Monday, August 27, 2012

Lit Bits: Aug 27, 2012

From the recent medical literature... 

1. Inappropriateness of Medication Prescriptions to Elderly Patients in the Primary Care Setting: A Systematic Review 

Opondo D, et al. PLoS ONE 2012;7(8): e43617 

Background: Inappropriate medication prescription is a common cause of preventable adverse drug events among elderly persons in the primary care setting. 

Objective: The aim of this systematic review is to quantify the extent of inappropriate prescription to elderly persons in the primary care setting. 

Methods: We systematically searched Ovid-Medline and Ovid-EMBASE from 1950 and 1980 respectively to March 2012. Two independent reviewers screened and selected primary studies published in English that measured (in)appropriate medication prescription among elderly persons (over 65 years) in the primary care setting. We extracted data sources, instruments for assessing medication prescription appropriateness, and the rate of inappropriate medication prescriptions. We grouped the reported individual medications according to the Anatomical Therapeutic and Chemical (ATC) classification and compared the median rate of inappropriate medication prescription and its range within each therapeutic class. 

Results: We included 19 studies, 14 of which used the Beers criteria as the instrument for assessing appropriateness of prescriptions. The median rate of inappropriate medication prescriptions (IMP) was 20.5% [IQR 18.1 to 25.6%.]. Medications with largest median rate of inappropriate medication prescriptions were propoxyphene 4.52(0.10–23.30)%, doxazosin 3.96 (0.32 15.70)%, diphenhydramine 3.30(0.02–4.40)% and amitriptiline 3.20 (0.05–20.5)% in a decreasing order of IMP rate. Available studies described unequal sets of medications and different measurement tools to estimate the overall prevalence of inappropriate prescription.

Conclusions: Approximately one in five prescriptions to elderly persons in primary care is inappropropriate despite the attention that has been directed to quality of prescription. Diphenhydramine and amitriptiline are the most common inappropriately prescribed medications with high risk adverse events while propoxyphene and doxazoxin are the most commonly prescribed medications with low risk adverse events. These medications are good candidates for being targeted for improvement e.g. by computerized clinical decision support. 

2. Clinical features, management, and prognosis of spontaneous coronary artery dissection. 

Tweet MS, et al. Circulation. 2012 Jul 31;126(5):579-88.  

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized. 

METHODS AND RESULTS: A retrospective single-center cohort study identified 87 patients with angiographically confirmed SCAD. Incidence, clinical characteristics, treatment modalities, in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were evaluated. Mean age was 42.6 years; 82% were female. Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of 71; P less than 0.001), and postpartum status was observed in 13 of 71 women (18%). Presentation was ST-elevation myocardial infarction in 49%. Multivessel SCAD was found in 23%. Initial conservative management (31 of 87) and coronary artery bypass grafting (7 of 87) were associated with an uncomplicated in-hospital course, whereas percutaneous coronary intervention was complicated by technical failure in 15 of 43 patients (35%) and 1 death. During a median follow-up of 47 months (interquartile range, 18-106 months), SCAD recurred in 15 patients, all female. Estimated 10-year rate of major adverse cardiac events (death, heart failure, myocardial infarction, and SCAD recurrence) was 47%. Fibromuscular dysplasia of the iliac artery was identified incidentally in 8 of 16 femoral angiograms (50%) undertaken before closure device placement and in the carotid arteries of 2 others with carotid dissection. 

CONCLUSIONS: SCAD affects a young, predominantly female population, frequently presenting as ST-elevation myocardial infarction. Although in-hospital mortality is low regardless of initial treatment, percutaneous coronary intervention is associated with high rates of complication. Risks of SCAD recurrence and major adverse cardiac events in the long term emphasize the need for close follow-up. Fibromuscular dysplasia is a novel association and potentially causative factor. 

3. One-Hour Rule-out and Rule-in of AMI Using High-Sensitivity Cardiac Troponin T  

Reichlin T, et al. Arch Intern Med. Published online August 13, 2012. doi:10.1001/archinternmed.2012.3698  

Background  High-sensitivity cardiac troponin (hs-cTn) assays seem to improve the early diagnosis of acute myocardial infarction (AMI), but it is unknown how to best use them in clinical practice. Our objective was to develop and validate an algorithm for rapid rule-out and rule-in of AMI. 

Methods  A prospective multicenter study enrolling 872 unselected patients with acute chest pain presenting to the emergency department. High-sensitivity cardiac troponin T (hs-cTnT) was measured in a blinded fashion at presentation and after 1 hour. The final diagnosis was adjudicated by 2 independent cardiologists. An hs-cTnT algorithm incorporating baseline values as well as absolute changes within the first hour was derived from 436 randomly selected patients and validated in the remaining 436 patients. The primary prognostic end point was death during 30 days of follow-up. 

Results  Acute myocardial infarction was the final diagnosis in 17% of patients. After applying the hs-cTnT algorithm developed in the derivation cohort to the validation cohort, 259 patients (60%) could be classified as “rule-out,” 76 patients (17%) as “rule-in,” and 101 patients (23%) as in the “observational zone” within 1 hour. Overall, this resulted in a sensitivity and negative predictive value of 100% for rule-out, a specificity and positive predictive value of 97% and 84%, respectively, for rule-in, and a prevalence of AMI of 8% in the observational zone group. Cumulative 30-day survival was 99.8%, 98.6%, and 95.3% (P less than .001) in patients classified as rule-out, observational zone, and rule-in, respectively. 

Conclusions  Using a simple algorithm incorporating hs-cTnT baseline values and absolute changes within the first hour allowed a safe rule-out as well as an accurate rule-in of AMI within 1 hour in 77% of unselected patients with acute chest pain. This novel strategy may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients.

Here are the criteria they used for ruling out AMI: baseline hs-cTnT level under 12 ng/L and an absolute change within the first hour less than 3 ng/L 

And for ruling in AMI: baseline hs-cTnT of ≥52 ng/L or an absolute change in biomarker levels within the first hour of ≥5 ng/L. 

4. ESC: New Definition of MI Unveiled 

By Chris Kaiser, Cardiology Editor, MedPage Today. August 25, 2012. MUNICH -- An international, multispecialty task force has published a new definition of myocardial infarction that was prompted by the new generation of highly sensitive cardiac troponin (cTn) assays. 

The highly sensitive assays are capable of detecting cTn in conditions other than MI, such as pulmonary embolism, cardiomyopathy, and left bundle branch block, and so result in false positives, according to the task force writing group. 

The expert consensus document dips into a controversial area by setting levels of cTn for MI associated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). 

"This is one of the most controversial areas in the definition of myocardial infarction," Anthony DeMaria, MD, from the University of California in San Diego and editor-in-chief of the Journal of the American College of Cardiology, told MedPage Today. 

"There are a large number of people undergoing PCI in the setting of an acute MI. It's almost impossible to know whether a subsequent increase in troponin was part and parcel of the acute MI or related to the procedure itself," DeMaria said. 

The consensus document, titled "Third Universal Definition of Myocardial Infarction," set the cTn levels for MI associated with PCI as elevation of troponin greater than 5 times the 99th percentile upper reference limit (URL) in patients with normal baseline levels or a rise in troponin values greater than 20% if the baseline values are elevated and are stable or falling. 

"Some people speculate that troponin may be too sensitive in this situation and what is needed is evidence that an elevation of some degree of troponin following a procedure actually results in some alteration of the natural history of the patient," DeMaria said. "In other words, the definition of acute MI after a procedure really is of significance if it increases the risk of subsequent events such as death." 

In CABG, the task force set the troponin values as greater than 10 x 99th percentile URL during the first 48 hours when baseline values are normal. 

DeMaria said there are several ongoing studies examining the correlation of elevated cTn with subsequent events. As this is the third definition of MI since 2000, there most likely will be more refinements as new data emerge, he said. 

The document is being copublished online in several journals including the Journal of the American College of Cardiology, Circulation, the European Heart Journal, and Global Heart. 

The task force was in touch with the FDA during the development of this new definition, which means it could be used as the basis for clinical trial protocols designed according to FDA regulations. 

"A universal definition for MI is of great benefit for clinical studies, since it will allow a standardized approach for interpretation and comparison across different trials," the task force writing group explained.When different definitions have been used in trials, it hampers "comparison and generalization between these trials," they said.

Also of significance in this document is the inclusion of imaging as a means to identify or confirm an MI. The document spells out the strengths of echocardiography, nuclear imaging, MRI, and CT in the setting of acute MI. 

"Imaging is playing an increasingly important role," DeMaria said. "In the absence of focal symptoms or with an inconclusive ECG, it's important to recognize the concomitant potential of ancillary measures, primarily imaging, to help with the diagnosis of a myocardial infarction." 

5. CDC No Longer Recommends Oral Cephalosporins for Gonorrhea 

Laurie Barclay, MD. Medscape Medical News. August 10, 2012 — The US Centers for Disease Control and Prevention (CDC) no longer recommends oral cephalosporin treatment for gonococcal infections, according to their updated guidelines, reported in the August 10 issue of the Morbidity and Mortality Weekly Report. The new recommendations update the CDC's 2010 Sexually Transmitted Diseases Treatment Guidelines. 

"Infection with [Neisseria] gonorrhoeae is a major cause of pelvic inflammatory disease, ectopic pregnancy, and infertility, and can facilitate HIV transmission," write Carlos del Rio, MD, from the Rollins School of Public Health at Emory University in Atlanta, Georgia, and colleagues. "In the United States, gonorrhea is the second most commonly reported notifiable infection, with more than 300,000 cases reported during 2011. Gonorrhea treatment has been complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials used for treatment." 

Urethral isolates of N gonorrhoeae collected in the United States during 2006 through 2011 have shown declining susceptibility to cefixime, according to an analysis of data from the CDC's Gonococcal Isolate Surveillance Project. 

Therefore, updated CDC recommendations for treatment of gonorrhea now include the following:

·         For uncomplicated gonorrhoea of the urogenital tract, rectum, or pharynx, the most reliably effective therapy is a combination regimen of 250 mg intramuscular ceftriaxone and either an oral single dose of azithromycin 1 g or a 7-day course of oral doxycycline 100 mg twice daily.
·         For first-line therapy of gonococcal infections, the CDC no longer recommends cefixime at any dose.
·         Patients given cefixime as an alternative agent should be reevaluated in 1 week for a test of cure at the infection site.
·         Patients with treatment failure, defined as persistent infection after treatment with the recommended combination therapy regimen, should undergo culture of appropriate specimens and antimicrobial susceptibility testing of N gonorrhoeae isolates using disk diffusion, Etest, or agar dilution. The laboratory should keep the isolate in case further testing is needed.
·         Within 24 hours of diagnosis, the treating clinician should report cases of treatment failure to the CDC and should obtain treatment advice from an infectious disease specialist, an STD/HIV Prevention Training Center, or the CDC.
·         Patients with treatment failure should undergo a test of cure 1 week after retreatment.
·         Patients who have urogenital or rectal gonorrhea but who have severe cephalosporin allergy should receive azithromycin 2 g in a single oral dose plus test of cure in 1 week.
·         If ceftriaxone is not available, an alternative regimen for uncomplicated gonorrhoea is a single oral dose of 400 mg cefixime plus a single oral dose of azithromycin 1 g or doxycycline 100 mg orally twice daily for 7 days, plus test of cure in 1 week.
·         Whenever possible, clinicians treating patients with gonorrhea should promptly culture and treat their patient's sex partners from the preceding 60 days. Heterosexual partners who cannot be promptly evaluated and treated may receive expedited partner therapy with oral cefixime 400 mg and azithromycin 1 g delivered to the partner by the patient, a disease investigation specialist, or via a collaborating pharmacy. 

"Treatment of patients with gonorrhea with the most effective therapy will limit the transmission of gonorrhea, prevent complications, and likely will slow emergence of resistance," the report authors conclude. "However, resistance to cephalosporins, including ceftriaxone, is expected to emerge. Reinvestment in gonorrhea prevention and control is warranted [and new] treatment options for gonorrhea are urgently needed." 

The authors have disclosed no relevant financial relationships. 

Morb Motal Wkly Rep. 2012;61:590-594. Full-text (free):  

6. ACEP Clinical Policy: Critical Issues in the Initial Evaluation and Management of Patients Presenting to the ED in Early Pregnancy 

Hahn SA, et al. Ann Emerg Med 2012;60:381-390.e28 


This clinical policy from the American College of Emergency Physicians is the revision of the 2003 Clinical Policy: Critical Issues in the Initial Evaluation and Management of Patients Presenting to the Emergency Department in Early Pregnancy.1 A writing subcommittee reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions: (1) Should the emergency physician obtain a pelvic ultrasound in a clinically stable pregnant patient who presents to the emergency department (ED) with abdominal pain and/or vaginal bleeding and a beta human chorionic gonadotropin (β-hCG) level below a discriminatory threshold? (2) In patients who have an indeterminate transvaginal ultrasound, what is the diagnostic utility of β-hCG for predicting possible ectopic pregnancy? (3) In patients receiving methotrexate for confirmed or suspected ectopic pregnancy, what are the implications for ED management? Evidence was graded and recommendations were developed based on the strength of the available data in the medical literature.

A literature search was also performed for a critical question from the 2003 clinical policy.1 Is the administration of anti-D immunoglobulin indicated among Rh-negative women during the first trimester of pregnancy with threatened abortion, complete abortion, ectopic pregnancy, or minor abdominal trauma? Because no new, high-quality articles were found, the management recommendations from the previous policy are discussed in the introduction. 


Emergency physicians frequently evaluate and manage patients with abdominal pain and/or vaginal bleeding in the first trimester of pregnancy (also referred to here as “early pregnancy”). Their primary concern in this group of patients is to identify ectopic pregnancy. The prevalence of ectopic pregnancy in symptomatic emergency department (ED) patients is as high as 13% in some series, which is much higher than the prevalence in the general population.2, 3 With wide availability of bedside ultrasound in academic EDs and increasing access in community settings, more providers are now routinely using ultrasound in their evaluation of these patients.4 

The term bedside ultrasound is used here to refer to pelvic ultrasounds that are performed in the ED by the emergency clinician, rather than in the radiology department. With the term pelvic ultrasound, the use of a transvaginal approach is implied unless transabdominal images have identified an intrauterine pregnancy. According to the 2006 ACEP policy statement Emergency Ultrasound Imaging Criteria Compendium, the primary indication for bedside ultrasound of the pelvis is to evaluate for the presence of intrauterine pregnancy, minimizing the likelihood of an ectopic pregnancy when modifying factors such as infertility treatment (putting patients at risk of heterotopic pregnancy) are not present.5 A bedside ultrasonographer may or may not visualize the adnexa. A recent meta-analysis found that bedside ultrasound performed by emergency physicians can be used as a screening tool for ectopic pregnancy.6 Pooled analysis included 10 studies and a total of 2,052 patients with 152 ectopic pregnancies; of those with ectopic pregnancy, 99.3% (95% confidence interval [CI] 96.6% to 100%) had no intrauterine pregnancy identified on bedside ultrasound.6 A comprehensive ultrasound, in contrast, is usually performed in a radiology department and is expected to include views of the uterus, adnexa, and cul-de-sac. Studies using either or both categories of ultrasound were reviewed and this distinction was highlighted in the text and Evidentiary Table. This policy is not intended to review the evidence supporting the use of bedside ultrasound by emergency physicians. 

Ultrasound has facilitated the evaluation of complications of early pregnancy; however, diagnostic algorithms still vary considerably among providers and institutions. Algorithms guiding the evaluation of abdominal pain or vaginal bleeding in early pregnancy generally incorporate the results of quantitative serum β-hCG measurements and pelvic ultrasonography. Many algorithms apply the principle of the discriminatory threshold, historically defined as the level at which the sensitivity of ultrasound was thought to approach 100% for the detection of intrauterine pregnancy; the presumptive diagnosis of ectopic pregnancy is made if an intrauterine pregnancy is not visualized when the β-hCG is above a defined cutoff. This threshold depends on what ultrasound criteria are used to define an intrauterine pregnancy and is institution, operator, and patient dependent, but is commonly reported as ranging from 1,000 to 2,000 mIU/mL for radiologist-performed transvaginal sonography.7, 8 Although the traditionally defined discriminatory threshold is widely used, its applicability to ED practice is not as well established, and the concept itself has recently been called into question.9, 10 For these reasons, this policy refers to the general concept of a discriminatory threshold, where appropriate, but the discussion is not limited to any specific β-hCG cutoff. 

The first critical question deals with the diagnostic and management variability that occurs when the clinician obtains a β-hCG result, and it is below a commonly defined discriminatory threshold. Some clinicians may not perform an ultrasound in these patients based on the incorrect assumption that an ectopic pregnancy is unlikely because the β-hCG level is low. In some settings, the emergency physician may be unable to obtain a comprehensive ultrasound in the radiology department for the same reason. However, it is well documented that ectopic pregnancies can present at almost any β-hCG level, high or low.7 Some clinicians may defer an ultrasound when the β-hCG level is below the discriminatory threshold because they think that the risk of rupture is low. However, rupture has been documented at very low β-hCG levels.7, 11 Other clinicians may defer imaging in these cases because they believe that the diagnostic utility of pelvic ultrasound is low when the β-hCG level is below the discriminatory threshold or assume that there is little harm in delaying the diagnostic ultrasound.
The emergency physician is faced with another diagnostic and management question when an ultrasound is indeterminate, also called “nondiagnostic” or a “pregnancy of unknown location.” The second critical question examines this subgroup of patients with indeterminate ultrasounds and addresses whether the initial β-hCG level can help risk-stratify these patients.

The third critical question explores the implications of methotrexate therapy for emergency medicine practice. Administration of methotrexate is an accepted and widely used alternative to laparoscopic surgery for the management of known or suspected ectopic pregnancy.12, 13, 14 Methotrexate therapy is a complex intervention, and complications of therapy are frequently evaluated in the ED… 

7. Images in Clinical Medicine 

Coronary Arteritis 

Bilateral Anterior Shoulder Dislocation 

28-year-old woman with RUQ pain

Woman With Painful Purpura

Male With Abdominal Pain

Man With Sudden Onset of Bilateral Flank Pain

Tattoo Ink–Related Nontuberculous Mycobacterial Infection

Associated editorial from the FDA:  

8.  2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With USA/Non-STEMI (Updating the 2007 Guideline and Replacing the 2011 Focused Update): A Report of the ACC Foundation/AHA Task Force on Practice Guidelines 

Keeping pace with the stream of new data and evolving evidence on which guideline recommendations are based is an ongoing challenge to timely development of clinical practice guidelines. In an effort to respond promptly to new evidence, the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) Task Force on Practice Guidelines (Task Force) has created a “focused update” process to revise the existing guideline recommendations that are affected by the evolving data or opinion. New evidence is reviewed in an ongoing fashion to more efficiently respond to important science and treatment trends that could have a major impact on patient outcomes and quality of care. Evidence is reviewed at least twice a year, and updates are initiated on an as-needed basis and completed as quickly as possible while maintaining the rigorous methodology that the ACCF and AHA have developed during their partnership of more than 20 years.  

These focused updates are prompted following a thorough review of late-breaking clinical trials presented at national and international meetings in addition to other new published data deemed to have an impact on patient care (Section 1.1, Methodology and Evidence Review). Through a broad-based vetting process, the studies included are identified as being important to the relevant patient population. The focused update is not intended to be based on a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that may affect changes to current recommendations… 

9. Predicting early death in patients with traumatic bleeding: development and validation of prognostic model 

Perel P, et al. BMJ 2012;345:e5166 

Objective To develop and validate a prognostic model for early death in patients with traumatic bleeding. 

Design Multivariable logistic regression of a large international cohort of trauma patients. 

Setting 274 hospitals in 40 high, medium, and low income countries 

Participants Prognostic model development: 20 127 trauma patients with, or at risk of, significant bleeding, within 8 hours of injury in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial. External validation: 14 220 selected trauma patients from the Trauma Audit and Research Network (TARN), which included mainly patients from the UK. 

Outcomes In-hospital death within 4 weeks of injury. 

Results 3076 (15%) patients died in the CRASH-2 trial and 1765 (12%) in the TARN dataset. Glasgow coma score, age, and systolic blood pressure were the strongest predictors of mortality. Other predictors included in the final model were geographical region (low, middle, or high income country), heart rate, time since injury, and type of injury. Discrimination and calibration were satisfactory, with C statistics above 0.80 in both CRASH-2 and TARN. A simple chart was constructed to readily provide the probability of death at the point of care, and a web based calculator is available for a more detailed risk assessment ( 

Conclusions This prognostic model can be used to obtain valid predictions of mortality in patients with traumatic bleeding, assisting in triage and potentially shortening the time to diagnostic and lifesaving procedures (such as imaging, surgery, and tranexamic acid). Age is an important prognostic factor, and this is of particular relevance in high income countries with an aging trauma population. 

10. Head Injury: Comparing CT Head Rules 

A. Prediction Value of the Canadian CT Head Rule and the New Orleans Criteria for Positive Head CT Scan and Acute Neurosurgical Procedures in Minor Head Trauma: A Multicenter External Validation Study 

Bouida W, et al. Ann Emerg Med. 2012; in press 

Study objective: The New Orleans Criteria and the Canadian CT Head Rule have been developed to decrease the number of normal computed tomography (CT) results in mild head injury. We compare the performance of both decision rules for indentifying patients with intracranial traumatic lesions and those who require an urgent neurosurgical intervention after mild head injury. 

Methods: This was an observational cohort study performed between 2008 and 2011 on patients with mild head injury who were aged 10 years or older. We collected prospectively clinical head CT scan findings and outcome. Primary outcome was need for neurosurgical intervention, defined as either death or craniotomy, or the need of intubation within 15 days of the traumatic event. Secondary outcome was the presence of traumatic lesions on head CT scan. New Orleans Criteria and Canadian CT Head Rule decision rules were compared by using sensitivity specifications and positive and negative predictive value. 

Results: We enrolled 1,582 patients. Neurosurgical intervention was performed in 34 patients (2.1%) and positive CT findings were demonstrated in 218 patients (13.8%). Sensitivity and specificity for need for neurosurgical intervention were 100% (95% confidence interval [CI] 90% to 100%) and 60% (95% CI 44% to 76%) for the Canadian CT Head Rule and 82% (95% CI 69% to 95%) and 26% (95% CI 24% to 28%) for the New Orleans Criteria. Negative predictive values for the abovementioned clinical decision rules were 100% and 99% and positive values were 5% and 2%, respectively, for the Canadian CT Head Rule and New Orleans Criteria. Sensitivity and specificity for clinical significant head CT findings were 95% (95% CI 92% to 98%) and 65% (95% CI 62% to 68%) for the Canadian CT Head Rule and 86% (95% CI 81% to 91%) and 28% (95% CI 26% to 30%) for the New Orleans Criteria. A similar trend of results was found in the subgroup of patients with a Glasgow Coma Scale score of 15. 

Conclusion: For patients with mild head injury, the Canadian CT Head Rule had higher sensitivity than the New Orleans Criteria, with higher negative predictive value. The question of whether the use of the Canadian CT Head Rule would have a greater influence on head CT scan reduction requires confirmation in real clinical practice.
B. Head CT Use in the ED for Mild TBI: Integrating Evidence Into Practice for the Resident Physician

Morton MJ, et al. Ann Emerg Med. 2012;60;361-367. 


There is a large gap between the recommendations of high-quality evidence-based guidelines and use of this evidence in routine patient care. The 2001 Institute of Medicine report titled Crossing the Quality Chasm reported that clinicians' adherence to well-established evidence is “highly uneven.”1 Multiple barriers to acceptance and implementation of evidence exist, including lack of awareness or familiarity, variable agreement, questioning of self-efficacy and outcome, and inertia.2 Given that emergency departments (EDs) manage millions of patients each year, improving evidence uptake and reducing variability in resource use will potentially yield significant benefits in terms of efficacy of care and cost-effectiveness. One example in which there is a potential gap in uptake of evidence in emergency medicine is use of head computed tomography (CT) scans in patients with mild traumatic (TBI) brain injury. 

Use of emergency neuroimaging for mild traumatic brain injury has increased dramatically during the past 15 years. According to the Centers for Disease Control and Prevention, patients with mild traumatic brain injury are defined as “those in which the injury to the brain itself is diagnosed as mild at the time the person is initially evaluated. Most…recover fully from a mild traumatic brain injury, but occasionally serious long-term consequences may occur.”3 According to recent estimates, 1.7 million patients present to US EDs annually for traumatic brain injuries3; the majority of these patients receive diagnoses of mild traumatic brain injury, most of whom are evaluated with a head CT scan despite a low incidence of clinically significant findings on head CT (5% to 9% in recent large cohorts).4, 5, 6 However, even patients initially receiving a diagnosis of mild traumatic brain injury may experience subsequent clinical deterioration to other categories of brain injury, which increases the complexity of decisionmaking with regard to this patient population.7, 8 Approximately 125,000 patients annually experience long-term consequences of traumatic brain injury,9 and the costs of mild traumatic brain injury alone are estimated at $17 billion per year.10 

According to the American College of Radiology, diagnostic imaging is the fastest-growing medical expenditure in the United States, with an annual growth rate of 9%.11 Between 1995 and 2004, the number of CT scans and magnetic resonance imaging studies ordered in US EDs almost quadrupled.12 One single-center study reported a 51% increase in the number of head CT scans ordered in an adult ED between 2000 and 2005.13 Overuse of CT scans in EDs not only increases health care costs to patients and the overall cost of US health care but also exposes patients to high doses of ionizing radiation. The high prevalence of presentations for mild traumatic brain injury to EDs, as well as the potential public health implications of unnecessary CT imaging, necessitates increased resident education about clinical decisionmaking for mild TBI… 

The remainder of the article (full-text free):  

C. Does This Patient With Minor Head Trauma Need Neuroimaging? 

Cooper DD, et al. Ann Emerg Med. 2012;60:368-369. 

11. SHOCK II: Intraaortic Balloon Pump Use for Cardiogenic Shock Questioned

By Peggy Peck, Editor-in-Chief, MedPage Today, August 27, 2012 

When myocardial infarction (MI) is complicated by cardiogenic shock, use of intraaortic balloon counterpulsation (IABP) did not reduce mortality among patients scheduled for revascularization--a finding that calls into question current guidelines for treating cardiogenic shock in this population.  

At 30 days, only 60% of the patients treated with IABP were still alive, a mortality that was no different from the rate in the control group (39.7% versus 41.3% relative risk 0.96, 95% CI 0.79-1.17, P=0.69), according to findings from the IABP-SHOCK II trial reported online by the New England Journal of Medicine. 

The findings were simultaneously reported as a Hot Line presentation at the European Society of Cardiology meeting in Munich. 

Holger Thiele, MD, from University of Leipzig-Heart Center, Leipzig, Germany, and colleagues recruited 600 patients for a randomized, prospective, open-label, multicenter trial and assigned 300 to IABP. 

While there was no mortality benefit for IABP, there also was no apparent harm:
·         Rates of major bleeding: 3.3% versus 4.4% in controls (P=0.53)
·         Rates of sepsis: 15.7% versus 20.5% (P=0.15)
·         Rates of stroke: 0.7% versus 1.7% (P=0.28)
·         Rates of peripheral ischemic complications: 4.3% versus 3.4% (P=0.53) 

Current American College of Cardiology/American Heart Association guidelines for treatment of STEMI support use of IABP in this population, but that recommendation comes from a trial "that did not address this question, it really looked at the question of revascularization of these patients," said Mariell Jessup, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia. 

The earlier trial, called SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock), "was really about bypass surgery in these patients," she said.

Jessup, who is president-elect of the American Heart Association, told MedPage Today, that the results of the IABP-SHOCK II trial "may very well be the most important finding to be reported at this meeting." She said the current Class I recommendation is for use of IABP when the patient is not stable. "It is possible that this [IABP-SHOCK II] could completely change this guideline." 

Jessup noted that use of IABP has become the norm for treating these patients and she suggested that physicians will find it hard to resist using IABP because "it is hard for physicians to not do something for these patients." 

Christopher O'Connor, MD, and Joseph Rogers, MD, echoed Jessup's view in an NEJM editorial. They are from Duke University in Durham, N.C. 

Under the title, "Evidence for Overturning the Guidelines in Cardiogenic Shock" O'Connor and Rogers wrote that data from IABP-SHOCK II, and a number of recent meta-analyses, "do not support the routine use of IABP in patients with acute myocardial infarction complicated by cardiogenic shock, and the level I guideline recommendation is now strongly challenged. Members of guideline committees and clinicians should take note of another example of a recommendation that is based on insufficient data." 

Patients in the IAPB-SHOCK trial were recruited from June 16, 2009 through March 3, 2012 at 37 centers in Germany. Thirty of the 299 patients assigned to the control group did eventually undergo IABP, usually within 24 hours of randomization, and 26 of those patients were classified as protocol violations. Likewise, 13 patients assigned to IABP did not undergo the treatment, with death being the most common reason.

The authors noted a number of limitations, starting with lack of blinding, and the failure to obtain "hemodynamic measurements or assess laboratory inflammatory markers other than blood pressure, heart rate, and C-reactive protein levels." 

Also, the mortality rate in both arms was lower than anticipated -- 40% versus a range of 42% to 48% in other studies -- suggesting that most patients in this study had mild or moderate cardiogenic shock, which could limit the generalizability of these results, they cautioned. 

"Finally, we do not yet have any information about longer-term outcomes. Since a balloon intraaortic counterpulsation was used for a median of only 3 days, it seems unlikely that any beneficial effect will become evident later than 30 days," they wrote.

Thiele H, et al. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock

N Engl J Med 2012; published online Aug 27, 2012  Abstract:  

12. External Validation of the Vancouver Chest Pain Rule 

Sensitivity was high, but the rule missed 1.4 percent of patients with acute coronary syndrome events at 30 days. 

To study the validity of the Vancouver Chest Pain Rule, researchers prospectively evaluated its performance in a convenience sample of 593 consecutive patients aged 25 and older who presented with acute chest pain to an emergency department in Iran in 2009. The primary outcome was development of acute coronary syndrome (ACS; diagnosed according to predefined criteria) within 30 days of presentation. 

The rule categorizes patients younger than 40 as low risk for ACS if they have normal initial electrocardiogram (ECG) and no history of ischemic chest pain. Patients aged 40 and older are categorized as low risk if they have normal initial ECG, no history of ischemic chest pain, chest pain that does not radiate or increase with deep breath or palpation, and either initial CK-MB below 3.0 µg/mL or CK-MB 3.0 µg/mL along with no ECG change or CK-MB or troponin rise within 2 hours of presentation (see figure). 

Use of the rule would have categorized 49.2% of study patients as low risk and eligible for discharge. Four of those patients (1.4%) developed ACS within 30 days; none of them died. The rule had a sensitivity for ACS within 30 days of 95.1%, a specificity of 56.3%, and negative and positive predictive values of 98.6% and 25.9%, respectively. Two of the four patients missed by the rule would have been identified by adding troponin-T measurement to the algorithm. 

Comment: In determining which low-risk chest pain patients are safe to discharge from the ED, the Vancouver Chest Pain rule isn't perfect, but it comes pretty close. This external validation study shows that the rule remains highly sensitive when applied outside the institution where it was developed. Although the rule doesn't integrate troponin measurement, this additional information may improve its performance. 

— Diane M. Birnbaumer, MD, FACEP. Published in Journal Watch Emergency Medicine August 24, 2012. Citation: Jalili M et al. Validation of the Vancouver Chest Pain Rule: A prospective cohort study. Acad Emerg Med 2012 Jul; 19:837. Abstract: 

The Vancouver Chest Pain Rule:  

13. Diagnosis and Management of Hereditary Angioedema: An Emergency Medicine Perspective 

Moellman JJ, et al. J Emerg Med. 2012;43:391-400. 

Background: Hereditary angioedema (HAE) is a rare and often debilitating condition associated with substantial morbidity and mortality in the absence of appropriate intervention. An underlying deficiency in functional C1-inhibitor (C1-INH) protein induces a vulnerability to unchecked activation of the complement, contact, and coagulation/fibrinolytic systems. The clinical consequence is a pattern of recurring attacks of non-pitting, non-pruritic edema, the urgency of which varies by the affected site. Laryngeal edema can escalate rapidly to asphyxiation, and severe cases of abdominal swelling can lead to hypovolemic shock.

Objectives: This report reviews the emergency diagnosis and treatment of hereditary angioedema and the impact of recently introduced treatments on treatment in the United States. 

Discussion: Until recently, emergency physicians in the United States were hindered by the lack of rapidly effective treatment options for HAE attacks. In this article, general clinical and laboratory diagnostic procedures are reviewed against the backdrop of two case studies: one patient presenting with a known history of HAE and one with previously undiagnosed HAE. In many countries outside the United States, plasma-derived C1-INH concentrate has for decades been the first-line treatment for acute attacks. The end of 2009 ushered in a new era in the pharmacologic management of HAE attacks in the United States with the approval of two new treatment options for acute treatment: a plasma-derived C1-INH concentrate and a kallikrein inhibitor. 

Conclusion: With access to targeted and effective treatments, emergency physicians are now better equipped for successful and rapid intervention in urgent HAE cases.

14. Some children genetically predisposed to convert codeine to dangerous levels of morphine 

Aug. 15 (HealthDay News) -- Some children may be at risk for serious adverse events, including death, after taking codeine for relief of pain following tonsillectomy and/or adenoidectomy for obstructive sleep apnea, according to a safety communication issued Aug. 15 by the U.S. Food & Drug Administration. 

The agency issued the alert after reviewing recent reports of three deaths and one case of severe respiratory depression in children 2 to 5 years of age who took the pain reliever after surgery. The children were given the pain reliever within a normal range of dosage, but each had an inherited genetic ability to convert the painkiller into life-threatening or fatal amounts of morphine. 

The FDA is currently conducting a safety review of the drug to see if other children have died or overdosed after ingesting codeine and, if so, whether or not they were taking the drug for reasons other than pain relief after surgery to treat obstructive sleep apnea. 

According to the FDA, "Health care professionals should be aware of the risks of using codeine in children, particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. If prescribing codeine-containing drugs, the lowest effective dose for the shortest period of time should be used on an as-needed basis." 

15. Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial (shows no benefit) 

Venekamp RP, et al. CMAJ 2012 Aug 7. [Epub ahead of print] 

Background: Patients with acute rhinosinusitis are frequently encountered in primary care. Although corticosteroids are being increasingly used for symptom control, evidence supporting their use is inconclusive. We conducted a randomized controlled trial to examine the effectiveness of systemic corticosteroid monotherapy for clinically diagnosed, uncomplicated acute rhinosinusitis. 

Methods: We conducted a block-randomized, double-blind, placebo-controlled clinical trial at 54 primary care practices (68 family physicians) in the Netherlands between Dec. 30, 2008, and Apr. 28, 2011. Adult patients with clinically diagnosed acute rhinosinusitis were randomly assigned to receive either prednisolone 30 mg/d or placebo for 7 days and asked to complete a symptom diary for 14 days. The primary outcome measure was the proportion of patients with resolution of facial pain or pressure on day 7.  

Results: Of the 185 patients included in the trial (93 in the treatment group, 92 in the placebo group), 2 withdrew from the study and 9 were excluded from the primary analysis because of incomplete symptom reporting. The remaining 174 patients (88 in the treatment group, 86 in the placebo group) were included in the intention-to-treat analysis. The proportions of patients with resolution of facial pain or pressure on day 7 were 62.5% (55/88) in the prednisolone group and 55.8% (48/86) in the placebo group (absolute risk difference 6.7%, 95% confidence interval –7.9% to 21.2%). The groups were similar with regard to the decrease over time in the proportion of patients with total symptoms (combined symptoms of runny nose, postnasal discharge, nasal congestion, cough and facial pain) and health-related quality of life. Adverse events were mild and did not differ significantly between the groups.  

Interpretation: Systemic corticosteroid monotherapy had no clinically relevant beneficial effects among patients with clinically diagnosed acute rhinosinusitis. 

16. ECG of the Month at Medscape 

Here’s a good collection of images with questions and interpretations 

17. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. 

Pearce MS, et al. Lancet. 2012 Aug 4;380(9840):499-505. 

BACKGROUND: Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. 

METHODS: In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. 

FINDINGS: During follow-up, 74 of 178,604 patients were diagnosed with leukaemia and 135 of 176,587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p less than 0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03). 

INTERPRETATION: Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10,000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. 

FUNDING: US National Cancer Institute and UK Department of Health. 

18. Clinical Reviews 

A. A Primer on the Surgical Airway  

Rich Levitan, MD, Emergency Physicians Monthly. August 5, 2012 

B. Dopamine Versus Norepinephrine for the Treatment of Septic Shock  

Sandifer JP, et al. Ann Emerg Med 2012;60:372-373. 

Take-Home Message: Dopamine administration is associated with a higher incidence of arrhythmias and increased risk of death compared with norepinephrine in the treatment of septic shock. 

19. Hospital-Wide Solutions Needed to Reduce ED Crowding 

Troy Brown. Medscape Medical News. August 10, 2012 — Crowding in hospital emergency departments (EDs) harms patients and limits hospitals' ability to meet national safety and quality goals. Instead of focusing only on ED practices, administrators need to improve the way admitted patients are moved out of the ED and into inpatient beds, according to an article published in the August issue of Health Affairs. 

Elaine Rabin, MD, an assistant professor in the Department of Emergency Medicine at the Mount Sinai School of Medicine in New York City, and colleagues both describe the problems associated with the practice of boarding patients in the ED and offer potential solutions. 

The authors report that a national survey published in 2010 showed that in the week before the survey, 84.9% of hospitals had boarded patients. 

Dangerous for Patients, Costly for Hospitals 

Patient boarding occurs when the order to admit the patient has been written, but there is no inpatient bed available. When this happens, patients are typically kept on a stretcher or bed in the ED hall until a bed becomes available. They are then cared for by members of the ED staff, who must also care for their full load of ED patients. Patients kept as boarders have increased morbidity and mortality, longer hospital stays, inadequate pain control, and inferior care in general. 

"Holding admitted patients in crowded conditions carries well-documented risks, including prolonged illness and worse outcomes for stroke, cardiac, and intubated patients; exposure to hospital-acquired infections; and lapses in daily medications and other routine care from overtaxed emergency department staff," the authors write. 

Patient boarding costs hospitals money by decreasing the number of patients the ED can care for and lengthening the time patients must wait to get treated. Physicians also may be less inclined to send patients to EDs that are known for long wait times. "One Pennsylvania hospital estimated that boarding patients more than two hours costs the hospital more than $3 million annually when it must turn away new patients," the authors write. 

A number of factors throughout the system influence the availability of inpatient beds, note the authors. "Theoretically, backups occur at the following points in time: when hospital capacity is exceeded, and the hospital is full of patients who need inpatient care; when the hospital inefficiently manages and discharges inpatients, unnecessarily tying up inpatient beds; or when empty beds exist but are unavailable to emergency department patients — for example, when beds are reserved for other possible admissions," they write. 

Most problems result not from exceeded hospital capacity but, rather, from inefficiencies that can be fixed. For example, many hospitals offer certain services only during business hours, which can delay patient discharges. Better management of these types of services can help facilitate discharges. 

In addition, the authors explain, according to "queuing theory, boarding occurs before hospitals and units are 100 percent occupied, usually around 80–85 percent capacity. This is partly because specific bed types, such as beds for males or beds for isolation cases, fill earlier than other types." 

Solutions Exist, Are Underused 

Some of the solutions to the problem of patient boarding are actually fairly simple, the authors say. One such remedy is to move admitted patients from the ED hallway to a hallway on an inpatient unit. Patients are happier there because it is quieter, and they usually get better care because patient–nurse ratios there are lower than in the ED. In addition, the authors report that inpatient beds are often found quickly for patients boarding on inpatient units. 

Reducing the number of unused hospital beds will also help decrease the need for patient boarding. "One recent informal survey found that more than 60 percent of teaching hospitals board patients in the emergency department even when beds are empty elsewhere in the hospital," the authors write. 

Many times empty hospital beds are reserved for patients expected from other hospitals or in anticipation of possible admissions after elective procedures. Sometimes beds remain empty for geographic or staffing reasons, either to keep patients with certain conditions in close proximity to each other or to make it easier for hospital staff. 

"Surgical schedule smoothing" eliminates some of the peaks that occur as a result of many surgeons' preference for scheduling surgeries early in the week; spacing elective procedures throughout the week ensures that beds will be available. 

Current methods aimed at reducing patient boarding are a good start, but they could be strengthened, the authors note. Beginning in 2014, the Centers for Medicare and Medicaid Services will institute a pay-for-reporting program with financial incentives for reporting on hospital performance metrics including ED length-of-stay for admitted and discharged patients and boarding times. The authors suggest that the pay-for-performance program should also incur penalties for failing to reduce wait times. 

The Joint Commission has recently required hospitals to address boarding for the purposes of accreditation; these requirements could be strengthened by making them more specific in terms of percentages of patients expected to board in the ED for less than 4 hours. 

"Boarding is a systemwide problem, and successful responses require the endorsement of hospital leaders," the authors conclude. "Proven strategies to reduce boarding are grossly underused." 

Educating hospital administrators and patients may not be enough. "If continued education of hospital managers and the public does not result in change, enhanced regulation will be necessary to protect patients," the authors add. 

The authors are all members of the Emergency Department Crowding Interest Group of the Society for Academic Emergency Medicine, and the article was submitted on the group’s behalf. The authors have disclosed no relevant financial relationships. 

Health Aff. 2012;31:1757-1766. Abstract:  

20. Utilization and Yield of Chest CT Angiography Associated with Low Positive D-dimer Levels 

Huckins DS, et al. J Emerg Med. 2012;43:211-220.  

Background: It is unclear to what degree broadly applied D-dimer testing combined with a low threshold for imaging with even minimally positive results may be contributing to the utilization of chest computed tomographic angiography (CTA). 

Study Objectives: To determine what proportion of chest CTAs for suspected pulmonary embolism (PE) were performed in the setting of minimally elevated D-dimer levels, and to determine the prevalence of PE in those patients when stratified by clinical risk. 

Methods: Retrospective chart review of all patients who had chest CTA for the evaluation of suspected PE during the years 2002–2006 in a suburban community teaching hospital emergency department. 

Results: There were 1136 eligible patient visits, of which 353 (31.1%) were found to have D-dimer levels in the low positive range (0.5–0.99 μg/mL). Of these 353 patients, 9 (2.6%; 95% confidence interval [CI] 0.9–4.2%) were diagnosed with PE. There were also 109 patients (9.6%) who had normal D-dimer levels (below 0.5 μg/mL). Two of these 109 (1.8%; 95% CI 0–4.2%) were diagnosed with PE. When stratified by the Pulmonary Embolism Rule-out Criteria, 99 of 353 patients with low positive D-dimer levels (28.0%; 95% CI 23.4–32.7%), and 14 of 109 with normal D-dimer levels (12.8%; 95% CI 6.6–19.1%) were classified as low risk, none of whom had PE. 

Conclusions: Nearly one-third of all chest CTAs were done for patients with minimally elevated D-dimer levels, and another 9.6% for patients with normal D-dimer levels with very low yield. Further research to define clinical criteria identifying patients with minimal risk of PE despite low positive D-dimer levels represents an opportunity to improve both patient safety and utilization efficiency of chest CTA. 

21. Burnout and Satisfaction With Work-Life Balance Worse Among US Physicians Relative to the General US Population 

Shanafelt TD, et al. Arch Intern Med. August 20, 2012. [epub ahead of print]

Background  Despite extensive data about physician burnout, to our knowledge, no national study has evaluated rates of burnout among US physicians, explored differences by specialty, or compared physicians with US workers in other fields. 

Methods  We conducted a national study of burnout in a large sample of US physicians from all specialty disciplines using the American Medical Association Physician Masterfile and surveyed a probability-based sample of the general US population for comparison. Burnout was measured using validated instruments. Satisfaction with work-life balance was explored. 

Results  Of 27 276 physicians who received an invitation to participate, 7288 (26.7%) completed surveys. When assessed using the Maslach Burnout Inventory, 45.8% of physicians reported at least 1 symptom of burnout. Substantial differences in burnout were observed by specialty, with the highest rates among physicians at the front line of care access (family medicine, general internal medicine, and emergency medicine). Compared with a probability-based sample of 3442 working US adults, physicians were more likely to have symptoms of burnout (37.9% vs 27.8%) and to be dissatisfied with work-life balance (40.2% vs 23.2%) (P less than .001 for both). Highest level of education completed also related to burnout in a pooled multivariate analysis adjusted for age, sex, relationship status, and hours worked per week. Compared with high school graduates, individuals with an MD or DO degree were at increased risk for burnout (odds ratio [OR], 1.36; P less than .001), whereas individuals with a bachelor's degree (OR, 0.80; P = .048), master's degree (OR, 0.71; P = .01), or professional or doctoral degree other than an MD or DO degree (OR, 0.64; P = .04) were at lower risk for burnout. 

Conclusions  Burnout is more common among physicians than among other US workers. Physicians in specialties at the front line of care access seem to be at greatest risk. 

22. Beware the Nocebo Effect 

By Paul Enck and Winfried Huaser. New York Times. August 10, 2012 

EVERYONE knows that a placebo — a fake medication or sham procedure, typically used as a control in a medical trial — can nonetheless have a positive effect, relieving real symptoms like pain, bloating or a depressed mood. The placebo effect is a result of the patient’s expectation that the treatment will help.  

But expectations can also do harm. When a patient anticipates a pill’s possible side effects, he can suffer them even if the pill is fake. This “nocebo” effect has been largely overlooked by researchers, clinicians and patients. In an article recently published in the journal Deutsche Ärzteblatt International [see link to full-text below], we and our colleague Ernil Hansen reviewed 31 studies, conducted by us and other researchers, that demonstrated the nocebo effect. We urge doctors and nurses to be more mindful of its dangers, particularly when informing patients about a treatment’s potential complications.  

Consider the number of people in medical trials who, though receiving placebos, stop participating because of side effects. We found that 11 percent of people in fibromyalgia drug trials who were taking fake medication dropped out of the studies because of side effects like dizziness or nausea. Other researchers reported that the discontinuation rates because of side effects in placebo groups in migraine or tension drug trials were as much as 5 percent. Discontinuation rates in trials for statins ranged from 4 percent to 26 percent.  

In a curious study, a team of Italian gastroenterologists asked people with and without diagnosed lactose intolerance to take lactose for an experiment on its effects on bowel symptoms. But in reality the participants received glucose, which does not harm the gut. Nonetheless, 44 percent of people with known lactose intolerance and 26 percent of those without lactose intolerance complained of gastrointestinal symptoms.  

In one remarkable case, a participant in an antidepressant drug trial was given placebo tablets — and then swallowed 26 of them in a suicide attempt. Even though the tablets were harmless, the participant’s blood pressure dropped perilously low.  

The nocebo effect can be observed even when people take real, non-placebo drugs. When medical professionals inform patients of possible side effects, the risk of experiencing those side effects can increase. In one trial, the drug finasteride was administered to men to relieve symptoms of prostate enlargement. Half of the patients were told that the drug could cause erectile dysfunction, while the other half were not informed of this possible side effect. In the informed group, 44 percent of the participants reported that they experienced erectile dysfunction; in the uninformed group, that figure was only 15 percent.  

In a similar experiment, a group of German psychologists took patients with chronic lower back pain and divided them into two groups for a leg flexion test. One group was told that the test could lead to a slight increase in pain, while the other group was told that the test had no effect on pain level. The first group reported stronger pain and performed fewer leg flexions than the second group did.  

A doctor’s choice of words matters. A team of American anesthesiologists studied women about to give birth who were given an injection of local anesthetic before being administered an epidural. For some women, the injection was prefaced by the statement, “We are going to give you a local anesthetic that will numb the area so that you will be comfortable during the procedure.” For others, the statement was, “You are going to feel a big bee sting; this is the worst part of the procedure.” The perceived pain was significantly greater after the latter statement, which emphasized the downside of the injection.  

The nocebo effect presents doctors and nurses with an ethical dilemma: on one hand, they are required to tell patients about the potential complications of a treatment; on the other hand, they want to minimize the likelihood of side effects. But if merely telling patients about side effects increases their likelihood, what is to be done?  

Better communication is the answer. When talking with patients, doctors and nurses often say things with unintended negative suggestions, like “it’s just going to bleed a bit” or “you must avoid lifting heavy objects — you don’t want to end up paralyzed.” We recommend more extensive training in communication for doctors and nurses, to help them use the power of their words appropriately. As the great cardiologist Bernard Lown once said, “Words are the most powerful tool a doctor possesses, but words, like a two-edged sword, can maim as well as heal.”  

Paul Enck is a professor of psychology at the University of Tübingen. Winfried Häuser is an associate professor of psychosomatic medicine at the University of Munich. 

Häuser W, Hansen E, Enck P. Nocebo phenomena in medicine: their relevance in everyday clinical practice. Dtsch Arztebl Int. 2012 Jun;109(26):459-65. Full-text (free):  

23. Just FYI 

A. The Beginning of the End of AIDS? 

Havlir D, et al. N Engl J Med 2012; 367:685-687  

We are at a moment of extraordinary optimism in the response to the human immunodeficiency virus (HIV). A series of scientific breakthroughs, including several trials showing the partial efficacy of oral and topical chemoprophylaxis1,2 and the first evidence of efficacy for an HIV vaccine candidate,3 have the potential to markedly expand the available preventive tools. There is evidence of the first cure of an HIV-infected person. And most important, the finding that early initiation of antiretroviral therapy can both improve individual patient outcomes and reduce the risk of HIV transmission to sexual partners by 96%4 has led many to assert what had so long seemed impossible: that control of the HIV pandemic may be achievable… 

The remainder of the essay (full-text free):  

B. Bariatric Surgery Reduces Incident Type 2 Diabetes among Obese Patients 

In this report from the Swedish Obese Subjects study, the rate of incident type 2 diabetes in usual-care and bariatric-surgery groups was 28.4 and 6.8 cases per 1000 person-years, respectively. These findings suggest that surgery is much more efficient than usual care. 

C. Trial Will Test Methotrexate for MI, Stroke Prevention 

By John Gever, Senior Editor, MedPage Today. Published: August 23, 2012 

The possibility that the immunosuppressant drug methotrexate can prevent major cardiovascular events will be tested in a 7,000-patient randomized trial funded by the federal government.

Called the Cardiovascular Inflammation Reduction Trial (CIRT), the 4-year secondary prevention study is sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and will be led by Paul Ridker, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston, as principal investigator. 

D. West Nile Virus 

Information for Patients 

Goodman DM, et al. JAMA. Published online August 24, 2012. 

Physician Update from CDC 

E. Detecting Obstructive Coronary Disease With CT Angiography and Noninvasive Fractional Flow Reserve  

Patel MR, et al. JAMA. Published online August 26, 2012. 

Physicians commonly encounter patients reporting chest discomfort. In these cases, the physician needs to determine whether the patient has obstructive coronary artery disease (CAD), and if so, whether the patient is at increased risk of future cardiovascular events. The ultimate goal of this evaluation is to direct optimal medical therapy and potentially lead to ischemia-driven coronary revascularization. The fractional flow reserve (FFR) performed during invasive coronary angiography has been shown to provide lesion-specific data on ischemia, which, when used to direct revascularization, leads to improved clinical outcomes.1 - 2 Fractional flow reserve is the ratio of the mean coronary artery pressure distal to an obstructive coronary lesion relative to the mean aortic pressure during maximal coronary blood flow and represents a physiologic measure of coronary stenosis.

Current guidelines recommend that this evaluation should be differential based on patient pretest risk assessment. Low-risk patients should receive only expectant management, intermediate-risk patients should be referred for noninvasive testing, and high-risk patients should undergo invasive cardiac catheterization.3 To date, noninvasive tests have performed this evaluation by taking either an anatomic approach such as computed tomographic (CT) angiography to identify obstructive CAD or a functional approach to determine ischemia by perfusion or wall motion function via a variety of stress and imaging modes. Therefore, technologies that provide both a highly sensitive anatomic evaluation for obstructive disease and a highly specific physiologic evaluation for ischemia represent the “holy grail” for noninvasive imaging for CAD. 

It is with this background that Min et al4 report the findings of the DeFACTO study in this issue of JAMA evaluating CT angiography with a novel noninvasive FFR computed from CT (FFRCT) compared with the reference standard of invasive FFR determined by conventional coronary angiography… 

The remainder of the editorial (full-text currently free):  

Cf also Diagnostic Accuracy of Fractional Flow Reserve from Anatomic CTA for CAD 

Min JK, et al. JAMA Published online August 26, 2012