Saturday, June 22, 2013

Lit Bits: June 22, 2013

From the recent medical literature...

1. One in 604 flights have medical emergencies 

Of the 7,198,118 flights between January 2008 and October 2010, 11,920 had in-flight medical emergencies, or 1 in every 604 flights, according to a study published in the New England Journal of Medicine. A health care provider was available to help in 75% of cases. Researchers said that the most common causes of in-flight emergencies were syncope, respiratory symptoms and gastrointestinal problems. 

Peterson DC, et al. Outcomes of Medical Emergencies on Commercial Airline Flights. N Engl J Med 2013; 368:2075-2083.  

Background: Worldwide, 2.75 billion passengers fly on commercial airlines annually. When in-flight medical emergencies occur, access to care is limited. We describe in-flight medical emergencies and the outcomes of these events. 

Methods: We reviewed records of in-flight medical emergency calls from five domestic and international airlines to a physician-directed medical communications center from January 1, 2008, through October 31, 2010. We characterized the most common medical problems and the type of on-board assistance rendered. We determined the incidence of and factors associated with unscheduled aircraft diversion, transport to a hospital, and hospital admission, and we determined the incidence of death. 

Results: There were 11,920 in-flight medical emergencies resulting in calls to the center (1 medical emergency per 604 flights). The most common problems were syncope or presyncope (37.4% of cases), respiratory symptoms (12.1%), and nausea or vomiting (9.5%). Physician passengers provided medical assistance in 48.1% of in-flight medical emergencies, and aircraft diversion occurred in 7.3%. Of 10,914 patients for whom postflight follow-up data were available, 25.8% were transported to a hospital by emergency-medical-service personnel, 8.6% were admitted, and 0.3% died. The most common triggers for admission were possible stroke (odds ratio, 3.36; 95% confidence interval [CI], 1.88 to 6.03), respiratory symptoms (odds ratio, 2.13; 95% CI, 1.48 to 3.06), and cardiac symptoms (odds ratio, 1.95; 95% CI, 1.37 to 2.77). 

Conclusions: Most in-flight medical emergencies were related to syncope, respiratory symptoms, or gastrointestinal symptoms, and a physician was frequently the responding medical volunteer. Few in-flight medical emergencies resulted in diversion of aircraft or death; one fourth of passengers who had an in-flight medical emergency underwent additional evaluation in a hospital. (Funded by the National Institutes of Health.) 

See associated animated video for crisp summary (link above). 

2. Inhaled Adrenaline No Better than Inhaled Saline for Infants with Acute Bronchiolitis 

Skjerven HO, et al. N Engl J Med 2013; 368:2286-2293.  

Background: Acute bronchiolitis in infants frequently results in hospitalization, but there is no established consensus on inhalation therapy — either the type of medication or the frequency of administration — that may be of value. We aimed to assess the effectiveness of inhaled racemic adrenaline as compared with inhaled saline and the strategy for frequency of inhalation (on demand vs. fixed schedule) in infants hospitalized with acute bronchiolitis. 

Methods: In this eight-center, randomized, double-blind trial with a 2-by-2 factorial design, we compared inhaled racemic adrenaline with inhaled saline and on-demand inhalation with fixed-schedule inhalation (up to every 2 hours) in infants (younger than 12 months of age) with moderate-to-severe acute bronchiolitis. An overall clinical score of 4 or higher (on a scale of 0 to 10, with higher scores indicating more severe illness) was required for study inclusion. Any use of oxygen therapy, nasogastric-tube feeding, or ventilatory support was recorded. The primary outcome was the length of the hospital stay, with analyses conducted according to the intention-to-treat principle. 

Results: The mean age of the 404 infants included in the study was 4.2 months, and 59.4% were boys. Length of stay, use of oxygen supplementation, nasogastric-tube feeding, ventilatory support, and relative improvement in the clinical score from baseline (preinhalation) were similar in the infants treated with inhaled racemic adrenaline and those treated with inhaled saline (P above 0.1 for all comparisons). On-demand inhalation, as compared with fixed-schedule inhalation, was associated with a significantly shorter estimated mean length of stay — 47.6 hours (95% confidence interval [CI], 30.6 to 64.6) versus 61.3 hours (95% CI, 45.4 to 77.2; P=0.01) — as well as less use of oxygen supplementation (in 38.3% of infants vs. 48.7%, P=0.04), less use of ventilatory support (in 4.0% vs. 10.8%, P=0.01), and fewer inhalation treatments (12.0 vs. 17.0, P less than 0.001). 

Conclusions: In the treatment of acute bronchiolitis in infants, inhaled racemic adrenaline is not more effective than inhaled saline. However, the strategy of inhalation on demand appears to be superior to that of inhalation on a fixed schedule. (Funded by Medicines for Children; number, NCT00817466; EudraCT number, 2009-012667-34.) 

3. Biomarkers May Diagnose Mild Brain Injury 

By Nancy Walsh, Staff Writer, MedPage Today. June 20, 2013 

A combination of two biomarkers helped identify patients with mild traumatic brain injury (TBI), and one of the markers also could predict which patients would have abnormalities on head CT, researchers reported, opening the possibility for reducing the number of scans performed in emergency departments. 

The area under the receiver operator characteristic curve (AUC) for the markers S100B plus apolipoprotein A1 (apoA-1) in diagnosing TBI was 0.738 (95% CI 0.71-0.77), which was higher than for S100B alone (0.709, 95% CI 0.68-0.74, P=0.001) or for apoA-1 alone (0.645, 95% CI 0.61-0.68, P less than 0.0001), according to Jeffrey J. Bazarian, MD, of the University of Rochester in New York, and colleagues. In addition, the AUC for predicting abnormalities on an initial head CT scan for S100B was 0.694 (95% CI 0.62 to 0.77). With a cutoff level for S100B of 0.060 mcg/L, which represents a sensitivity level of 98%, 22.9% of CT scans would not be needed, the researchers reported online in the Journal of Neurotrauma. 

Each year, an estimated 1.7 million Americans experience a TBI and are at subsequent risk for long-term morbidities including cognitive disability and neurologic disorders. To date, diagnosis has relied on patient or witness reports and subjective symptoms, and no objective diagnostic test is available in the U.S. 

"As an emergency provider, I think we could have used a test like this a long time ago," Bazarian told MedPage Today. "Most of the time with patients who may have concussion I'm guessing. They often can't tell me if they've been knocked out because they're intoxicated, demented, or otherwise can't remember," he said. 

Serum S100B is a protein derived from astrocytes that is already used to screen patients before head CT scanning in 17 countries in Europe and Asia. "We are learning more about the importance of astrocytes, such as that they are responsible for the care and feeding of neurons," Bazarian explained. When measured within 3 hours of the head injury, S100B has been shown to be highly sensitive for CT abnormalities, but lacks in specificity because of its presence in melanocytes and adipocytes and its release after non-cranial injuries. 

ApoA-1 is the protein that carries high-density lipoprotein particles. Unlike S100B, it's not a brain protein, but is intimately involved in recovery from brain injury through its ability to help clear broken down neurons, which consist mainly of fat, he said. 

A proteomic screen of patients with mild TBI suggested that levels of S100B and ApoA-1 might help increase the accuracy of prediction, so the researchers prospectively studied 787 patients with mild TBI, comparing them with 467 controls. 

Median levels of S-100B were higher in cases than controls (0.149 mcg/L versus 0.071 mcg/L, P less than 0.0001), while mean levels of apoA-1 were lower in cases (0.834 mg/mL versus 0.950 mg/mL, P less than 0.0001). 

S100B alone correctly diagnosed mild TBI in 38.1% of cases using a cutoff of 90% for both sensitivity and specificity, while apoA-1 alone identified 30.4%. But the number correctly identified with both markers at that cutoff for sensitivity and specificity increased to 45.2%, which was a significant difference (P less than 0.0001). 

In evaluating the efficacy for predicting abnormalities on head CT, the researchers found that only S100B was predictive, and that adding apoA-1 didn't increase the AUC of S100B alone. 

A 90% sensitivity cutoff for S100B, with a threshold level of 0.097 mcg/L, could have avoided head CT in 30.5% of patients, but would have missed six cases, which included intraventricular hemorrhages, subdural hemorrhages, and edema. But with the higher cutoff of 98% sensitivity and a threshold of 0.060 mcg/L, only one case would have been missed -- a patient with a small cerebral contusion whose S100B level was 0.06 mcg/L. If the threshold were lowered further, to 0.10 mcg/L, the sensitivity for correctly predicting abnormalities on head CT would be 86% (95% CI 73-95). The choice of which cutoff to use would depend on the clinician's tolerance for uncertainty in specific circumstances, Bazarian noted. 

Cutting down on the need for CT scans for head-injured patients would be beneficial in reducing radiation exposure and also for unclogging emergency departments, Bazarian noted. "Much of the delay in emergency departments is caused by patients waiting for CT scans, and 95% of concussion patients have an absolutely normal head CT. A blood test could greatly reduce the number of patients needing the imaging test," he said. 

The researchers also found that the AUC for S100B was higher in adults than children and among whites compared with blacks (P less than 0.0001 for both). Accordingly, development of a multivariate model that includes not only marker levels but also adjusts for age and race could be useful, he noted. 

"This study is notable for several 'firsts.' It is the first large, multicentered brain marker study in North America, the first brain marker study to combine the clinical utility of two markers, the first to determine marker accuracy in ethnic and racial subgroups, and the first to employ the peripheral protein, apoA-1," Bazarian and colleagues wrote. 

If the FDA were to consider approving a biomarker test for mild TBI, they would be looking for data accumulated in North America. "This study is a first step toward trying to get approval in the U.S.," he said. 

Limitations of the study included the possibility of inter-reader variations in CT scan interpretation and demographic differences between the patient and control groups. Bazarian and one co-author have a patent pending for a method of diagnosing mild TBI. Bazarian also has consulted for Banyan Biomarkers and Roche Diagnostics. 

Bazarian J, et al. Classification accuracy of serum apoA-1 and S100B for the diagnosis of mild TBI and prediction of abnormal initial head CT scan" J Neurotrauma 2013 June 13 [Epub ahead of print] Abstract:  

4. Contrast Is Unnecessary for Most Abdominal CTs: Lit Review  

Richard Bukata, MD, Emergency Physicians Monthly, June 10, 2013 

A growing body of research flies in the face of this common radiology practice. 

The routine use of contrast (both oral and IV, and certainly rectal) is unnecessary for the majority of abdominal CT scans performed in the ED.  At least that is what the literature says over and over. 

Unfortunately, many radiologists disagree.  Is their objection based on a sound analysis of the literature?  Hardly.  In most cases it is a matter of personal preference.  They have been using contrast since their residency, or at least since CTs came on the scene, and just feel more comfortable with it. Have they made an honest effort to compare results with and without contrast ?  Probably not.  Do they care that oral contrast will add about two hours to an ED stay and, even when given, frequently doesn’t get to the cecum?  Probably not. 

But when the use of contrast is subject to the intense searchlight of scientific inquiry, the answer seems to be pretty clear.  It is the atypical patient with nontraumatic abdominal pain who needs contrast.   

Before we take on the “contrast, no contrast” arm wrestle, we need to take a major step back and ask, “Why are we doing so many abdominal CTs in the first place?” I won’t spend this column making the case for why clinical exam can make many CTs unnecessary. That could be an entire column. What I want to talk about is the use of ultrasonography as a first test to visualize the abdominal contents and then, and only then, considering CT if results are equivocal and imaging is still felt to be necessary. This would be a dramatic departure from our current testing culture, where CTs are the new CBCs (don’t call the surgeon without one!). 

Even the American College of Radiology has taken the radical position that, at least in children with suspected appendicitis, an ultrasound should be considered as an option. Why not in all ages and why not use some stronger language than “should be considered”? We’ll need to be satisfied with baby steps since it would likely be the uncommon radiologist in the U.S. who would actively promote following this advice. But here’s exactly what the ACR says. (As an aside, this is one of the ACR’s five “Choosing Wisely” recommendations.) 

Don’t do computed tomography (CT) for the evaluation of suspected appendicitis in children until after ultrasound has been considered as an option.

Although CT is accurate in the evaluation of suspected appendicitis in the pediatric population, ultrasound is nearly as good in experienced hands. Since ultrasound will reduce radiation exposure, ultrasound is the preferred initial consideration for imaging examination in children. If the results of the ultrasound exam are equivocal, it may be followed by CT. This approach is cost-effective, reduces potential radiation risks and has excellent accuracy, with reported sensitivity and specificity of 94 percent. 

Seems American radiologists don’t have nearly the experience (read: skill + confidence) of their European brethren in embracing this “ultrasound first” approach, but a two week course in Cancun would likely go a long way towards solving the problem. EPs can help them get this experience by ordering the correct test in these cases – an ultrasound and not a CT.  EPs need to stop aiding and abetting this process.  And we need to cite the support of the ACR so we don’t look like a bunch of no-nothing radicals.

But we’ll stick with the issue at hand – contrast in abdominal CTs. So, how about some papers indicating that oral contrast is a waste of time in the setting of suspected appendicitis – the most common setting in which oral contrast is used.   

Instead of tediously going through study after study on this topic, here are two analyses, one published in 2010 involving seven high-quality trials and another in 2005 involving 23 trials. And yes, if you’re wondering, the answer to this dilemma was clearly known as far back as 2005! And catch the concluding sentence in the 2005 paper: the diagnostic accuracy of CT without contrast “was at least as comparable” as with contrast in assessing appendicitis. In fact, the data shows it was a little better… 

5. Medication Side Effects 

A. Co prescription of statins and antibiotics linked to extra deaths 

Patel AM, et al. Ann Intern Med. 2013 Jun 18;158(12):869-76. 

BACKGROUND: Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4. 

OBJECTIVE: To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin. 

DESIGN: Population-based cohort study. 

SETTING: Ontario, Canada, from 2003 to 2010. 

PATIENTS: Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72 591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68 478). 

MEASUREMENTS: The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription. 

RESULTS: Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]). 

LIMITATIONS: Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive. 

CONCLUSION: In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity. 

B. FQs may raise kidney injury risk, study says 

Men who took fluoroquinolones had a twofold greater risk of developing serious kidney problems than nonusers, according to a study published online in the Canadian Medical Association Journal. The risk of kidney injury was nearly five times higher in men who simultaneously took a fluoroquinolone and an ACE inhibitor compared with those who didn't take fluoroquinolones. 

C. Statin Use Tied to Strains and Sprains

Muscle pain has been associated with statin use, but new evidence suggests a link with skeletal adverse events as well, a propensity-matched study found.  

6. The Clinical Use of Prothrombin Complex Concentrate 

Ferreira J, et al. J Emerg Med. 2013;44:1201-1210. 

Background: Prothrombin complex concentrate (PCC) is an inactivated concentrate of factors II, IX, and X, with variable amounts of factor VII. Guidelines recommend the use of PCC in the setting of life-threatening bleeds, but little is known on the most effective dosing strategies and how the presenting international normalized ratio affects response to therapy. 

Objectives; This review aims to highlight available data on monitoring techniques, address shortcomings of currently available data, the reversal of life-threatening and critical bleeds with PCC, and how this product compares to other therapeutic options used in critically ill patients. 

Discussion; PCC has been identified as a potential therapy for critically bleeding patients, but patient-specific factors, product availability, and current data should weigh the decision to use it. Most data exist regarding patients experiencing vitamin K antagonist-induced bleeding, more specifically, those with intracranial hemorrhage. PCC has also been studied in trauma-induced hemorrhage; however, it remains controversial, as its potential benefits have the abilities to become flaws in this setting. 

Conclusion; Health care professionals must remain aware of the differences in products and interpret how three- versus four-factor products may affect patients, and interpret literature accordingly. The clinician must be cognizant of how to progress when treating a bleeding patient, propose a supported dosing scheme, and address the need for appropriate factor VII supplementation. At this point, PCC cannot be recommended for first-line therapy in patients with traumatic hemorrhage, and should be reserved for refractory bleeding until more data are available. 

7. A Hospitalist Goes Viral -- On Purpose  

Using satire, rap, and sometimes a Michael Jackson glove, hospitalist Zubin Damania takes his alter ego, ZDoggMD, to YouTube to sing about everything from insurance paperwork to prostate cancer.  

Tens of thousands of people have been treated by ZDoggMD – at least to a few laughs. 

Using satire, rap and sometimes, a Michael Jackson glove, hospitalist Dr. Zubin Damania takes his alter ego, ZDoggMD, to YouTube to sing about everything from insurance paperwork to prostate cancer. 

The result is hundreds of thousands of online views, and comedy that parodies pop culture (he does an excellent Yoda impersonation) and pushes some boundaries (bodily fluids are not off limits). 

"Sometimes I stop and think: Are we getting in trouble?" Damania says of the often indelicate videos he creates with coworkers and friends. "But the more we push it, the more positive the outcome." 

And when the opportunity arose, he decided to put his critique into action by heading up a new clinic in Las Vegas that he hopes will address the many drawbacks of the health system he noticed while treating seriously ill patients as a Stanford hospitalist.

For more (including 3 min YouTube video) see Kaiser Health News:  

8. Adult SBO: Evidence-based Diagnostics 

Taylor MR, et al. Acad Emerg Med. 2013;20:527–544 

Background: Small bowel obstruction (SBO) is a clinical condition that is often initially diagnosed and managed in the emergency department (ED). The high rates of potential complications that are associated with an SBO make it essential for the emergency physician (EP) to make a timely and accurate diagnosis. 

Objectives: The primary objective was to perform a systematic review and meta-analysis of the history, physical examination, and imaging modalities associated with the diagnosis of SBO. The secondary objectives were to identify the prevalence of SBO in prospective ED-based studies of adult abdominal pain and to apply Pauker and Kassirer's threshold approach to clinical decision-making to the diagnosis and management of SBO. 

Methods: MEDLINE, EMBASE, major emergency medicine (EM) textbooks, and the bibliographies of selected articles were scanned for studies that assessed one or more components of the history, physical examination, or diagnostic imaging modalities used for the diagnosis of SBO. The selected articles underwent a quality assessment by two of the authors using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Data used to compile sensitivities and specificities were obtained from these studies and a meta-analysis was performed on those that examined the same historical component, physical examination technique, or diagnostic test. Separate information on the prevalence and management of SBO was used in conjunction with the meta-analysis findings of computed tomography (CT) to determine the test and treatment threshold. 

Results: The prevalence of SBO in the ED was determined to be approximately 2% of all patients who present with abdominal pain. Having a previous history of abdominal surgery, constipation, abnormal bowel sounds, and/or abdominal distention on examination were the best history and physical examination predictors of SBO. X-ray was determined to be the least useful imaging modality for the diagnosis of SBO, with a pooled positive likelihood ratio (+LR) of 1.64 (95% confidence interval [CI] = 1.07 to 2.52). On the other hand, CT and magnetic resonance imaging (MRI) were both quite accurate in diagnosing SBO with +LRs of 3.6 (5- to 10-mm slices, 95% CI = 2.3 to 5.4) and 6.77 (95% CI = 2.13 to 21.55), respectively. Although limited to only a select number of studies, the use of ultrasound (US) was determined to be superior to all other imaging modalities, with a +LR of 14.1 (95% CI = 3.57 to 55.66) and a negative likelihood ratio (–LR) of 0.13 (95% CI = 0.08 to 0.20) for formal scans and a +LR of 9.55 (95% CI = 2.16 to 42.21) and a –LR of 0.04 (95% CI = 0.01 to 0.13) for beside scans. Using the CT results of the meta-analysis for the 5- to 10-mm slice subgroup as well as information on intravenous (IV) contrast reactions and nasogastric (NG) intubation management, the pretest probability threshold for further testing was determined to be 1.5%, and the pretest probability threshold for beginning treatment was determined to be 20.7%. 

Conclusions: The potentially useful aspects of the history and physical examination were limited to a history of abdominal surgery, constipation, and the clinical examination findings of abnormal bowel sounds and abdominal distention. CT, MRI, and US are all adequate imaging modalities to make the diagnosis of SBO. Bedside US, which can be performed by EPs, had very good diagnostic accuracy and has the potential to play a larger role in the ED diagnosis of SBO. More ED-focused research into this area will be necessary to bring about this change. 

9. High-Frequency Users of ED Care 

LaCalle EJ, et al. J Emerg Med. 2013;44:1167-1173. 

Background: The heterogeneous group of patients who frequently use the Emergency Department (ED) have been of interest in public health care reform debate, but little is known about the subgroup of the highest frequency users. 

Study Objectives: We sought to describe the demographic and utilization characteristics of patients who visit the ED 20 or more times per year. 

Methods: We retrospectively studied patients who visited a large, urban ED over a 1-year period, identifying all patients using the department 20 or more times. Age, gender, insurance, psychosocial factors, chief complaint, and visit disposition were described for all visits. Inferential tests assessed associations between demographic variables, insurance status, and admission rates. 

Results: Of the 59,172 unique patients to visit the ED between December 1, 2009 and November 30, 2010, 31 patients were identified as high-frequency ED users, contributing 1.1% of all visits. Patients were more likely to be 30–59 years of age (52%), stably insured (81%), and have at least one significant psychosocial cofactor (65%). Their admission rate was 15%, as compared to 21% for all other patients. 

Conclusions: High-frequency users are patients with significant psychiatric and social comorbidities. Given their small proportion of visits, lower admission rates, and favorable insurance status, the impact of high-frequency users of the ED may be out of proportion to common perceptions. 

10. Images in Clinical Medicine 

Bilateral Earlobe Creases

Hampton’s Hump

Scombroid Poisoning

11. New HF Guidelines 

2013 ACCF/AHA Guideline for the Management of HF: A Report of the ACC Foundation/AHA Task Force on Practice Guidelines  

Yancy CW, et al. JACC 2013 June. [Epub ahead of print] 

An update to guidelines for managing heart failure is focused on evidence-based therapy, but also highlights quality of life. 

12. A Comparison of US-guided 3-in-1 Femoral Nerve Block Versus Parenteral Opioids Alone for Analgesia in ED Patients with Hip Fractures: A RCT 

Beaudoin FL, et al. Acad Emerg Med. 2013;20:584-91.  

Objectives: The primary objective was to compare the efficacy of ultrasound (US)-guided three-in-one femoral nerve blocks to standard treatment with parenteral opioids for pain control in elderly patients with hip fractures in the emergency department (ED). 

Methods: A randomized controlled trial was conducted at a large urban academic ED over an 18-month period. A convenience sample of older adults (age ≥ 55 years) with confirmed hip fractures and moderate to severe pain (numeric rating score ≥ 5) were randomized to one of two treatment arms: US-guided three-in-one femoral nerve block plus morphine (FNB group) or standard care, consisting of placebo (sham injection) plus morphine (SC group). Intravenous (IV) morphine was prescribed and dosed at the discretion of the treating physician; physicians were advised to target a 50% reduction in pain or per-patient request. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the 11-point numerical rating scale (NRS) and calculated as the summed pain-intensity difference (SPID) over 4 hours. Secondary outcome measures included the amount of rescue analgesia and occurrence of adverse events (respiratory depression, hypotension, nausea, or vomiting). Outcome measures were compared between groups using analysis of variance for continuous variables and Fisher's exact test for categorical data.

Results: Thirty-six patients (18 in each arm) completed the study. There was no difference between treatment groups with respect to age, sex, fracture type, vital signs (baseline and at 4 hours), ED length of stay (LOS), pre-enrollment analgesia, or baseline pain intensity. In comparing pain intensity at the end of the study period, NRS scores at 4 hours were significantly lower in the FNB group (p less than 0.001). Over the 4-hour study period, patients in the FNB group experienced significantly greater overall pain relief than those in the SC group, with a median SPID of 11.0 (interquartile range [IQR] = 4.0 to 21.8) in the FNB group versus 4.0 (IQR = −2.0 to 5.8) in the SC group (p = 0.001). No patient in the SC group achieved a clinically significant reduction in pain. Moreover, patients in the SC group received significantly more IV morphine than those in the FNB group (5.0 mg, IQR = 2.0 to 8.4 mg vs. 0.0 mg, IQR = 0.0 to 1.5 mg; p = 0.028). There was no difference in adverse events between groups. 

Conclusions: Ultrasound-guided femoral nerve block as an adjunct to SC resulted in 1) significantly reduced pain intensity over 4 hours, 2) decreased amount of rescue analgesia, and 3) no appreciable difference in adverse events when compared with SC alone. Furthermore, standard pain management with parenteral opioids alone provided ineffective pain control in our study cohort of patients with severe pain from their hip fractures. Regional anesthesia has a role in the ED, and US-guided femoral nerve blocks for pain management in older adults with hip fractures should routinely be considered, particularly in cases of refractory or severe pain. 

13. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage? 

Anderson CS, et al. N Engl J Med 2013 Jun 20;368(25):2355-65. 

Background: Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. 

Methods: We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of less than 140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of less than 180 mm Hg) with the use of agents of the physician's choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups.

Results: Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively. 

Conclusions: In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure. (Funded by the National Health and Medical Research Council of Australia; INTERACT2 number, NCT00716079.) 

14. The Implications of Missed Opportunities to Diagnose Appendicitis in Children 

Naiditch JA, et al. Acad Emerg Med. 2013;20:592–596.  

Objectives: The purpose of this study was to determine the fraction of children with acute appendicitis who had recent false-negative diagnoses and to analyze the association of a missed diagnosis of appendicitis with patient outcome. 

Methods: The records of all 816 patients who underwent appendectomy for suspected appendicitis at a free-standing children's hospital between 2007 and 2010 were reviewed. A patient admitted or evaluated in the emergency department (ED), discharged without a diagnosis of appendicitis, and then readmitted with histopathologically confirmed appendicitis within 3 days was considered to have a “missed diagnosis.” Outcomes for this missed group were compared to those of the remainder of the appendectomy cohort. 

Results: Thirty-nine patients with appendicitis (4.8%) were missed at initial presentation. The most common initial discharge diagnoses were acute gastroenteritis (43.6%), constipation (10.3%), and emesis (10.3%). The median duration from the initial evaluation to the appendicitis admission was 28.3 hours (interquartile range [IQR] = 17.0 to 39.6 hours). A missed diagnosis was associated with a longer median hospitalization (5.8 days [IQR = 4.0 to 8.1 days] vs. 2.5 days [IQR = 1.8 to 4.6 days]; p less than 0.001), higher rate of perforation (74.4% vs. 29.0%; p less than 0.001), higher complication rate (28.2% vs. 10.4%; p = 0.002), and higher rate of reintervention (20.5% vs. 6.2%; p = 0.003). 

Conclusions: Of children diagnosed with appendicitis, 4.8% may have had a missed opportunity for earlier diagnosis. These false-negative diagnoses are associated with higher rates of perforation, postoperative complications, and need for postoperative interventions, as well as longer hospitalizations. 

15. Early Detection and Treatment of Patients with Severe Sepsis by Prehospital Personnel 

Guerra WF, et al. J Emerg Med. 2013;44:1116-25.  

Background: Severe sepsis is a condition with a high mortality rate, and the majority of patients are first seen by Emergency Medical Services (EMS) personnel. 

Objective: This research sought to determine the feasibility of EMS providers recognizing a severe sepsis patient, thereby resulting in better patient outcomes if standard EMS treatments for medical shock were initiated. 

Methods: We developed the Sepsis Alert Protocol that incorporates a screening tool using point-of-care venous lactate meters. If severe sepsis was identified by EMS personnel, standard medical shock therapy was initiated. A prospective cohort study was conducted for 1 year to determine if those trained EMS providers were able to identify 112 severe sepsis patients before arrival at the Emergency Department. Outcomes of the sample of severe sepsis patients were examined with a retrospective case control study. 

Results: Trained EMS providers transported 67 severe sepsis patients. They identified 32 of the 67 severe sepsis patients correctly (47.8%). Overall mortality for the sample of 112 severe sepsis patients transported by EMS was 26.7%. Mortality for the sample of severe sepsis patients for whom the Sepsis Alert Protocol was initiated was 13.6% (5 of 37), crude odds ratio for survival until discharge was 3.19 (95% CI 1.14–8.88; p = 0.040). 

Conclusions: This pilot study is the first to utilize EMS providers and venous lactate meters to identify patients in severe sepsis. Further research is needed to validate the Sepsis Alert Protocol and the potential associated decrease in mortality. 

16. Parenteral sedation of elderly patients with acute behavioral disturbance in the ED 

Calver L, et al. Amer J Emerg Med. 2013;31:970-3. 

Purposes: This study aimed to investigate sedation of elderly patients with acute behavioral disturbance (ABD) in the emergency department (ED), specifically the safety and effectiveness of droperidol. 

Basic Procedures: This was a prospective study of elderly patients (over 65 years) with ABD requiring parenteral sedation and physical restraint in the ED. Patients were treated with a standardized sedation protocol that included droperidol. Drug administration, time to sedation, additional sedation, and adverse effects were recorded. Effective sedation was defined as a drop in the sedation assessment tool score by 2 or a score of zero or less. 

Main Findings: There were 49 patients with median age of 81 years (range, 65-93 years); 33 were males. Thirty patients were given 10 mg droperidol, 15 were given 5 mg droperidol, 2 were given 2.5 mg, and 2 were given midazolam. Median time to sedation for patients receiving 10 mg droperidol was 30 minutes (interquartile range, 18-40 minutes), compared with 21 minutes (interquartile range, 10-55 minutes; P = .55) for patients receiving 5 mg droperidol. Three patients were not sedated within 120 minutes. Eighteen patients required additional sedation—10 of 30 (33%; 95% confidence interval, 18%-53%) given droperidol 10 mg compared with 7 of 15 (47%; 95% confidence interval, 22%-73%) given 5 mg. Fourteen patients required resedation. Adverse effects occurred in 5 patients (hypotension [2], oversedation [2], hypotension/oversedation [1])—2 of 30 given 10 mg droperidol and 3 of 19 not treated according to protocol. Midazolam was given initially or for additional sedation in 2 of 5 adverse effects. No patient had QT prolongation.

Principal Conclusions: Droperidol was effective for sedation in most elderly patients with ABD, and adverse effects were uncommon. An initial 5-mg dose appears prudent with the expectation that many will require another dose. 

17. How to use Paraspinous Injections for Complex Headaches 

“Who in their right mind would take an inch and a half needle, fill it with some bupivacaine, and stab somebody in the back of the neck to get rid of their headache?” 

by Taylor McCormick, MD & Stuart P. Swadron, MD on May 28, 2013 

18. The Use of CT in Pediatrics and the Associated Radiation Exposure and Estimated Cancer Risk  

Miglioretti DL, et al. JAMA Pediatr. 2013;():1-8. doi:10.1001/jamapediatrics.2013.311.  

Importance  Increased use of computed tomography (CT) in pediatrics raises concerns about cancer risk from exposure to ionizing radiation. 

Objectives  To quantify trends in the use of CT in pediatrics and the associated radiation exposure and cancer risk. 

Design  Retrospective observational study. 

Setting  Seven US health care systems. 

Participants  The use of CT was evaluated for children younger than 15 years of age from 1996 to 2010, including 4 857 736 child-years of observation. Radiation doses were calculated for 744 CT scans performed between 2001 and 2011. 

Main Outcomes and Measures  Rates of CT use, organ and effective doses, and projected lifetime attributable risks of cancer. 

Results  The use of CT doubled for children younger than 5 years of age and tripled for children 5 to 14 years of age between 1996 and 2005, remained stable between 2006 and 2007, and then began to decline. Effective doses varied from 0.03 to 69.2 mSv per scan. An effective dose of 20 mSv or higher was delivered by 14% to 25% of abdomen/pelvis scans, 6% to 14% of spine scans, and 3% to 8% of chest scans. Projected lifetime attributable risks of solid cancer were higher for younger patients and girls than for older patients and boys, and they were also higher for patients who underwent CT scans of the abdomen/pelvis or spine than for patients who underwent other types of CT scans. For girls, a radiation-induced solid cancer is projected to result from every 300 to 390 abdomen/pelvis scans, 330 to 480 chest scans, and 270 to 800 spine scans, depending on age. The risk of leukemia was highest from head scans for children younger than 5 years of age at a rate of 1.9 cases per 10 000 CT scans. Nationally, 4 million pediatric CT scans of the head, abdomen/pelvis, chest, or spine performed each year are projected to cause 4870 future cancers. Reducing the highest 25% of doses to the median might prevent 43% of these cancers. 

Conclusions and Relevance  The increased use of CT in pediatrics, combined with the wide variability in radiation doses, has resulted in many children receiving a high-dose examination. Dose-reduction strategies targeted to the highest quartile of doses could dramatically reduce the number of radiation-induced cancers. 

19. Time to Treatment with Intravenous tPA and Outcome From Acute Ischemic Stroke  

Saver JL, et al. JAMA. 2013;309(23):2480-2488.  

Importance  Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain. 

Objective  To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA. 

Design, Setting, and Patients  Data were analyzed from 58 353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012. 

Main Outcomes and Measures  Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination. 

Results  Among the 58 353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45 029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19 491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22 541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P less than .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P less than .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P less than .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P less than .001). 

Conclusions and Relevance  In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke. 

20. Increasingly Sensitive Assays for Cardiac Troponins: A Review  

de Lemos JA. JAMA. 2013;309(21):2262-2269.  

Cardiac troponins are the preferred biomarkers for diagnosis of myocardial infarction because of their high sensitivity and specificity for myocardial injury. However, acute and chronic conditions distinct from acute coronary syndromes (ACS) commonly lead to small elevations in troponin levels, with few data available regarding management of care for patients with such conditions.  

Recently developed highly sensitive troponin assays will likely lead to a substantial increase in the proportion of detectable troponin levels attributable to non-ACS conditions. Novel algorithms with highly sensitive assays, incorporating baseline troponin values and changes in values over 1 to 2 hours, may allow rapid exclusion of myocardial infarction and help to address specificity concerns but must be validated in appropriate target populations. Enhanced detection of very low troponin levels with highly sensitive assays has made feasible several potential new indications for troponin testing, including in the ambulatory setting, where assessment for low-level chronic myocardial injury may enhance risk stratification for heart failure and cardiac death. 

21. From Great Grandma to You: Epigenetic changes reach down through the generations 

By Tina Hesman Saey. Science News. March 20, 2013 

Excerpt: Susan Murphy, a researcher at Duke University, studies links between a mother’s diet and chemical exposures during pregnancy with the child’s later health. She and others have established that what happens (in the womb) can influence a child’s health for life. 

Now, animal studies and a smattering of human data suggest such prenatal effects could reach farther down the family tree: The vices, virtues, inadvertent actions and accidental exposures of a pregnant mother may pose health consequences for her grandchildren and great-grandchildren, and perhaps even their offspring. 

The resulting health effects are not produced by altering DNA itself. Rather they stem from changes in chemical tags on DNA or its associated proteins, or to actions by RNA, another type of genetic molecule. All of these are exactly the types of changes that scientists have always assumed cannot be inherited. Their very name, epigenetic, literally means “over and above” or “beyond” genetics. 

Part of your risk of disease may be determined by what your great-grandparents ate, not just the genes they passed on. One implication is that epigenetic programming becomes permanent and gets passed along to future generations. 

22. Tid Bits 

A. CDC: 1 in 5 Americans visit an ED at least once each year 

Twenty percent of Americans make at least one emergency department visit every year, with Medicaid-covered children and adults being more likely to make such visits than the privately insured or uninsured, CDC researchers said. The most common causes of ED visits between 2009 and 2010 were injuries for adults and cold symptoms for children, according to the report. 

B. Pediatric Abdominal Trauma Imaging Review 

Carlos J. Sivit, MD. Appl Radiol. 2013;42(5):8-13. 

Full-text (free with one-time registration):  

C. AAN: Don't Stop Warfarin for Dental Visits

Patients taking aspirin or warfarin (Coumadin) for prevention after a stroke don't need to stop the drug for dental procedures, the American Academy of Neurology recommended.  

Armstrong MJ, et al. Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease. Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurol 2013;80:2065-2069. 

D. Review ties high doses of some NSAIDs to heart risks 

A meta-analysis in The Lancet found high doses of some frequently used nonsteroidal anti-inflammatory drugs were associated with an elevated risk of major vascular events, primarily heart attack. However, researchers said the findings "indicate that the effects of different regimens in particular patients can be predicted, which may help physicians choosing between alternative NSAID regimens to weigh up which type of NSAID is safest in different patients." 

E. Summer Safety for Kids (Patient-friendly handout)  

Goodman DM, et al. JAMA. 2013;309(23):2505. 

F. Caffeine Withdrawal Syndrome in DSM-5: Is This For Us?
Full-text (with one-time registration):  

G.  Obesity should be considered, treated as a disease, AMA says 

In a move that could focus more attention on the condition and pave the way for better treatment and reimbursement, the American Medical Association has voted to designate obesity as a disease. A council had recommended against doing so, partly because body mass index, the usual metric for defining obesity, is flawed, but delegates overrode the recommendation. 

H. Adult Drugs Still Poisoning Children 

Burghardt LC, et al. Pediatric 2013 June 3 [Epub ahead of print] 

I. When to Get a MRI in Headache: A Review 

Michael Eller, Peter J Goadsby. Expert Rev Neurother. 2013;13(3):263-273. 

Full-text (free with one-time registration):