The Flipped Classroom in Emergency Medicine Using Online Videos with Interpolated Questions.

BACKGROUND: Utilizing the flipped classroom is an opportunity for a more engaged classroom session. This educational approach is theorized to improve learner engagement and retention and allows for more complex learning during class. No studies to date have been conducted in the postgraduate medical education setting investigating the effects of interactive, interpolated questions in preclassroom online video material. OBJECTIVES: We created a flipped classroom for core pediatric emergency medicine (PEM) topics using recorded online video lectures for preclassroom material and interactive simulations for the in-classroom session. METHODS: Lectures were filmed and edited to include integrated questions on an online platform called Zaption. One-half of the residents viewed the lectures uninterrupted (Group A) and the remainder (Group B) viewed with integrated questions (2-6 per 5-15-min segment). Residents were expected to view the lectures prior to in-class time (total viewing time of approximately 2½ h). The 2½-h in-class session included four simulation and three procedure stations, with six PEM faculty available for higher-level management discussion throughout the stations. Total educational time of home preparation and in-class time was approximately 5 h. RESULTS: Residents performed better on the posttest as compared to the pretest, and their satisfaction was high with this educational innovation. In 2014, performance on the posttest between the two groups was similar. However, in 2015, the group with integrated questions performed better on the posttest. CONCLUSION: An online format combined with face-to-face interaction is an effective educational model for teaching core PEM topics.

Does Right Lower Quadrant Abdominal Ultrasound Accurately Identify Perforation in Pediatric Acute Appendicitis?

BACKGROUND: Acute appendicitis is the most common cause of acute abdomen in pediatric emergency department (ED) visits, and right lower quadrant abdominal ultrasound (RLQUS) is a valuable diagnostic tool in the clinical approach. The utility of ultrasound in predicting perforation has not been well-defined. OBJECTIVES: We sought to determine the sensitivity of RLQUS to identify perforation in pediatric patients with appendicitis. METHODS: A chart review of all patients 3 to 21 years of age who received a radiographic work-up and who were ultimately diagnosed with perforated appendicitis between 2010 and 2013 at a pediatric ED was conducted. The final read for ultrasonography was compared to either the operative diagnosis, surgical pathology diagnosis, or further imaging results (if the patient was managed nonoperatively). Test characteristics were calculated for the identification of appendicitis and identification of perforation. RESULTS: Of the 539 patients evaluated for appendicitis, 144 (26.7%) patients had appendicitis, and 40 of these (27.8%) were perforated. Thirty-nine had RLQUS performed as part of their evaluation. Of these, 28 had positive findings for appendicitis, and 9 were read as definite or possible perforated appendicitis. The sensitivity of RLQUS for the diagnosis of appendicitis in the group with perforation was 77.1% (95% confidence interval [CI], 59.4-89%) and the sensitivity for diagnosing a perforation was 23.1% (95% CI, 11.1-39.3%). CONCLUSION: There was a low rate of detection of perforation by RLQUS in our pediatric population. If larger studies confirm this, additional imaging should be recommended in patients with a high suspicion of perforation and in whom a diagnosis of perforation would change management.

Inflammation and future risk of symptomatic heart failure in patients with stable coronary artery disease.

BACKGROUND: Heart failure (HF) carries poor prognosis in coronary artery disease (CAD) patients despite advances in therapy. Inflammation predicts recurrent cardiovascular events in CAD patients. It is unknown whether increased levels of inflammatory markers are associated with incident HF in these patients. AIM: The aims of this study were to evaluate the association between inflammatory markers and future HF risk in patients with stable CAD and to explore possible mediation by myocardial infarction (MI). METHODS: The study comprised 2,945 patients with stable CAD without HF at baseline during a median follow-up of 7.9 years. Inflammatory baseline markers were the basis of this study. RESULTS: Heart failure was diagnosed in 508 patients (17.2%). Patients who developed HF were older and had more often previous MI, diabetes, hypertension, and peripheral vascular disease. Baseline levels of C-reactive protein (CRP), fibrinogen, and white blood cells (WBCs) were significantly higher in patients who developed HF compared with those who did not. Age-adjusted incident HF rates were related to elevated baseline inflammatory markers in a dose-response manner. Adjusting for multiple confounders, the HF hazard ratios were 1.38 (95% CI 1.11-1.72), 1.33 (95% CI 1.07-1.66), and 1.36 (95% CI 1.10-1.68) for the third tertiles of CRP, fibrinogen, and WBC levels, respectively. Hazard ratio for the fifth quintile of a combined "inflammation score" was 1.83 (95% CI 1.40-2.39). Mediation by MI preceding the HF onset during follow-up accounted for 10.4%, 10.8%, and 8.6% of the association of subsequent HF with CRP, fibrinogen, and WBC, respectively. CONCLUSIONS: Increased levels of CRP, fibrinogen, and WBC are independently related to the incidence of HF in patients with stable CAD.

Primary angioplasty in patients following coronary artery bypass surgery: trends in application and outcome. Results from the acute coronary syndrome Israeli Survey (ACSIS) 2000-2008.

OBJECTIVES: We aimed to study the trends in management and outcome of post CABG patients presenting with acute MI. BACKGROUND: Primary angioplasty is the treatment of choice in patients with acute myocardial infarction. Saphenous vein grafts used for CABG are large-diameter conduits that tend to accumulate a large mass of thrombus when they are the culprit artery for acute myocardial infarction (MI). We hypothesized that performing PCI in these patients is more complex and possibly results in worse outcome compared to non-CABG patients. METHODS: Data for patients with STEMI was obtained from five acute coronary syndromes Israeli biennial Surveys (ACSIS) during 2000-2008. Baseline characteristics, management and outcome of post-CABG patients were compared to non-post CABG patients during 2006-2008 surveys. RESULTS: A total of 9,781 patients were included. About 1,002 (10.2%) were post-CABG. Reperfusion therapy for post-CABG patients (34-48%) was consistently lower compared to non-CABG patients (57-65%). Angiographic outcome in patients with STEMI who underwent primary PCI (17 post-CABG, mean age 66.6 ± 9.1 and 821 non-CABG, age 60.1 ± 12.9) was successful (TIMI flow 3) in 86 and 88%, respectively. Thirty-day mortality was 5.9 and 5.1% (P = 0.89) and MACE rates were 17.6 and 12.5%, respectively (P = 0.54). CONCLUSIONS: Use of primary PCI in post-CABG patients was lower than in non-CABG patients but increased steadily and to a similar extent in both groups. Angiographic and clinical outcome was similar despite assumingly larger thrombus burden in post CABG patients. Therefore, primary angioplasty is appropriate also in post-CABG patients presenting with STEMI.

Bypassing the emergency room to reduce door-to-balloon time and improve outcomes of patients with ST elevation myocardial infarction: the Acute Coronary Syndrome Israeli Survey experience.

BACKGROUND: Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time. OBJECTIVES: To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients' clinical outcome. METHODS: We analyzed data of 776 patients with STEMI from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups. RESULTS: There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P< 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P= 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE was significantly lower in the direct ICCU group (22 vs. 30%, P< 0.004). CONCLUSIONS: There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.

Technology-Dependent Children.

There are a growing number of medically complex children with implanted devices. Emergency physicians with a basic knowledge of these devices can troubleshoot and fix many of the issues that may arise. Recognition of malfunction of these devices can reduce morbidity and mortality among this special population. In this article, we review common issues that may arise in children with gastrostomy tubes, central nervous system shunts, cochlear implants, and vagal nerve stimulators.

Combination of the Killip and TIMI classifications for early risk stratification of patients with acute ST elevation myocardial infarction.

OBJECTIVE: The Killip classification and the Thrombolysis in Myocardial Infarction (TIMI) score have been proven to be useful tools for the early risk stratification of patients with acute myocardial infarction (MI). The Killip classification is simpler and less time consuming compared to the TIMI score. We sought to evaluate the added value of applying the TIMI score to patients prestratified with the Killip classification. METHODS: A total of 1,773 consecutive acute MI patients were hospitalized in 25 coronary care units operating in Israel, and were followed up to 1 year. RESULTS: Higher Killip class was associated with increased 1-year mortality: 6, 24, 42 and 60% in Killip 1-4, respectively. Applying the TIMI score to Killip 1 patients resulted in further stratifying the patients to low-, medium- and high-risk patient groups with 1, 8 and 19% 1-year mortality rates. CONCLUSIONS: The Killip classification is a useful tool for early risk stratification of acute MI patients. Applying the TIMI score to patients classified as Killip 1 further stratified them into low-, medium- and high-risk subgroups significantly improving stratification by the Killip classification alone.

Blood transfusion for acute decompensated heart failure--friend or foe?

BACKGROUND: In acute coronary syndromes (ACSs), blood transfusion (BT) has been associated with worse outcomes. The impact of BT among patients with acute decompensated heart failure (ADHF) remains unknown. METHODS: Propensity score analysis of patients with ADHF with and without BT in a national heart failure (HF) survey was used in this study. RESULTS: Of the 4,102 enrolled patients, 2,335 had ADHF, of whom 166 (7.1%) received BT. These patients were older (75.6% vs 73.6%, P = .04), more likely to be females (54.8% vs 43.9%, P = .007), more likely to have diabetes (59.0% vs 51.1%, P = .04) and renal dysfunction (59.0% vs 40.2%, P < .001), and more likely to receive inotropes (16.9% vs 8.0%, P < .001), but they had similar rates of ACS (41.0% vs 39.4%, P = .69) and prior HF (64.5% vs 70.0%, P = .23). Nadir hemoglobin levels were commonly <10 g/dL in BT patients (92.7% vs 8.0%); 15 BT patients had bleeding complications, of which 10 are major bleeding. Major predictors for BT were ACS (OR 1.85, 95% CI 1.15-2.96), inotropes use (OR 2.36, 95% CI 1.22-4.55), and nadir hemoglobin (OR 0.18 per 1 g/dL increase, 95% CI 0.14-0.22). In-hospital, 30-day, 1-year, and 4-year unadjusted mortality rates were higher for BT patients (10.8% vs 5.2%, P = .02; 11.0% vs 8.5%, P = .27; 39.6% vs 28.5%, P = .03; 69.5% vs 59.5%, P = .01, respectively). However, in 103 propensity-matched pairs (c-statistic 0.97), short-term mortality tended to be lower with BT (8.7% vs 14.6%, P = .20; 9.7% vs 18.4%, P = .08; 38.8% vs 42.7%, P = .59; and 72.8% vs 76.7%, P = .52, respectively). CONCLUSIONS: Acute decompensated HF patients receiving BT had worse clinical features and unadjusted outcomes, but BT per se seemed to be safe and perhaps even beneficial.

Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment.

BACKGROUND: The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. RESULTS: During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). CONCLUSION: Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.

Effect of bundle branch block patterns on mortality in hospitalized patients with heart failure.

A widened QRS interval is associated with increased mortality in patients with heart failure (HF). However, the prognostic significance of the type of bundle branch block (BBB) pattern in these patients is unclear. The data of 4,102 patients with HF hospitalized during a prospective national survey were analyzed to investigate the association between BBB type and 1-year mortality in 3,737 patients without pacemakers. Right BBB (RBBB) was present in 381 patients (10.2%) and left BBB (LBBB) in 504 patients (13.5%). RBBB and LBBB were associated with increased 1-year mortality on univariate analysis (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.15 to 1.81, and OR 1.20, 95% CI 0.97 to 1.47, respectively). In patients with systolic HF, after adjusting for multiple risk factors, only RBBB was found to be an independent predictor of mortality (RBBB vs no BBB OR 1.62, 95% CI 1.12 to 2.33, and RBBB vs LBBB OR 1.71, 95% CI 1.09 to 2.69). This correlation was stronger in patients with lower left ventricular ejection fractions and was also maintained in patients without acute myocardial infarctions. Analyzing the data for all patients with HF, there was a trend for increased mortality in the RBBB group only (adjusted OR 1.21, 95% CI 0.94 to 1.56). LBBB was not related to mortality in patients with either systolic HF or preserved ejection fractions. In conclusion, RBBB rather than LBBB is an independent predictor of mortality in hospitalized patients with systolic HF. This prognostic marker could be used for risk stratification and the selection of treatment.

Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease?

BACKGROUND: Epidemiologic studies have suggested that hypertriglyceridemia and insulin resistance are related to the development of colon cancer. Nuclear peroxisome proliferator-activated receptors (PPAR), which play a central role in lipid and glucose metabolism, had been hypothesized as being involved in colon cancerogenesis. In animal studies the lipid-lowering PPAR ligand bezafibrate suppressed colonic tumors. However, the effect of bezafibrate on colon cancer development in humans is unknown. Therefore, we proposed to investigate a possible preventive effect of bezafibrate on the development of colon cancer in patients with coronary artery disease during a 6-year follow-up. METHODS: Our population included 3011 patients without any cancer diagnosis who were enrolled in the randomized, double blind Bezafibrate Infarction Prevention (BIP) Study. The patients received either 400 mg of bezafibrate retard (1506 patients) or placebo (1505 patients) once a day. Cancer incidence data were obtained by matching a subject's identification numbers with the National Cancer Registry. Each matched record was checked for correct identification. RESULTS: Development of new cancer (all types) was recorded in 177 patients: in 79 (5.25%) patients from the bezafibrate group vs. 98 (6.51%) from the placebo group. Development of colon cancer was recorded in 25 patients: in 8 (0.53%) patients from the bezafibrate group vs. 17 (1.13%) from the placebo group, (Fisher's exact test: one side p = 0.05; two side p = 0.07). A difference in the incidence of cancer was only detectable after a 4 year lag and progressively increased with continued follow-up. On multivariable analysis the colon cancer risk in patients who received bezafibrate tended to be lower with a hazard ratio of 0.47 and 95% confidence interval 0.2-1.1. CONCLUSION: Our data, derived from patients with coronary artery disease, support the hypothesis regarding a possible preventive effect of bezafibrate on the development of colon cancer.

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Disaster drill exercise documentation and management: are we drilling to standard?

INTRODUCTION: Medical errors are known to occur even in a controlled setting with adequate resources. The few studies on mass-casualty events and disaster exercises suggest errors may be amplified in these situations. We hypothesized that both the documentation and medical care provided during a pediatric disaster drill would be substandard when compared with routine care at the same institution. METHODS: Charts from the disaster exercise and matched charts from actual admitted patients were retrospectively reviewed for the presence of triage classification, allergies, weight, physical exam, vital signs, diagnosis, disposition time, disposition location, disposition instructions, and disposition vitals signs and for the appropriateness of diagnoses, medications, procedures, and disposition. Errors were quantified and classified into negligible, likely to cause temporary harm, or potential to cause admission or permanent harm. The drill charts were compared to actual charts by Fischer's Exact Test. RESULTS: Drill charts contained a significantly greater proportion of errors in regards to performance of procedures, administration of medication, and accuracy of diagnosis. Sixteen percent of these errors were judged as having the potential to cause permanent harm or admission. The exercise charts contained a significantly greater number of omissions in documentation in 9 of the 10 areas evaluated. DISCUSSION: Both the documentation and the quality of care provided during our exercise were deficient when compared with conventional care. Opportunities allowing providers to clearly document pertinent information, and linking of this documentation to relevant prompts and algorithms may minimize this potential for error.

Impact of metabolic syndrome in patients with acute coronary syndrome.

The reported incidence of metabolic syndrome among patients with an acute coronary syndrome varies between 29 and 46%. The standard fasting cut-off levels for glucose and blood pressure cannot be applied on admission in patients with acute coronary syndrome and therefore modified criteria were used to define the metabolic syndrome. Patients with metabolic syndrome and acute coronary syndrome had increased incidence of heart failure, and worse long-term mortality compared to those without metabolic syndrome. However, they had less heart failure than those with known diabetes mellitus. Hyperglycemia as a risk factor for poor outcome is particularly significant in patients with metabolic syndrome. De novo identification of the metabolic syndrome on admission has the potential to improve risk stratification and management of patients with an acute coronary syndrome.

Flipping the Classroom in Medical Student Education: Does Priming Work?

INTRODUCTION: The emergency medicine (EM) clerkship curriculum at Los Angeles County + University of Southern California Medical Center includes monthly lectures on pediatric fever and shortness of breath (SOB). This educational innovation evaluated if learning could be enhanced by "priming" the students with educational online videos prior to an in-class session. Factors that impacted completion rates were also evaluated (planned specialty and time given for video viewing). METHODS: Twenty-minute videos were to be viewed prior to the didactic session. Students were assigned to either the fever or SOB group and received links to those respective videos. All participating students took a pre-test prior to viewing the online lectures. For analysis, test scores were placed into concordant groups (test results on fever questions in the group assigned the fever video and test results on SOB questions in the group assigned the SOB video) and discordant groups (crossover between video assigned and topic tested). Each subject contributed one set of concordant results and one set of discordant results. Descriptive statistics were performed with the Mann-Whitney U test. Lecture links were distributed to students two weeks prior to the in-class session for seven months and three days prior to the in-class session for eight months (in which both groups included both EM-bound and non-EM bound students). RESULTS: In the fifteen-month study period, 64% of students rotating through the EM elective prepared for the in class session by watching the videos. During ten months where exclusively EM-bound students were rotating (n=144), 71.5% of students viewed the lectures. In four months where students were not EM-bound (n=54), 55.6% of students viewed the lectures (p=0.033). Participation was 60.2% when lecture links were given three days in advance and 68.7% when links were given two weeks in advance (p=0.197). In the analysis of concordant scores, the pre-test averaged 56.7% correct, the immediate post-test averaged 78.1% correct, and the delayed post-test was 67.2%. In the discordant groups, the pretest averaged 51.9%, the immediate posttest was 67.1% and the delayed by 68.8%. In the concordant groups, the immediate post-test scores improved by 21.4%, compared with 15.2% in the discordant groups (p = 0.655). In the delayed post-test the concordant scores improved by 10.5% and discordant scores by 16.9 percent (p=0.609). Sixty-two percent of students surveyed preferred the format of online videos with in-class case discussion to a traditional lecture format. CONCLUSION: Immediate post-tests and delayed post-tests improved but priming was not demonstrated to be a statistically superior educational method in this study. Medical student completion of the preparatory materials for the EM rotation session increased when the students were EM-bound. Participation rates were not significantly different when given at two weeks versus three days.

Pediatric Online Disaster Preparedness Training for Medical and Non-Medical Personnel: A Multi-Level Modeling Analysis.

IntroductionTerrorism and natural catastrophes have made disaster preparedness a critical issue. Despite the documented vulnerabilities of children during and following disasters, gaps remain in health care systems regarding pediatric disaster preparedness. This research study examined changes in knowledge acquisition of pediatric disaster preparedness among medical and non-medical personnel at a children's hospital who completed an online training course of five modules: planning, triage, age-specific care, disaster management, and hospital emergency code response. METHODS: A multi-disciplinary team within the Pediatric Disaster Resource and Training Center at Children's Hospital Los Angeles (Los Angeles, California USA) developed an online training course. Available archival course data from July 2009 to August 2012 were analyzed through linear growth curve multi-level modeling, with module total score as the outcome (0 to 100 points), attempt as the Level 1 variable (any module could be repeated), role in the hospital (medical or non-medical) as the Level 2 variable, and attempt by role as the cross-level effect. RESULTS: A total of 44,115 module attempts by 5,773 course participants (3,686 medical personnel and 2,087 non-medical personnel) were analyzed. The average module total score upon first attempt across all participants ranged from 60.28 to 80.11 points, and participants significantly varied in how they initially scored. On average in the planning, triage, and age-specific care modules: total scores significantly increased per attempt across all participants (average rate of change ranged from 0.59 to 1.84 points) and medical personnel had higher total scores initially and through additional attempts (average difference ranged from 13.25 to 16.24 points). Cross-level effects were significant in the disaster management and hospital emergency code response modules: on average, total scores were initially lower among non-medical personnel compared to medical personnel, but non-medical personnel increased their total scores per attempt by 3.77 points in the disaster management module and 6.40 points in the hospital emergency code response module, while medical personnel did not improve their total scores through additional attempts. CONCLUSION: Medical and non-medical hospital personnel alike can acquire knowledge of pediatric disaster preparedness. Key content can be reinforced or improved through successive training in an online course. PhamPK, BeharSM, BergBM, UppermanJS, NagerAL. Pediatric online disaster preparedness training for medical and non-medical personnel: a multi-level modeling analysis Prehosp Disaster Med. 2018;33(4):349-354.

C-reactive protein, bezafibrate, and recurrent coronary events in patients with chronic coronary heart disease.

BACKGROUND: Elevated C-reactive protein (CRP) levels are related to increased coronary risk in healthy subjects and in patients with acute coronary syndromes. The aims of the present study were to assess the following: (1) the association between CRP and subsequent coronary risk in patients with chronic coronary heart disease (CHD), (2) the effect of long-term bezafibrate treatment on CRP levels, and (3) to evaluate the consequences of change in CRP level over time on subsequent risk. METHODS: Patients with chronic CHD (n = 3122) were recruited to a secondary prevention study that assessed the efficacy of bezafibrate versus placebo. C-reactive protein was measured in plasma samples collected at prerandomization and after 2 years of follow-up. Mean follow-up time was 6.2 years. Primary end point was fatal and nonfatal myocardial infarction and sudden cardiac death. RESULTS: Increased baseline CRP levels were associated with increased risk (hazard ratios [HRs] per unit of log-transformed CRP level change) of myocardial infarction (HR 1.17, 95% CI 1.03-1.33), the primary end point (HR 1.19, 95% CI 1.06-1.34), total death (HR 1.19, 95% CI 1.02-1.40) and cardiac death (HR 1.28, 95% CI 1.04-1.59). After 2 years, CRP levels increased by 3.0% (from a mean level of 3.44 mg/L) in the bezafibrate group and by 3.7% (from 3.49 mg/L) in the placebo group. C-reactive protein levels after 2 years were associated with increased subsequent cardiovascular risk. CONCLUSIONS: Baseline CRP and 2-year CRP levels were associated with subsequent risk of myocardial infarction and death in patients with chronic CHD. Bezafibrate did not reduce CRP levels as compared with placebo.

Insulin resistance is associated with increased risk of major cardiovascular events in patients with preexisting coronary artery disease.

BACKGROUND: Over the past years it has been recognized that insulin resistance (IR) is an independent risk factor for the development of diabetes, whereas its association with cardiovascular events remains controversial. The aim of our study was to explore the association between IR per se and cardiovascular events among patients with preexisting coronary artery disease. METHODS: The mean follow-up period of this prospective study was 6.2 years. Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained at baseline from 2938 patients aged 45 to 74 years. The homeostatic index of IR (HOMA-IR) was calculated according to the homeostasis model assessment. RESULTS: New major cardiovascular events (fatal and nonfatal myocardial infarction and sudden death) were recorded in 108 (11.1%) patients from the lowest IR tertile, in 147 (14.7%) from the intermediate tertile, and in 166 (17.2%) from the highest tertile (P = .0002). The linear trend for total and cardiac death across the tertiles of HOMA-IR was significant as well (P = .02 and P = .009, respectively). The highest age-adjusted rates for major cardiovascular events and new diabetes were found among patients within the top tertile of HOMA-IR (57% and 130% higher rates, respectively, tertile 3 vs tertile 1, P < .0001 for both). Multivariable analysis identified HOMA-IR (tertile 3 vs tertile 1) as an independent predictor of increased risk of major cardiovascular events and new diabetes with hazard ratios (95% CI) of 1.4 (1.1-1.8) and 1.5 (1.1-2.0), respectively. CONCLUSIONS: Insulin resistance per se is an independent risk factor for cardiovascular events and new diabetes in patients with preexisting coronary artery disease.

Impact of the metabolic syndrome on the clinical outcomes of non-clinically diagnosed diabetic patients with acute coronary syndrome.

The aim of this study is to explore the impact of metabolic syndrome (MS) on the outcome of patients with non-clinically diagnosed diabetes with acute coronary syndrome (ACS) based on a comprehensive nationwide registry during a 1-year follow-up. In the ACS Israeli Survey, 1,060 consecutive patients with non-clinically diagnosed diabetes were admitted due to ACS; 359 patients with MS features on admission were compared with 701 subjects without MS. A modified National Cholesterol Education Program Adult Treatment Panel III definition of MS was used in patients who presented with > or =3 of the 5 components: (1) hyperglycemia, defined as occasional blood glucose on admission >140 mg/dl; (2) preexisting hypertension; (3) body mass index >28 kg/m(2); (4) high-density lipoprotein cholesterol < or =40 mg/dl (men) or < or =50 mg/dl (women); and (5) triglycerides > or =150 mg/dl. Patients with MS were more frequently women (27% vs 12%, p = 0.001), were in Killip > or =II on admission (19% vs 14%, p = 0.03), and had higher 30-day (5.0% vs 1.7%, p = 0.002) and 1-year (8.9% vs 4.6%, p = 0.005) crude mortality rates. Patients with hyperglycemia (glucose >140 mg/dl) and MS had higher 30-day mortality rates compared with patients with hyperglycemia without MS (8.3% vs 2.5%, p <0.05). Multivariate analysis identified MS as a strong independent predictor of 30-day and 1-year mortality with hazard ratios of 2.54 (95% confidence interval 1.22 to 5.31) and 1.96 (95% confidence interval 1.18 to 3.24), respectively. In conclusion, MS defined early at admission is a strong independent predictor of mortality and morbidity in patients with non-clinically diagnosed diabetes with ACS.