Troy Madsen

Plasma Homocysteine Predicts Mortality Independently of Traditional Risk Factors and C-Reactive Protein in Patients With Angiographically Defined Coronary Artery Disease

BackgroundPlasma homocysteine (tHCY) has been associated with coronary artery disease (CAD). We tested whether tHCY also increases secondary risk, after initial CAD diagnosis, and whether it is independent of traditional risk factors, C-reactive protein (CRP), and methylenetetrahydrofolate reductase (MTHFR) genotype. Methods and ResultsBlood samples were collected from 1412 patients with severe angiographically defined CAD (stenosis ≥70%). Plasma tHCY was measured by fluorescence polarization immunoassay. The study cohort was evaluated for survival after a mean of 3.0±1.0 years of follow-up (minimum 1.5 years, maximum 5.0 years). The average age of the patients was 65±11 years, 77% were males, and 166 died during follow-up. Mortality was greater in patients with tHCY in tertile 3 than in tertiles 1 and 2 (mortality 15.7% versus 9.6%, P =0.001 [log-rank test], hazard ratio [HR] 1.63). The relative hazard increased 16% for each 5-&mgr;mol/L increase in tHCY (P <0.001). In multivariate Cox regression analysis, controlling for univariate clinical and laboratory predictors, elevated tHCY remained predictive of mortality (HR 1.64, P =0.009), together with age (HR 1.72 per 10-year increment, P <0.0001), ejection fraction (HR 0.84 per 10% increment, P =0.0001), diabetes (HR 1.98, P =0.001), CRP (HR 1.42 per tertile, P =0.004), and hyperlipidemia. Homozygosity for the MTHFR variant was weakly predictive of tHCY levels but not mortality. ConclusionsIn patients with angiographically defined CAD, tHCY is a significant predictor of mortality, independent of traditional risk factors, CRP, and MTHFR genotype. These findings increase interest in tHCY as a secondary risk marker and in secondary prevention trials (ie, with folate/B vitamins) to determine whether reduction in tHCY will reduce risk.

Cytomegalovirus Seropositivity and C-Reactive Protein Have Independent and Combined Predictive Value for Mortality in Patients With Angiographically Demonstrated Coronary Artery Disease

BackgroundThe role of inflammation in coronary artery disease (CAD) is being increasingly recognized. Markers of inflammation (eg, C-reactive protein [CRP]) and infection (eg, seropositivity to Chlamydia pneumoniae, cytomegalovirus [CMV], and Helicobacter pylori) have been proposed as risk factors for CAD, but these associations require further evaluation. Methods and ResultsWe prospectively tested whether CRP levels and IgG seropositivity to C pneumoniae, CMV, and H pylori are predictors of subsequent mortality in 985 consecutive patients with angiographically demonstrated CAD (stenosis ≥70%). Patients were followed for an average of 2.7 years (range 1.5 to 4.0 years). Patients averaged 65 years of age; 77% were men; and 110 (11.2%) died during follow-up. CRP levels were significantly elevated in nonsurvivors compared with survivors (mean CRP 3.1 mg/dL versus 1.5 mg/dL, P =0.003). After controlling for all known baseline variables, the 2nd and 3rd tertiles of CRP compared with the 1st produced a Cox hazard ratio (HR) for mortality of 2.4 (P =0.001). Of the 3 infectious markers tested, only seropositivity to CMV (HR=1.9, P <0.05) was predictive of mortality. The majority of mortality risk associated with elevated CRP or CMV seropositivity occurred when both risk factors were present (P for trend <0.0001). Other independent predictors of increased risk of mortality were age (HR=1.07 per year, P <0.0001), left ventricular ejection fraction (HR=0.97 per percent, P <0.0001), and diabetes mellitus (HR=1.7, P =0.02). ConclusionsCMV seropositivity and elevated CRP, especially when in combination, are strong, independent predictors of mortality in patients with CAD. This suggests an interesting hypothesis that a chronic, smoldering infection (CMV) might have the capacity to accelerate the atherothrombotic process.

Statin Therapy Interacts With Cytomegalovirus Seropositivity and High C-Reactive Protein in Reducing Mortality Among Patients With Angiographically Significant Coronary Disease

Background—Seropositivity to cytomegalovirus (CMV) and elevated C-reactive protein (CRP) may jointly predict increased mortality rates in patients with coronary artery disease (CAD). Therapy with statins reduces lipid levels but may also have other beneficial (eg, antiinflammatory) effects. This study prospectively evaluated the effect of statins on CMV-and CRP-associated death among patients with significant, angiographically defined CAD. Methods and Results—We monitored 2315 patients with angiographically significant CAD (stenosis ≥70%) for an average of 2.4 years (maximum, 5.8 years). Anti-CMV IgG antibody levels and CRP concentrations were measured at baseline, and statin prescription was recorded. As previously reported, mortality rate was higher for CMV seropositivity (+) with high CRP (hazard ratio [HR], 2.0) and lower for statins (HR, 0.50). Compared with CMV(−)/low CRP (mortality rate, 5% with statin versus 4% without statin), the protective effect of statin therapy was markedly greater for CMV(+)/low CRP (mortality rate, 2% versus 7%; HR, 0.44; 95% CI, 0.16 to 1.3), CMV negative (−)/high CRP (mortality rate, 1% versus 8%; HR, 0.16), and CMV(+)/high CRP (mortality rate, 6% versus 17%; HR, 0.42; 95% CI, 0.25 to 0.70). After adjustment, interactions were found for statin therapy with CMV(+)/low CRP (P for interaction=0.065), CMV(−)/high CRP (P for interaction=0.051), and CMV(+)/high CRP (P for interaction=0.024). Conclusions—The survival benefit of statins interacted with CMV seropositivity and high CRP to significantly reduce mortality rates among patients with CAD. This finding supports the hypothesis that statins have beneficial, “lipid-independent,” antiinflammatory effects. The mechanism of statin benefit associated with CMV seropositivity remains to be determined.

Efficacy of high-flow oxygen therapy in all types of headache: a prospective, randomized, placebo-controlled trial ☆

OBJECTIVE We aimed to assess the efficacy of oxygen inhalation therapy in emergency department (ED) patients presenting with all types of headache. METHOD We performed a prospective, randomized, double-blinded, placebo-controlled trial of patients presenting to the ED with a chief complaint of headache. The patients were randomized to receive either 100% oxygen via nonrebreather mask at 15 L/min or the placebo treatment of room air via nonrebreather mask for 15 minutes in total. We recorded pain scores at 0, 15, 30, and 60 minutes using the visual analog scale. At 30 minutes, the patients were assessed for the need for analgesic medication. Patient headache type was classified by the treating emergency physician using standardized diagnostic criteria. RESULTS A total of 204 patients agreed to participate in the study and were randomized to the oxygen (102 patients) and placebo (102 patients) groups. Patient headache types included tension (47%), migraine (27%), undifferentiated (25%), and cluster (1%). Patients who received oxygen therapy reported significant improvement in visual analog scale scores at all points when compared with placebo: 22 mm vs 11 mm at 15 minutes (P < .001), 29 mm vs 13 mm at 30 minutes (P < .001), and 55 mm vs 45 mm at 60 minutes (P < .001). When questioned at 30 minutes, 72% of patients in the oxygen group and 86% of patients in the placebo group requested analgesic medication (P = .005). CONCLUSION In addition to its role in the treatment of cluster headache, high-flow oxygen therapy may provide an effective treatment of all types of headaches in the ED setting.

Evaluation of mid-regional pro-atrial natriuretic peptide, procalcitonin, and mid-regional pro-adrenomedullin for the diagnosis and risk stratification of dyspneic ED patients☆☆☆★★★

OBJECTIVE The aim of this study was to evaluate the diagnostic and the prognostic value of a laboratory panel consisting of mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) for patients presenting to the emergency department (ED) with acute dyspnea. METHODS We prospectively enrolled ED patients who presented with a chief complaint of dyspnea and who had an uncertain diagnosis after physician evaluation. Final primary diagnosis of the cause of shortness of breath was confirmed through additional testing per physician discretion. We recorded inpatient admission and 30-day mortality rates. RESULTS One hundred fifty-four patients were enrolled in the study. Congestive heart failure exacerbation was the final primary diagnosis in 42.2% of patients, while infectious etiology was diagnosed in 33.1% of patients. For the diagnosis of congestive heart failure exacerbation, MR-proANP had a sensitivity of 92.7% and specificity of 36.8%, with a negative likelihood ratio (LR-) of 0.16 and a positive likelihood ratio (LR+) of 1.44 (cut-off value: 120 pmol/L). For the diagnosis of an infectious etiology, PCT had a 96.5% specificity and 48.8% sensitivity (LR-: 0.58, LR+: 13.8, cutoff value: 0.25 ng/mL). As a prognostic indicator, MR-proADM demonstrated similar values: odds ratio for 30-day mortality was 8.5 (95% CI, 2.5-28.5, cutoff value: 1.5 nmol/L) and the area under the receiver operating characteristic curve in predicting mortality was 0.81 (95% CI, 0.71-0.91). CONCLUSION The good negative LR- of MR-proANP and the good positive LR+ of PCT may suggest a role for these markers in the early diagnosis of ED patients with dyspnea. Furthermore, MR-proADM may assist in risk stratification and prognosis in these patients..

Utility of the Emergency Department Observation Unit in Ensuring Stress Testing in Low-Risk Chest Pain Patients

BACKGROUND Recent research has noted low rates of compliance among ED chest pain patients referred for outpatient stress testing. The practice at our institution, a 39,000 visits per year emergency department (ED), is to place chest pain patients considered low risk for acute coronary syndrome in an observation unit for serial biomarker testing and provocative cardiac testing. Our objective was to determine the rates of positive stress tests among this group and to extrapolate from this the potential missed positive stress tests if these patients were referred instead for outpatient stress testing. METHODS This was a retrospective chart review of all chest pain patients admitted to the ED observation unit between April 2006 and June 2007. Baseline information, including a history of coronary disease, was recorded. Patients underwent a treadmill stress test, nuclear stress test, or coronary CT scan at the discretion of the attending emergency physician and/or the consulting cardiologist. Rates of positive stress test or coronary CT and patient disposition (admission to an inpatient unit versus discharge for outpatient follow-up) were noted. RESULTS A total of 353 patients underwent stress testing or coronary CT during the study period: 257 (72.8%) patients had an exercise treadmill echocardiogram, 61 (17.3%) patients underwent nuclear stress testing, and 35 (9.9%) patients had a coronary CT. Seventy patients (19.8%) had a history of coronary disease but had been considered appropriate for observation by the attending emergency physician. Thirty-nine stress tests were positive (11%) and 11 were indeterminate (3.1%). Among patients with no history of coronary disease, 20 stress tests were positive (7.1%), and 10 were indeterminate (3.5%). Of all patients with a positive stress test, 19 (48.7%) underwent cardiac catheterization and 1 (2.6%) had coronary artery bypass graft. Twenty-one of 39 patients with a positive stress test (54%) were ultimately admitted to an inpatient unit per the recommendation of the consulting cardiologist. Assuming a best-case scenario in which 70% of patients referred for outpatient stress testing actually have the testing done (based on a recent report of outpatient compliance), physicians would miss approximately 3.3% of patients with a positive stress test if these patients were discharged directly from the ED. CONCLUSION Among chest pain patients admitted to an ED observation unit, the rate of positive stress tests was 11%. Approximately 3.3% of patients with positive stress tests may have been missed if these patients were instead referred for outpatient testing.

Geriatric Patients May Not Experience Increased Risk of Oligoanalgesia in the Emergency Department

STUDY OBJECTIVE The aim of this study is to compare the pain management practices in geriatric patients in the emergency department (ED) with that in other adult ED patients to determine whether these patients face increased risk of oligoanalgesia. METHODS This study was a prospective analysis of a convenience sample of patients presenting to an urban academic tertiary care hospital ED from 2000 through 2010. We compared patients aged 65 years and older (geriatric) with adults younger than 65 years and evaluated analgesic administration rates, opioid administration and dosing, and pain and satisfaction scores (0 to 10 scale). RESULTS A total of 15,387 patients presented to the ED during the 10-year study period and agreed to participate in the study; 1,169 patients were geriatric (7.6%). Geriatric patients had a mean age of 75.0 years (SD 7.2 years), whereas mean age of the 14,218 nongeriatric patients was 35.5 years (SD 12.2 years). Geriatric patients reported less pain at presentation (6.2 versus 6.9). After adjusting for presentation pain scores, geriatric patients were not less likely to receive an analgesic during the ED visit (odds ratio 0.90; 95% confidence interval 0.78 to 1.05) or less likely to receive an opioid (odds ratio 1.01; 95% confidence interval 0.87 to 1.18). Geriatric patients, on average, received lower doses of morphine (3.3 versus 4.2 mg) and had longer waiting times for their initial dose of an analgesic medication (65 versus 75 minutes). CONCLUSION Despite longer wait times for analgesia, geriatric and nongeriatric patients were similar in rates of analgesia and opioid administration for pain-related complaints. These findings contrast with previous studies reporting lower rates of analgesia administration among geriatric patients.

Intranasal sufentanil for the treatment of acute pain in a winter resort clinic

INTRODUCTION Painful extremity injuries are common patient complaints in resort clinics, urgent care clinics, and emergency departments. We hypothesized that intranasal (IN) sufentanil could provide rapid, noninvasive, effective pain relief to patients presenting with acute extremity injuries. METHODS This was an unblinded, nonrandomized, observational study that enrolled a convenience sample of patients presenting to a university-affiliated ski clinic with acute moderate to severe pain associated with a traumatic injury between the months of January and March 2011. Patients were excluded if they reported an allergy to sufentanil or had hypoxia, significant head injury, or hypotension. Nurses administered IN sufentanil using an IN atomizer device. The nurse recorded patient-reported pain scores (0-10 scale) on arrival and at 10, 20, and 30 minutes after administration of sufentanil. RESULTS During the study period, 40 patients were enrolled; 75% were men. The average age was 32 years (range, 16-60 years). The average dose of sufentanil was 37.7 μg. Five patients (12.5%) were given additional IN analgesia. Average pain on arrival was 9 (on a 10-point scale), and the mean reduction in pain scores was 4.7 (95% confidence interval [CI], 3.67-5.57) at 10 minutes, 5.79 (95% CI, 4.81-6.77) at 20 minutes, and 5.74 (95% CI, 4.72-6.76) at 30 minutes. CONCLUSION In this limited observational trial, IN sufentanil provided rapid, safe, and noninvasive pain relief to patients presenting with acute traumatic extremity injuries. Given the ease of administration, this may serve as a viable option for use in other settings, such as urgent care clinics and emergency departments.

Perceived confidence in the FAST exam before and after an educational intervention in a developing country.

BackgroundTrauma care in developing countries suffers from many limitations related to equipment shortages, disrepair, quality assurance, and lack of training. Health care providers in the three principal hospitals in Cusco, Peru have ultrasound machines, but they do not utilize this for the focused assessment of sonography in trauma (FAST) scan (only one of the three hospitals has a computed tomography scanner).AimsThe goal of this study was to assess the confidence of physicians in a developing country to conduct a FAST exam after an educational intervention.MethodsParticipants were Peruvian health care workers who attended a 2-day conference on trauma. Participants completed a questionnaire based on a 5-point Likert scale (1 = no confidence, 5 = high confidence) to assess comfort with the FAST scan before and after a FAST teaching workshop, which included hands-on ultrasound training. Thirteen individuals, eight of whom were physicians, completed the training and survey. Results were analyzed using paired t test statistics and are reported as pre- and post-training mean scores (± standard error), with p < 0.05 considered statistically significant.ResultsParticipants rated their confidence in using the FAST exam on a trauma patient with an average score of 3.3 (± 0.3) pre-training and 4.5 (± 0.2) post-training (p = 0.007). When asked about their comfort level in making clinical decisions based on the FAST scan, pre-training average score was 3.5 (± 0.4) and post-training was 4.5 (± 0.2), p = 0.016. Participants also answered questions about their comfort with the technical aspects of using the ultrasound machine: ability to choose the correct probe (pre: 3.9, post: 4.6, p = 0.011), choosing the correct probe orientation (pre: 3.9, post: 4.6, p = 0.008), and adjusting the depth and gain (pre: 3.1, post: 4.4, p = 0.001). Finally, participants rated their comfort with the specific views of the FAST scan: ability to find the correct subcostal view (pre: 3.3, post: 4.9, p < 0.001), right upper quadrant view (pre: 3.2, post: 4.6, p < 0.001), left upper quadrant view (pre: 3.2, post: 4.4, p = 0.001), and the pelvic view (pre: 3.2, post: 4.5, p < 0.001).ConclusionAfter a training session in the use of ultrasound in trauma, health care workers in Cusco, Peru reported increased confidence in their FAST scan ability and in their comfort in using this exam for clinical decision-making. Future research should include objective testing of participants’ skill as well as longitudinal follow-up to determine the extent to which the FAST scan has been incorporated into participants’ evaluations of trauma patients.

Low-risk young adult patients with chest pain may not benefit from routine cardiac stress testing: a Bayesian analysis.

INTRODUCTION Low-risk emergency department (ED) chest pain patients with a nondiagnostic electrocardiogram (ECG) and negative cardiac biomarkers are commonly evaluated with cardiac stress testing to detect undiagnosed coronary artery disease. Provocative testing incurs certain costs and may require additional time investment either in the ED or in an observation setting. Recent research has questioned the utility of provocative testing in young adults with negative cardiac biomarkers and nondiagnostic ECG. We sought to evaluate the utility of cardiac stress testing in our population of young adult patients with chest pain. METHODS We performed a retrospective chart review of all chest pain patients aged 40 years and younger who were admitted to our ED observation unit over the 14-month period between April 2006 and May 2007. We included all patients who were admitted to the observation unit for serial biomarkers and provocative testing and had normal or nondiagnostic ECG, no history of coronary disease, and an initial negative troponin. We recorded baseline characteristics and stress test results of these patients and reviewed the patient charts for the 30-day period following discharge to identify repeat hospital visits and adverse events. We used Bayesian analysis to estimate the rate of true-positive stress testing in this population, using the only prior study of unit patients showing as high as 2 of 220 patients testing positive as a prior estimate. RESULTS A total of 36 patients met inclusion criteria; average age was 34.6 years old (range: 22-40 years) and 61% were male. Patient risk factors included hypertension (19%), diabetes (6%), family history (42%), and smoking (44%). All patients had negative serial cardiac biomarkers and a negative treadmill stress echocardiogram. Thirty-day follow-up demonstrated no adverse cardiac events. We performed Bayesian analysis through the addition of the 36 patients to the 220 patients represented by prior data. The posterior probability distribution changed slightly in location and scale gave a median estimated rate of positive stress testing in this population of 1.04% (95% credible interval, 0.24%-2.78%). CONCLUSIONS The population of chest pain patients younger than 40 years with no history of coronary disease, a nondiagnostic ECG, and negative serial biomarkers may not benefit from provocative testing. Our findings complement those reported previously on the limited utility of cardiac stress testing in this population.