single, recycling system involving very-low-density lipoprotein, LDL, and high-density lipoprotein (HDL). Single lipid interventions affect all lipoprotein classes to varying degrees. These effects can be expanded by using different drug classes in combination. Second, observational studies support the unitary nature of lipoprotein risk. A family of curves describes increasing CVD risk from increasing LDL as other risk factors are present. Conversely, a family of curves describes increasing CVD risk from decreasing levels of HDL in mirror image to LDL. The LDL and HDL risks are additive. Third, clinical trials that raise HDL and lower triglyceride ameliorate CVD, as does lowering LDL. Lowering LDL prevents heart disease, but by only 22%-36% with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy. Studies indicate that better CVD prevention is obtained when drugs for triglyceride and HDL reduction are combined with LDL reduction. Fourth, HDL and its apolipoprotein (apo), apo A-I, as well as apo A-I analogues, decrease atherosclerosis. Each modality decreases atherosclerosis in animal models, and apo A-I Milano acutely decreases human coronary luminal stenosis. Apo A-I analogues have similar promise. Fifth, combined hyperlipidemia is the most common lipid disorder, has the strongest risk for CVD, and combines elevated LDL, hypertriglyceridemia, and low HDL. This condition requires the comprehensive treatment approach described above. In conclusion, 5 lines of evidence justify comprehensive diet and drug treatment for combined hyperlipidemia and, at lesser LDL elevations, the atherogenic dyslipidemias of obesity, diabetes mellitus, and the metabolic syndrome.

Survey correlations: proficiency and adequacy of nutrition training of medical students.

OBJECTIVE: The majority of graduating US medical students reported inadequate nutrition training over the past decade. This trend could in part be due to the lack of valid measures to assess the relationship between adequacy of nutrition training and proficiency on nutrition topics deemed essential. The study's objective was to test the hypothesis that self-reported nutrition proficiency is positively correlated with the perceived adequacy (quality, quantity, coverage and importance) of nutrition training of University of Washington medical students. METHOD: Cross-sectional e-mail survey of 1st to 4th year medical students (n = 708), including a survey prompt and three e-mail follow-up measures. To reduce and interpret the survey data, principal components analysis was employed, followed by Varimax rotation with Kaiser normalization. To assess internal consistency reliability, alpha (alpha) of nutrition proficiency items and factors was determined. RESULTS: A 44.5% response rate was achieved (n = 315 respondents). The 31-item questionnaire was reduced to 6 factors, explaining 60.2% of the total variance (alpha = 0.947). Self reported nutrition proficiency was positively correlated with the perceived quality, quantity and coverage of nutrition training in all 6 essential nutrition factors or topics determined after factor analysis (P < 0.01). CONCLUSION: Quality and coverage may be effective gauges of adequacy of nutrition training and related nutrition proficiency in medical education. Current national medical education evaluation measures focus on the quantity of nutrition instruction. The lowest reported proficiency topics; nutrition and disease management, micronutrients and complementary and alternative medicine are recommended for particular curricular emphasis.