Monday, December 23, 2013

Lit Bits: Dec 23, 2013

From the recent medical literature...

1. Best Target Temp in Post-arrest Cooling?

Our last month’s Lit Bits (Nov 30) opened with a summary of the Nielsen N et al. study “Targeted temperature management at 33°C versus 36°C after cardiac arrest, N Engl J Med 2013 Nov 17.

How might one interpret this in light of prior research on the topic? Here’s a helpful 12-minute commentary from U Penn.

2. Ondansetron and the Risk of Cardiac Arrhythmias: A Systematic Review and Postmarketing Analysis

Freedman SB, et al. Ann Emerg Med. 2013 Dec 4 [Epub ahead of print]

Study objective: To explore the risk of cardiac arrhythmias associated with ondansetron administration in the context of recent recommendations for identification of high-risk individuals.

Methods: We conducted a postmarketing analysis and systematically reviewed the published literature, grey literature, manufacturer’s database, Food and Drug Administration Adverse Events Reporting System, and the World Health Organization Individual Safety Case Reports Database (VigiBase). Eligible cases described a documented (or perceived) arrhythmia within 24 hours of ondansetron administration. The primary outcome was arrhythmia occurrence temporally associated with the administration of a single, oral ondansetron dose. Secondary objectives included identifying all cases associating ondansetron administration (any dose, frequency, or route) to an arrhythmia.

Results: Primary: No reports describing an arrhythmia associated with single oral ondansetron dose administration were identified. Secondary: Sixty unique reports were identified. Route of administration was predominantly intravenous (80%). A significant medical history (67%) or concomitant use of a QT-prolonging medication (67%) was identified in 83% of reports. Approximately one third occurred in patients receiving chemotherapeutic agents, many of which are known to prolong the QT interval. An additional third involved administration to prevent postoperative vomiting.

Conclusion: Current evidence does not support routine ECG and electrolyte screening before single oral ondansetron dose administration to individuals without known risk factors. Screening should be targeted to high-risk patients and those receiving ondansetron intravenously.

3. Quality Measurement in the ED: Past and Future

Schuur JD, et al. Health Aff 2013;32:2129-2138.

As the United States seeks to improve the value of health care, there is an urgent need to develop quality measurement for emergency departments (EDs). EDs provide 130 million patient visits per year and are involved in half of all hospital admissions. Efforts to measure ED quality are in their infancy, focusing on a small set of conditions and timeliness measures, such as waiting times and length-of-stay.

We review the history of ED quality measurement, identify policy levers for implementing performance measures, and propose a measurement agenda. Initial priorities include measures of effective care for serious conditions that are commonly seen in EDs, such as trauma; measures of efficient use of resources, such as high-cost imaging and hospital admission; and measures of diagnostic accuracy. More research is needed to support the development of measures of care coordination and regionalization and the episode cost of ED care. Policy makers can advance quality improvement in ED care by asking ED researchers and organizations to accelerate the development of quality measures of ED care and incorporating the measures into programs that publicly report on quality of care and incentive-based payment systems.

4. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with AF: a meta-analysis of randomized trials

Ruff CT, et al. The Lancet 4 December 2013 [Epub ahead of print]

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes.

We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71 683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF—TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity.

42 411 participants received a new oral anticoagulant and 29 272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73—0·91; p less than 0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38—0·64; p less than 0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85—0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39—0·59; p less than 0·0001), but increased gastrointestinal bleeding (1·25, 1·01—1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59—0·81 vs 0·93, 0·76—1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84—1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43—1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02—1·60; p=0·045).

This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk—benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.

5. Prehospital Shocks: Be Quick!

Shorter pre- and peri-shock pauses were associated with greater survival from out-of-hospital cardiac arrest.

Cheskes S, et al. Resuscitation 2013 Oct 28. [Epub ahead of print]

Previous research has demonstrated significant relationships between peri-shock pause and survival to discharge from out-of-hospital shockable cardiac arrest (OHCA).

To determine the impact of peri-shock pause on survival from OHCA during the ROC PRIMED randomized controlled trial.

We included patients in the ROC PRIMED trial who suffered OHCA between June 2007 and November 2009, presented with a shockable rhythm and had CPR process data for at least one shock. We used multivariable logistic regression to determine the association between peri-shock pause duration and survival to hospital discharge.

Among 2006 patients studied, the median (IQR) shock pause duration was: pre-shock pause 15s (8, 22); post-shock pause 6s (4, 9); and peri-shock pause 22.0s (14, 31). After adjusting for Utstein predictors of survival as well as CPR quality measures, the odds of survival to hospital discharge were significantly higher for patients with pre-shock pause less than 10s (OR: 1.52, 95% CI: 1.09, 2.11) and peri-shock pause less than 20s (OR: 1.82, 95% CI: 1.17, 2.85) when compared to patients with pre-shock pause ≥20s and peri-shock pause ≥40s. Post-shock pause was not significantly associated with survival to hospital discharge. Results for neurologically intact survival (Modified Rankin Score≤3) were similar to our primary outcome.

In patients with cardiac arrest presenting in a shockable rhythm during the ROC PRIMED trial, shorter pre- and peri-shock pauses were significantly associated with higher odds of survival. Future cardiopulmonary education and technology should focus on minimizing all peri-shock pauses.

6. BMJ’s (comical) Christmas Issue

A. Like a virgin (mother): analysis of data from a longitudinal, US population representative sample survey

Herring AH, et al. BMJ 2013;347:f7102

Conclusions: Around 0.5% of women consistently affirmed their status as virgins and did not use assisted reproductive technology, yet reported virgin births. Even with numerous enhancements and safeguards to optimize reporting accuracy, researchers may still face challenges in the collection and analysis of self-reported data on potentially sensitive topics.

B. Following celebrities’ medical advice: meta-narrative analysis

Hoffman SJ, et al. BMJ 2013;347:f7151

Introduction: Celebrities frequently give medical advice and people often follow it. Whether motivated by good intentions or financial rewards, celebrities can generate much publicity for health campaigns by virtue of their visibility, public interest, and perceived newsworthiness. When journalist Katie Couric televised her colonoscopy on NBC’s Today Show in 2000, colorectal cancer screenings by 400 American endoscopists increased by 21% the next month.1 Following actor-singer Kylie Minogue’s diagnosis of breast cancer, bookings for mammograms rose by 40% in four Australian states.2 Twice as many screenings for cervical cancer were conducted in England during March 2009 compared with the same month one year earlier, corresponding to reality TV star Jade Goody’s death from the disease.3

The pros and cons of celebrity health advice: Many celebrities have mobilised their influence for good. Actor Michael J Fox’s foundation has raised over $350m (£215m; €260m) for research into Parkinson’s disease,4 whereas singer Sir Elton John’s charity has raised more than $300m towards research into HIV/AIDS.5 But the messages espoused by celebrities can also conflict with those recommended by health professionals, public health authorities, and the best available research  evidence. British television presenter Sir Michael Parkinson promoted an unsupported self diagnosis technique for prostate cancer based on his own experiences: “The test is if you can pee against a wall from two feet, you haven’t got it.”6 Having breast cancer at age 36, actor Christina Applegate promoted magnetic resonance imaging for early detection; yet the US National Cancer Institute does not endorse such investigations for those at average risk of breast cancer.7 Actor Suzanne Somers advocates her own brand of medicine, including bioidentical hormones to reverse aging and proteolytic enzyme therapy for pancreatic cancer, despite her therapies lacking evidence of effectiveness…8 9

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

C. Barcelona baby boom: does sporting success affect birth rate?

Montesinos J, et al.  BMJ 2013;347:f7387

Introduction: On 6 May 2009, Andrés Iniesta scored a last minute goal against Chelsea FC, which put Football Club Barcelona (popularly known as Barça) in the UEFA Champions League final. This single goal was so emotive that the skies over Catalonia reverberated with fireworks, shouts of joy, and the banging of pots and pans. According to some media reports, many fans also celebrated by making other kinds of noise. Nine months after the event, Catalonia’s COMRadio broadcast the results of an informal survey of five hospitals, which reported a 45% increase in the number of births.1 2 3 The putative cause of this spike in natality was Iniesta’s breathtaking goal, and the children born during this boom came to be known popularly as “the Iniesta generation,” implying that Iniesta had fathered—through surrogates—hundreds or even thousands of babies (fig 1).

Similar claims made by the media in the past have been disproved under scrutiny.4 5 6 7 For example, the 1965 blackout in the northeast United States affected over 30 million people, including four million homes in New York City. Nine months after this event, the New York Times published four consecutive articles reporting a 30% increase in the birth rates of five hospitals in Manhattan.8 However, in 1970, Menaker et al6 showed that there had actually been a 20-25% decline in births rather than an increase. Nevertheless, some seasonal and social effects appear to be certain. We hope, for example, that it is not too late for the readers of this issue to bear in mind the “Christmas effect,” in which a sharp September spike appears nine months after the December holidays.9

We wondered if the Iniesta effect in Catalonia was real, and, if so, whether the exhilaration associated with football or other sporting events can truly have profound demographic repercussions…

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

D. Were James Bond’s drinks shaken because of alcohol induced tremor?

Johnson G, et al. BMJ 2013;347:f7255

Objective To quantify James Bond’s consumption of alcohol as detailed in the series of novels by Ian Fleming.

Design Retrospective literature review.

Setting The study authors’ homes, in a comfy chair.

Participants Commander James Bond, 007; Mr Ian Lancaster Fleming.

Main outcome measures Weekly alcohol consumption by Commander Bond.

Methods All 14 James Bond books were read by two of the authors. Contemporaneous notes were taken detailing every alcoholic drink taken. Predefined alcohol unit levels were used to calculate consumption. Days when Bond was unable to consume alcohol (such as through incarceration) were noted.

Results After exclusion of days when Bond was unable to drink, his weekly alcohol consumption was 92 units a week, over four times the recommended amount. His maximum daily consumption was 49.8 units. He had only 12.5 alcohol free days out of 87.5 days on which he was able to drink.

Conclusions James Bond’s level of alcohol intake puts him at high risk of multiple alcohol related diseases and an early death. The level of functioning as displayed in the books is inconsistent with the physical, mental, and indeed sexual functioning expected from someone drinking this much alcohol. We advise an immediate referral for further assessment and treatment, a reduction in alcohol consumption to safe levels, and suspect that the famous catchphrase “shaken, not stirred” could be because of alcohol induced tremor affecting his hands.

E. Being right or being happy: pilot study

Arroll B, et al. BMJ 2013;347:f7398

Intervention: The intervention was for the male to agree with his wife’s every opinion and request without complaint. Even if he believed the female participant was wrong, the male was to bow and scrape…

Discussion: The results of this trial show that the availability of unbridled power adversely affects the quality of life of those on the receiving end.

Strengths and weaknesses: The study has some limitations. There was no trial registration, no ethics committee approval, no informed consent, no proper randomisation, no validated test instrument, and questionable statistical assessment. We used the eyeball technique for single patient trials which, as Sackett says, “more closely matches the way we think as clinicians.”3

Generalisability: Many people in the world live as couples, and we believe that it could be harmful for one partner to always have to agree with the other. However, more research is needed to see whether our results hold if it is the male who is always right.

F. The Brady[cardia] Bunch? New evidence for nominative determinism in patients’ health: retrospective, population based cohort study

Keaney JJ, et al. BMJ 2013;347:f6627

Objective To ascertain whether a name can influence a person’s health, by assessing whether people with the surname “Brady” have an increased prevalence of bradycardia.

Design Retrospective, population based cohort study.

Setting One university teaching hospital in Dublin, Ireland.

Participants People with the surname “Brady” in Dublin, determined through use of an online telephone directory.

Main outcome measure Prevalence of participants who had pacemakers inserted for bradycardia between 1 January 2007 and 28 February 2013.

Results 579 (0.36%) of 161 967 people who were listed on the Dublin telephone listings had the surname “Brady.” The proportion of pacemaker recipients was significantly higher among Bradys (n=8, 1.38%) than among non-Bradys (n=991, 0.61%; P=0.03). The unadjusted odds ratio (95% confidence interval) for pacemaker implantation among individuals with the surname Brady compared with individuals with other surnames was 2.27 (1.13 to 4.57).

Conclusions Patients named Brady are at increased risk of needing pacemaker implantation compared with the general population. This finding shows a potential role for nominative determinism in health.

7. Imaging in the NEXUS-negative patient: when we break the rule

Morrison J, et al. Amer J Emerg Med. 2014;32:67-70

Background: In spite of general acceptance and validation of NEXUS (National Emergency X-Radiography Utilization Study) in the clearance of cervical spine (C-spine) immobilized patients, clinicians often elect to image NEXUS-negative patients in clinical practice.

Objectives: We sought to determine which variables (patient age, mechanism of injury, provider level of training, provider self-reported motivation) contribute to the decision of emergency medicine providers to image NEXUS-negative patients.

Methods: This is a prospective observational study of patients with blunt trauma and risk for C-spine injury who did not meet “trauma team activation” criteria. Providers at one high-volume emergency department (ED) prospectively recorded NEXUS criteria, as well as rationale for imaging NEXUS-negative patients. Researchers then retrospectively queried the electronic medical record for patient age, mechanism of injury, and results of diagnostic imaging. Study data were analyzed with χ2 and descriptive statistics.

Results: Three hundred patients were enrolled; 169 patients received C-spine imaging, of whom 53 were NEXUS-negative. There was no difference in imaging of NEXUS-negative patients as a factor of medical provider level of training (P=0.42). Of NEXUS-negative patients receiving imaging, 51 (96%) were older than 65 years, and 52 were being evaluated for a fall on level ground. Imaging revealed 7 positive findings. Two of these injuries were in NEXUS-negative patients.

Conclusion: Regardless of level of training, providers in our ED often imaged patients who met NEXUS low-risk criteria. This was mot common in geriatric patients who presented after falls. This digression from NEXUS led to the diagnosis of significant injuries in 2 patients which would otherwise have been missed.

8. Bacteremia in Febrile Infants in the U.S.

E. coli was the most commonly identified cause of bacteremia in infants younger than 90 days.

Approximately 2% of febrile infants have bacteremia and the most common causes in the U.S. are Group B Streptococcus (GBS), Escherichia coli, and Listeria monocytogenes. However, recent studies limited to a single geographic area have demonstrated declining rates of infections with GBS and the majority of infections in this age group attributable to E. coli. To examine more diverse trends, investigators retrospectively evaluated positive blood cultures from previously healthy febrile infants admitted to general pediatric units in six different geographic regions in the U.S. between 2006 and 2012.

Of 181 positive cultures, 19 different species were isolated from 177 patients. E. coli was the most commonly isolated pathogen (42%), followed by GBS (23%), S. pneumoniae (6%), and S. aureus (5%). More than 90% of infants with E. coli bacteremia had concurrent E. coli urinary tract infection, and 27% of infants with GBS bacteremia had meningitis. Infants with S. pneumoniae bacteremia were older than the entire group (median age, 66 vs. 34 days). No positive blood cultures for L. monocytogenes were identified, prompting the authors to question empiric antibiotic coverage for this organism.

Comment: This study confirms the importance of E. coli as a neonatal pathogen causing bacteremia in febrile infants, particularly when associated with urinary tract infection. The authors question the continued need for empiric L. monocytogenes coverage with ampicillin, however, this study excluded infants admitted to neonatal intensive care units, likely excluding early-onset cases. More data are needed before any change in empiric antibiotic coverage for infants is indicated.

Deborah Lehman, MD, Journal Watch Emerg Med, December 10, 2013.

Reference: Biondi E et al. Epidemiology of bacteremia in febrile infants in the United States. Pediatrics 2013 Dec; 132:990.

9. An Unusual Case of Abdominal Pain: An Interactive Case from the NEJM

Goodman R, et al. N Engl J Med 2013; 369:e34

A 41-year-old man presented to the emergency department with abdominal pain. He described the pain as the most excruciating he had ever had. It developed suddenly, without warning, 1 hour before presentation. The pain was located in the right lower quadrant and radiated to his right flank and groin. It was slightly alleviated when he was lying supine. He reported nausea and one episode of nonbloody, nonbilious emesis shortly after the onset of pain.

The patient reported having a less severe episode of similar pain 2 weeks earlier in the left lower quadrant that radiated to his left flank…

10. Risk of intracranial injury after minor head trauma in patients with pre-injury use of clopidogrel

Levine M, et al. Amer J Emerg Med. 2014;32:71-74.

Background: Clopidogrel is an adenosine diphosphate receptor antagonist. The risk of intracranial hemorrhage following minor head trauma in patients with pre-injury use of clopidogrel has not been fully determined.

Methods: This case-controlled study examined the effects of pre-injury use of clopidogrel in adult (age 14 years and older) patients with minor head trauma.

Results: During the study period, 1660 patients head computed tomography scans were performed in the emergency department, of which 658 met inclusion criteria. Intracranial hemorrhage was noted in 30% of patients on clopidogrel, compared with 2.2% of those patients without pre-injury use of clopidogrel. After performing a logistic regression analysis for confounders, the pre-injury use of clopidogrel was significantly associated with intracranial hemorrhage in this study population (OR 16.7; 95% CI 1.71-162.7).

Conclusion: The use of clopidogrel is associated with a significantly increased risk of developing intracranial hemorrhage following minor trauma.

11. Images in Clinical Practice

Evolution of a Diabetic Foot Infection 

Spinal Fracture and a Widened Interspinous Gap 

Beans and Beaks

Lingual Squamous-Cell Carcinoma

Man With Air Below the Right Diaphragm

A Healthy Young Man with Neck Sprain

12. Readmissions Research

A. Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study

Donze J, et al. BMJ 2013;347:f7171

Objective To evaluate the primary diagnoses and patterns of 30 day readmissions and potentially avoidable readmissions in medical patients with each of the most common comorbidities.

Design Retrospective cohort study.

Setting Academic tertiary medical centre in Boston, 2009-10.

Participants 10 731 consecutive adult discharges from a medical department.

Main outcome measures Primary readmission diagnoses of readmissions within 30 days of discharge and potentially avoidable 30 day readmissions to the index hospital or two other hospitals in its network.

Results Among 10 731 discharges, 2398 (22.3%) were followed by a 30 day readmission, of which 858 (8.0%) were identified as potentially avoidable. Overall, infection, neoplasm, heart failure, gastrointestinal disorder, and liver disorder were the most frequent primary diagnoses of potentially avoidable readmissions. Almost all of the top five diagnoses of potentially avoidable readmissions for each comorbidity were possible direct or indirect complications of that comorbidity. In patients with a comorbidity of heart failure, diabetes, ischemic heart disease, atrial fibrillation, or chronic kidney disease, the most common diagnosis of potentially avoidable readmission was acute heart failure. Patients with neoplasm, heart failure, and chronic kidney disease had a higher risk of potentially avoidable readmissions than did those without those comorbidities.

Conclusions The five most common primary diagnoses of potentially avoidable readmissions were usually possible complications of an underlying comorbidity. Post-discharge care should focus attention not just on the primary index admission diagnosis but also on the comorbidities patients have.

B. Hospitalists may help lower readmission rates

Having hospitalists present at hospitals was associated with reduced 30-day readmission rates for heart failure, heart attack and pneumonia, according to a report in The Journal of Hospital Medicine. However, researchers found no link between the presence of hospitalists and differential mortality rates.

13.   Can It Be True? EHRs Make EPs' Lives Better

Ballard D. Emerg Med News. 2013;35(11A).

As a kid, I watched my mother go through a weekend bill-paying ritual. She would sort through a large and sometimes teetering stack of mail, setting aside certain envelopes. Then she would pull out her checkbook, a bulky, Costanza-like item, and initiate scribbling. Writing checks, addressing envelopes, licking stamps, and balancing numbers on her ledger. It was quite a production, though it seems quite archaic to those of us who use online banking.

Bills come by email, and are paid with a click or two— no checkbook, no stamps, no hassle. Other bills are paid automatically each month, an innovation so simple that the danger is that you might lose track of who you are paying and why. To me, and to others, I suspect, this represents technology at its best, making our lives easier so we can focus on more worthwhile endeavors (e.g., fantasy football waiver wire pickups). Other examples of such sublime simplicity are GPS navigation, online flight check-in, and certain (but not all) smartphones.

But for every divine invention, there is an example of technology gone awry, technology that makes lives complicated and aggrieved, such as iTunes upgrades, the remote control for my ceiling fan, and until recently, the electronic health record (EHR).

EHRs have received considerable press, and most certainly hold the promise to make our lives simpler and healthier. But they have not yet clearly delivered on their promise despite their central role in the federal health care overhaul and the billions spent on them. They are expensive and they glitch, and they can be clunky chains that shackle health care providers to their computers at the expense of face-to-face time with patients. Take, for example, the recent study entitled “4000 Clicks: A Productivity Analysis of Electronic Medical Records in a Community Hospital ED,” which precisely documented the secretarial nature of an EP's job in the current EHR era. (Am J Emerg Med 2013 Sep 20.) Hill and colleagues observed that EPs at a community ED with an EHR spent a whopping 43 percent of their time on data entry (orders and charting). Well, maybe not so whopping; there are some shifts where it feels like I barely look up from my keyboard long enough to realize it is time to go home.

I'll readily admit that I've suffered from click fatigue as I navigate through the process of computer-based patient care, often bombarded by excess information that is redundant or irrelevant. Nonetheless, EHR technology has improved vastly over the past few years, and it will not be long until the paper medical chart has joined relics of the Jurassic era. Like it or not, medicine is going electronic. The question is, however, will EHRs, like online banking, improve the quality of our lives? Up until now, the evidence of the benefits of the EHR — to patients and providers — has been mixed. That, however, is starting to change.

A recent JAMA study by Mary Reed, DrPH, and colleagues (including me, by way of full disclosure) adds to a growing body of evidence supporting the beneficial effects of EHR implementation. We examined the staggered implementation of the EHR across Kaiser in Northern California between 2005 and 2008, and compared “negative” outcomes such as visits to the ED and hospitalizations in 169,000 diabetic patients whose care was administered through either an EHR or a traditional paper chart. The study found that annual ED visits declined 5.5 percent, and annual hospitalizations declined 5.2 percent. There was no significant change in the number of doctor's office visits for patients with diabetes before or after the EHR was implemented. (2013;310[10]:1060.)

“Since our study finds EHR-related improvement in care quality and outcomes without changes in office visit rates, this may reflect greater efficiency during visits or care delivery between visits,” Dr. Reed wrote.

These results are promising, but must be considered cautiously. Any study that looks back in time and attempts to discern which medical interventions were associated with improvements in patient health is subject to confounding, such that the findings could also have been affected by other factors. The confounders in this study were minimized (but not necessarily eliminated) by looking at an intervention (the EHR) that was implemented in a staggered fashion over a number of years and by using statistical correction that included fixed effects estimation and running multiple sensitivity analyses. We can be reasonably confident that the results of the study demonstrate a real benefit to patients, but we must also recognize that the actual magnitude of that benefit is difficult to estimate and may not be all that profound. And, of course, this study just scratches the surface of the issue of cost and time-effectiveness.

Nonetheless, this is a promising study that brings me pleasant visions of the future of the EHR, visions of a time when medical care across all venues and hospital systems can be seamlessly integrated and provide real-time feedback to patients and clinicians, a time when the EHR only asks me to click through alerts that actually matter and to when the screen itself presents a pleasant and intuitive interface. (See photo caption.) To a time when the individual variations in patient characteristics, even down to their genetic sequences, can help generate automatic recommendations about treatments and prevention strategies. A time when patients can be active participants in their own record, helping to verify and augment their information and use the tools of the EHR to make shared decisions with their doctor effectively.

Much work must still be done, but it seems to me the EHR has now turned the corner and that we can be confident that it will continue to evolve into a technological tool that will make our lives easier, better, and healthier. 

14. Shorter Course of Acetylcysteine Treatment for Acetaminophen Overdose Is Better Tolerated

Kristi L. Koenig, MD, Journal Watch Emergency Medicine 

A 12-hour regimen was associated with less vomiting and fewer anaphylactoid reactions than the standard 20- to 25-hour protocol.

Acetaminophen overdose is one of the few toxicological emergencies with a specific antidote; however, acetylcysteine administration regimens can be complicated, time-consuming, and costly. In a randomized, double-blind study at 3 U.K. hospitals, 222 patients who presented within 8 hours of acute acetaminophen overdose received either the standard U.K. acetylcysteine treatment regimen or a shorter, modified regimen (see Table). In addition, patients were randomized to pretreatment with ondansetron or placebo.

Vomiting, retching, or need for rescue antiemetics within 2 hours after initiation of acetylcysteine was less frequent in patients randomized to the shorter regimen (36% vs. 65%; adjusted odds ratio, 0.26) and in those randomized to ondansetron (41% vs. 63%; adjusted OR, 0.41). Anaphylactoid reactions occurred in 28% of those in the standard-treatment group, but only 5% of those in the shorter-regimen group. The proportion of patients with a 50% increase in alanine aminotransferase activity did not differ between acetylcysteine-regimen groups, but was higher in ondansetron recipients than placebo recipients.

Comment: This well-designed study performed in the U.K., where acetaminophen overdose is more common than in the U.S., provides strong evidence that an abbreviated, 12-hour acetylcysteine regimen is better tolerated and has fewer side effects than currently recommended regimens. We may soon see a reduction in treatment times to the point that we can fully manage acetaminophen-overdose patients in emergency department observation units, thereby decreasing hospital admissions.

Source: Bateman DN et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: A randomised controlled trial. Lancet 2013 Nov 28 [E-pub ahead of print].

15. Ann Emerg Med Lit Reviews and Summaries

A. Is Intravenous Acetylcysteine More Effective Than Oral Administration for the Prevention of Hepatotoxicity in Acetaminophen Overdose?

Schwarz E. Ann Emerg Med. 2014;63:79-80.

Take-home message: Rates of hepatotoxicity from acetaminophen appear to be similar whether acetylcysteine is administered orally or intravenously.

B. Can We Safely Discharge Low-Risk Patients With Febrile Neutropenia From the Emergency Department?

Mamtani M, et al. Ann Emerg Med. 2014;63:48-51.

Bottom Line: According to the available evidence, treatment outcomes of low-risk febrile neutropenic patients in the inpatient and outpatient setting are comparable. An expert consensus panel from the American Society of Clinical Oncology stated that, although evidence is incomplete, carefully selected low-risk patients may be treated in the outpatient setting.8 The next step is to determine a low-risk group that can be safely treated in the outpatient setting. The expert consensus panel recommends the MASCC score in conjunction with their criteria as the best method for determining risk status.

According to the available evidence, of the patients who are discharged, there is a 17% to 21% rate of admission for failing outpatient treatment.2, 3, 4 The mortality rate for these patients is variable and ranges from 0% to 4%.2, 3, 4 Because all 3 articles had different definitions of what constitutes low risk, the variable outcomes are not unexpected. This series of articles highlights the importance of carefully selecting low-risk patients for discharge. Elting et al4 showed no deaths in their low-risk febrile neutropenic patients; a risk designation based on their criteria (Table) with excellent outpatient follow-up and currently accepted oral antibiotic treatment may be an effective model to follow for future studies.

It is reasonable to discharge low-risk febrile neutropenic patients home from the ED with oral antibiotics and close outpatient follow-up.

C. Are Antibiotics Required for the Treatment of Uncomplicated Diverticulitis?

Smolarz CM, et al. Ann Emerg Med. 2014;63:52-53.

Take-home message: Limited data (1 randomized trial) suggest that antibiotics may be no better than placebo for the treatment of uncomplicated diverticulitis. More randomized trial data are required to help define the best therapeutic option.

D. Should Neuraminidase Inhibitors Be Prescribed for Patients With Influenza?

Patel DM, et al. Ann Emerg Med. 2014;63:54-55.

Take-home message: Patients who received neuraminidase inhibitors for acute influenza within 48 hours of symptom onset began to have symptom resolution approximately 1 day sooner compared with those who received placebo.

E. The Surviving Sepsis Campaign Guidelines 2012: Update for Emergency Physicians

Jones AE, et al. Ann Emerg Med. 2014;63:35-47.

Abstract: The Surviving Sepsis Campaign recently developed and published an updated version in 2012 of the international guidelines for the assessment and management of severe sepsis and septic shock. These guidelines reflect literature published in the last 5 years, and many of the recommendations have direct implications for emergency physicians. In this review, we present a concise summary of these recommendations, with a particular focus on those that have changed and those that have direct relevance to the clinical practice of emergency medicine.

F. Does Ultrasonographic Imaging Reduce the Risk of Failed Lumbar Puncture?

Swaminathan A, et al. Ann Emerg Med. 2014;63:33-34.

Take-home message: In adults, ultrasonographic guidance for lumbar puncture reduces the risk of failure and traumatic procedures.

16. Jolt accentuation of HA and other clinical signs: poor predictors of meningitis in adults

Nakao JH, et al. Amer J Emerg Med. 2014;32:24-28

Jolt accentuation or exacerbation of a baseline headache with horizontal rotation of the neck is a physical finding believed to assess for meningeal irritation. We conducted a prospective observational study of neurologically intact emergency department (ED) patients undergoing lumbar puncture in 2 inner city academic EDs to validate the sensitivity and specificity of jolt accentuation and to assess the sensitivity and specificity of Kernig sign, Brudzinski sign, and nuchal rigidity, in predicting cerebrospinal fluid (CSF) pleocytosis in individuals being assessed for meningitis.

Adult patients 18 years and older undergoing lumbar puncture between 2006 and 2009 were approached for consent. Exclusions included inability to consent and altered mental status. Physicians were asked to answer a questionnaire of physical examination findings before receiving CSF results. The primary outcome was the presence or absence of pleocytosis, defined as greater than or equal to 5 cells/high-power field in the fourth CSF tube. We calculated descriptive statistics and tests of diagnostic accuracy.

A total of 230 patients consented for participation and had CSF white blood cell counts recorded. Forty-seven individuals (20%) had pleocytosis. A total of 197 patients had headache and were, hence, eligible for jolt accentuation assessment. For pleocytosis, the sensitivity of jolt accentuation was 21%, Kernig sign was 2%, Brudzinski sign was 2%, and nuchal rigidity was 13%. The specificity of jolt accentuation was 82%, Kernig sign was 97%, Brudzinski sign was 98%, and nuchal rigidity was 80%.

Jolt accentuation in our cohort was poorly predictive of pleocytosis and insensitive. The presence of Kernig sign, Brudzinski sign, or nuchal rigidity has moderate positive but no negative predictive value for pleocytosis.

17. Emergency Medicine: Observation Saves $$$

By Cole Petrochko, Staff Writer, MedPage Today, Dec 3, 2013

Action Points
  • ·         Note that this analysis of Georgia and national data suggest that dedicated, emergency department-based observation units may dramatically cut the costs of treating certain common conditions such as heart failure.
  • ·         Be aware that some of the cost savings may represent cost shifting, as patient copays may be higher when under "observation" status.

Keeping selected patients under observation in a dedicated hospital unit with defined protocols could yield hundreds of millions of dollars in cost savings, researchers found.

Compared with patients who were observed in other areas of the hospital, those who received observation in a unit dedicated to the practice and with clear, condition-specific protocols had a total length of stay that was 23% to 38% shorter, a 17% to 44% lower likelihood of full inpatient admission, and were associated with an estimated $950 million in potential saved costs nationally, according to Michael Ross, MD, of Emory University in Atlanta, and colleagues.

In addition, an estimated 11.7% of short-stay emergency department inpatients (EDs) could receive treatment in these type I observation units nationally, which would be associated with cost savings of $5.5 to $8.5 billion, they wrote online in the emergency care-focused December issue of Health Affairs.

A similar strategy was proposed in a Journal of the American College of Cardiology in January 2013 for heart failure patients, in which the authors looked at ways to distinguish high-risk patients from others, and then at how to determine which patients were responsive to treatment, in order to decide whom to admit to the emergency department.

The "kept for observation" status has been a topic of controversy for Medicare patients for years, and in 2012 an investigation by the Department of Health and Human Services Inspector General found inconsistency between hospitals in how they determined whether a patient was admitted or kept under observation. For Medicare patients, such "observation stays" are also associated with higher out-of-pocket costs and a lower likelihood that nursing home expenses will be covered.

In the current study, the authors conducted a cost analysis using 2010 data from three sources: observation units at three Atlanta hospitals, statewide discharge data from Georgia, and national survey and discharge data.

The authors looked at four types of observational units:
  • ·         Type I, which was protocol-driven and had care generally directed by the emergency department
  • ·         Type II, which offered discretionary care, had care directed by a variety of specialists, and was based in the emergency department
  • ·         Type III, which was protocol-driven, had beds located anywhere in the hospital, and was known as a "virtual observation unit"
  • ·         Type IV, which offered discretionary care, had beds anywhere in the hospital, and was the most common type of observation conducted, but care was not structured and patients' needs were not well-aligned with resources 

The authors looked at patients in type 1 observation units in the Atlanta hospitals and compared them with patients in all four types of observation units included in the statewide and national data.

They noted that type I observation units "include a dedicated unit, operational guidelines, condition-specific protocols, appropriate staffing and administrative oversight, ancillary services support, and close attention to metrics of use and quality." The patients who attend these units were selected through established guidelines, as was the treatment they received and the conditions under which they were discharged.

Common conditions for those placed under observation nationally included abdominal pain, chest pain, fluid and electrolyte disorders, cardiac dysrhythmias, and lower respiratory disease. Data from Emory and Atlanta showed chest pain and syncope were the two most common conditions that resulted in patients being held under observation.

Compared with type I units in the three centers in Atlanta, patients admitted to Georgia or national general observational units had longer lengths of stay and higher rates of inpatient admission (13.1% versus 15.8% and 32.2%, respectively). Also, fewer than 0.1% of patients in type I observation units had stays longer than 2 days versus 7.2% of those in Georgia and 6.9% nationally. The authors said data from the Atlanta units "was consistent with performance of type I units reported in previous studies and national surveys."

To measure cost savings associated with these differences, the researchers used discharge data from the Nationwide Inpatient Sample, including charges for hospitalizations.

Estimates of admissions eligible for observation status were established through measuring the number of emergency department admissions that resulted in inpatient stays of 2 or fewer days. Admissions eligible for an observation unit accounted for 11.7% of all admissions nationally to an emergency department, and totaled $20.2 billion in cost.

The authors noted that the savings associated with use of a type I observation unit compared with traditional inpatient care "have been reported to be in the range of 27% to 42%," which would shave $5.5 to $8.5 billion off of expenditures on emergency department services in the U.S.

They added that, for many patients, "type I units are a more cost-effective and efficient use of hospital-based healthcare resources than inpatient admissions." However, some two-thirds of U.S. hospitals would require an organizational overhaul since they currently do not have an observational treatment-specific unit. To reward creation of such units, payers would need to develop reimbursement schemes which would pay hospitals more for type 1 observation unit patient care "than for care provided in any inpatient bed," they wrote.

18. Study Dispels 'Urban Legends' About Frequent ED Users

Miriam E. Tucker, Medscape Medical News, December 04, 2013

Washington, DC — Contrary to "urban legend," frequent users of emergency care actually have high rates of primary care use and only a small proportion of their emergency department (ED) visits are for substance abuse and mental health problems, a new study of Medicaid ED users in New York City shows.

The results of the study, involving administrative data for more than 200,000 Medicaid beneficiaries, counters the notion that frequent users of ED services are people who try to avoid visiting primary care physicians who could treat their conditions more easily and less expensively. Moreover, the study also found that visits for substance abuse and mental health comprised just 5% of total visits in a single year.

"We found that a lot of the tenets that underlie the urban legend of frequent ED use are unfounded," Maria C. Raven, MD, assistant professor in the Department of Emergency Medicine at the University of California, Los Angeles, said at a briefing here sponsored by the journal Health Affairs. The study was among several published in the journal's December theme issue, devoted to the future of emergency medicine.

The study findings point to the need for better care coordination, Dr. Raven told Medscape Medical News.

"Placing all the burden on primary physicians to decrease this [ED] use might be unrealistic because these patients are really sick...I think we need better care coordination programs in place, and we need to provide [primary care providers] with more resources. In the current 15-minute visit it's probably very difficult to address all the needs of these complex patients," she said.

Lemeneh Tefera, MD, an emergency physician who was not involved in the research, told Medscape Medical News that the study findings also serve to dispel the concern that the expansion of Medicaid under the Affordable Care Act (ACA) will create an exceptionally onerous burden on EDs.

"I think the ED is already being used excessively by multiple types of patient populations, so the uninsured are not the sole reason that EDs are busy. In fact, the very well insured use the ED for different reasons that also impact crowding and overutilization," said Dr. Tefera, adjunct associate professor of Health Policy and Health Economics in the Department of Emergency Medicine at George Washington School of Medicine, Washington, DC.

Who's Using the ED? 
The investigators analyzed Medicaid claims data for a total of 212,259 patients aged 18 to 62 years in New York City, including an "index visit" to the ED in 2007 and claims data for 3 years prior and 3 years after that visit. They found that ED use contributed to just 2.1% of overall Medicaid spending. Even the "ultra-high" ED users, with 15 or more visits per year, contributed just 4.6% to total costs, Dr. Raven reported.

Half of all ED users (50.4%) had 1 or more chronic illnesses, with rates increasing from 45.5% for patients with just 1 ED visit to 84.5% for the ultra-high users, meaning that the more they used the ED, the more likely they were to have a chronic illness. Overall burden of disease, as measured by the Charlson Comorbidity Index, also increased with ED use, from 1.15 for patients with a single visit to 3.20 for ultra-high users.

Rates of mental health and substance abuse were also high, at 23% and 35.1%, respectively, among ED users. However, substance abuse and mental health as reasons for the ED visit comprised just 5.2% and 4.9%, respectively.

The number of primary care visits the patient had made in both the index year and the year prior to the index ED visit increased with the number of ED visits, from 3.80 in the year prior and 3.89 in the index year for those with just one ED visit in 2007 to 6.72 and 7.45 primary care visits, respectively, for the ultra-high ED users.

The number of ED visits also predicted the number of nonobstetric inpatient admissions, from 0.24 for those with just 1 ED visit in the previous or index year, to 5.39 hospital admissions in the prior year and 7.34 in the index year for the ultra-high ED users. This suggests, Dr. Raven noted, that inpatient costs rather than the ED costs are responsible for the bulk of the overall encounter costs for Medicaid patients.

She acknowledged that these data are limited by factors that aren't captured in administrative data, such as housing situation, social support, and the quality of the primary care received.

Nonetheless, she said that the data clearly demonstrate that "ED use is not a major Medicaid cost driver, and frequent ED users often suffer from a substantial burden of illness that can require emergency care. The primary care delivery system must find ways to be more responsive to these patients, and the narrow focus on ED use seems misguided."

19. Duration of symptoms of respiratory tract infections in children: systematic review

Thompson M, et al. BMJ 2013;347:f7027

Objective To determine the expected duration of symptoms of common respiratory tract infections in children in primary and emergency care.

Design Systematic review of existing literature to determine durations of symptoms of earache, sore throat, cough (including acute cough, bronchiolitis, and croup), and common cold in children.

Data sources PubMed, DARE, and CINAHL (all to July 2012).

Eligibility criteria for selecting studies Randomised controlled trials or observational studies of children with acute respiratory tract infections in primary care or emergency settings in high income countries who received either a control treatment or a placebo or over-the-counter treatment. Study quality was assessed with the Cochrane risk of bias framework for randomised controlled trials, and the critical appraisal skills programme framework for observational studies.

Main outcome measures Individual study data and, when possible, pooled daily mean proportions and 95% confidence intervals for symptom duration. Symptom duration (in days) at which each symptom had resolved in 50% and 90% of children.

Results Of 22 182 identified references, 23 trials and 25 observational studies met inclusion criteria. Study populations varied in age and duration of symptoms before study onset. In 90% of children, earache was resolved by seven to eight days, sore throat between two and seven days, croup by two days, bronchiolitis by 21 days, acute cough by 25 days, common cold by 15 days, and non-specific respiratory tract infections symptoms by 16 days.

Conclusions The durations of earache and common colds are considerably longer than current guidance given to parents in the United Kingdom and the United States; for other symptoms such as sore throat, acute cough, bronchiolitis, and croup the current guidance is consistent with our findings. Updating current guidelines with new evidence will help support parents and clinicians in evidence based decision making for children with respiratory tract infections.

20. Millions of Opioid Prescriptions Go to 'Doctor Shoppers'

Nancy A. Melville. Medscape Medical News

Nearly 2% of all US opioid prescriptions, totaling an estimated 4.3 million prescriptions each year and 4% of all opioids by weight, are purchased by patients presumed to be "doctor shoppers," according to a new study.

In the first national estimate of opioid medications obtained in the United States by the doctor shoppers — patients who receive painkiller prescriptions from multiple doctors without informing the doctors of their other prescriptions — researchers found that they obtained, on average, 32 opioid prescriptions per year from 10 different prescribers.

The results are from evaluation of 146.1 million opioid prescriptions dispensed during 2008 by 76% of retail pharmacies. The findings were published online July 17 in the journal PLoS One. According to lead author Douglas McDonald, PhD, principle researcher with Abt Associates, of Cambridge, Massachusetts, the results showed 3 basic categories of prescriptions, with about 1 in 143 patients appearing to be doctor shoppers.

"For opioid prescribing, we found the vast majority of prescriptions were a matter of 1 doctor and 1 prescription," he told Medscape Medical News. "In the second category, there would be a patient receiving a few prescriptions from a few doctors, but these looked to me like patients in the chronic care population.

"And then in about 1 out of 143 were the outliers who looked different from the rest, with an average of 32 different prescriptions from 10 different prescribers."

Although the prescribers' exact intentions cannot be confirmed, Dr. McDonald said other factors that suggested doctor-shopping included the fact that the patients paid disproportionately in cash — a tactic used to avoid being detected by their insurers, and many were in their 20s and 30s, a group that has been shown in the substance abuse literature to have the highest rate of abuse.

"Exponentially" Increasing Problem 
The exponentially increasing problem of prescription opioid abuse is evidenced by the 4-fold increase in opioid overdose deaths, from 4000 in 1999 to 16,651 in 2010. The overdoses are now twice as common as heroin and cocaine overdose deaths combined, the authors note.

Opioid prescriptions meanwhile skyrocketed during the same general period: while the US population increased by just 16% between 1997 and 2011, the amount of oxycodone sold by retail pharmacies increased by 1259%.

The US Department of Justice took action to try to curtail the problem by making federal assistance available in 2002 for the computer-based prescription monitoring programs (PMPs) that collect data from pharmacies regarding dispensed prescriptions from certain drugs, including all schedule II drugs and several others. But those programs have not caught on with physicians, and currently only Kentucky and West Virginia legally require prescribers to access patients' prescription histories in the databases before prescribing certain drugs.

Among the key challenges in using PMPs is simply convincing physicians that they are worth the effort, Dr. McDonald said. "One of the problems of the PMP is it does require jumping through some hoops, such as password creation, and then looking up a prescription history, and that can take a significant amount of time and effort."

"My primary care provider, for instance, has 3000 patients, and if he were to use PMPs for even a 10th of those patients, that would be a lot of additional work in the scope of the traditional 15-minute appointment," he said.

"Furthermore, reimbursement rates don't offer much incentive for spending the time to evaluate someone for the risk of abuse and then take even more time to make referrals to treatment and find a treatment provider if they are a risk. So unfortunately, the easiest thing to do is to write a prescription and send them home."

Holes in the System 
Yet another problem is that PMPs only provide information for a particular state, which is a significant restriction, said Stuart Gitlow, MD, president of the American Society of Addiction Medicine. "I'm based in Rhode Island, for instance, but a patient could easily drive to Connecticut, Massachusetts, Vermont, or New Hampshire in no time at all and get multiple other prescriptions," said Dr. Gitlow, who practices in Woonsocket. "The more you look at it, the more you realize there are holes in the system.

"I do think prescription monitoring programs are way overdue, but we have to realize they have very significant limitations at the moment, and we need to solve that before they are as useful as promised," he added.

The study's authors and Dr. Gitlow agreed that the ideal situation would be for PMPs to be integrated into electronic medical records so that patients' prescription histories would be as easily accessible as their medical histories, but efforts toward that type of universal integration are only in the early stages. In the meantime, Dr. Gitlow suggested that physicians keep their eyes open for key clues that may suggest a patient is doctor-shopping.

"The typical concern is the individual who comes in asking for a drug specifically and says something like, 'I'm here for my Vicodin,' because the majority of patients do not want to take medication if they can avoid it," he said.

"Another thing is if you try to prescribe a particular drug and they say, 'No, not that one, I want this other one instead. I can only take Oxycontin and not Percocet,' for instance," he said. "If they have that much familiarity, that's a sign of a potential doctor shopper."

Physicians should also keep track of how much time has passed since a patient's last prescription. "Follow along over the course of time," he said. "If they do come in before they're really out of their medication and give excuses such as the medication is lost, it fell down the drain, or someone took it, those are big signs of problems."

The study was funded by the National Institute on Drug Abuse. Dr. McDonald and Dr. Gitlow have disclosed no relevant financial relationships.

21. Pulmonary Embolism Research

A. RV Dilatation on Bedside Echo Performed by Emergency Physicians Aids in the Diagnosis of PE

Dresden S, et al. Ann Emerg Med 2014;63:16-24.

Study objective: The objective of this study was to determine the diagnostic performance of right ventricular dilatation identified by emergency physicians on bedside echocardiography in patients with a suspected or confirmed pulmonary embolism. The secondary objective included an exploratory analysis of the predictive value of a subgroup of findings associated with advanced right ventricular dysfunction (right ventricular hypokinesis, paradoxical septal motion, McConnell's sign).

Methods: This was a prospective observational study using a convenience sample of patients with suspected (moderate to high pretest probability) or confirmed pulmonary embolism. Participants had bedside echocardiography evaluating for right ventricular dilatation (defined as right ventricular to left ventricular ratio greater than 1:1) and right ventricular dysfunction (right ventricular hypokinesis, paradoxical septal motion, or McConnell's sign). The patient's medical records were reviewed for the final reading on all imaging, disposition, hospital length of stay, 30-day inhospital mortality, and discharge diagnosis.

Results: Thirty of 146 patients had a pulmonary embolism. Right ventricular dilatation on echocardiography had a sensitivity of 50% (95% confidence interval [CI] 32% to 68%), a specificity of 98% (95% CI 95% to 100%), a positive predictive value of 88% (95% CI 66% to 100%), and a negative predictive value of 88% (95% CI 83% to 94%). Positive and negative likelihood ratios were determined to be 29 (95% CI 6.1% to 64%) and 0.51 (95% CI 0.4% to 0.7%), respectively. Ten of 11 patients with right ventricular hypokinesis had a pulmonary embolism. All 6 patients with McConnell's sign and all 8 patients with paradoxical septal motion had a diagnosis of pulmonary embolism. There was a 96% observed agreement between coinvestigators and principal investigator interpretation of images obtained and recorded.

Conclusion: Right ventricular dilatation and right ventricular dysfunction identified on emergency physician performed echocardiography were found to be highly specific for pulmonary embolism but had poor sensitivity. Bedside echocardiography is a useful tool that can be incorporated into the algorithm of patients with a moderate to high pretest probability of pulmonary embolism.

B. Clinical features of patients inappropriately undiagnosed of PE

Torres-Macho J, et al.  Amer J Emerg Med. 2013;31:1646-1650

Purposes: The objective of this study was to identify clinical factors associated with delayed diagnosis of acute pulmonary embolism (PE) in the emergency department (ED).

Basic procedures: A retrospective observational study was performed at three University affiliated Hospitals; 436 consecutive patients who presented to the ED with an acute PE confirmed by chest computed tomography from 2008 to 2011 were included. Patients were divided into 3 groups: group 1, PE was diagnosed while the patient was still in the ED; group 2, PE was diagnosed during hospitalization; group 3, patients who were sent home with a wrong alternative diagnosis and returned to the ED and were diagnosed of PE.

Main findings: One hundred forty-six patients (33.5%) had a delayed diagnosis of PE—21.5% belong to group 2 and 11.9% to Group 3. Chronic coexisting medical conditions like asthma or chronic obstructive pulmonary disease were independent predictors of a delayed diagnosis in patients who were admitted to hospital whereas non-specific and less severe symptoms like the presence of pleuro-mechanic thoracic pain, fever, hemoptysis, or the presence of a pulmonary infiltrate in chest x-ray were independent predictors of a delayed diagnosis in patients who were sent home.

Principal conclusions: Delay in diagnosis of acute PE is frequent despite current diagnostic strategies. Patients are sent home or admitted to hospital with a wrong diagnosis depending on clinical presentation or coexisting medical conditions.

C. Study Supports New Age-Adjusted D-Dimer Cutoffs for PE Testing

By Rob Goodier. NEW YORK (Reuters Health) Dec 17 - A new age-adjusted D-dimer cutoff level for pulmonary embolism (PE) testing passed muster with a failure rate of 0.3% in a study of nearly 3,400 patients.

For patients older than 50 years of age, the threshold is set at 10 times the patient's age in mcg/L.

"Our data suggest that this age-adjusted cutoff has significant potential in clinical practice to rule out suspected PE with a similar safety than the usual cutoff set at 500 mcg/L," Dr. Marc Righini in the Division of Angiology and Hemostasis at Geneva University Hospital in Switzerland, who led the study, said in a statement.

"When combined with clinical probability, the age-adjusted cutoff could increase the proportion of elderly patients in whom PE can be excluded without the use of more invasive imaging tests," Dr. Righini said.

Dr. Righini and his team presented their results December 10 at the annual meeting of the American Society of Hematology in New Orleans, Louisiana.

Their abstract for the meeting is available online here:

22. Pharmacology – Evaluating OTC Analgesia Risks

Evan Schwarz, MD, Emerg Physicians Monthly, November 28, 2013

It’s been another busy shift in the ED. You finish discharging one patient as you are pulling up the x-rays of a 24 year old who rolled his ankle while playing basketball. You don’t see a fracture and so you go into the room to tell him the good news that it is only a sprain. As you finish demonstrating some exercises that he can do to rehabilitate his ankle, he says, “Hey doc, what you gonna give me for this?” You tell him that you don’t think he needs narcotics, and given the epidemic of prescription opioid abuse and addiction, you think acetaminophen along with rest and ice should do the trick. You turn to walk out of the room when he responds, “Really, I heard on the radio that that stuff will kill you!” Somewhat shocked, you have a 10 minute conversation and finally agree to give him high dose ibuprofen and discharge him. Still shocked by that encounter, you fire up Dr. Google to try to learn more about this before your next shift.

The Dangers of Acetaminophen
A recent hour-long report on NPR’s This American Life discussed the dangers of acetaminophen. This was also the subject of a recent article on ProPublica. While the goal of making medications as safe as possible is commendable, the underlying message of how dangerous this medication can be may be overstated. They report that approximately 150 patients die each year after an accidental overdose of acetaminophen. While this is 150 patients too many, it also needs to be viewed in the context of how many people use acetaminophen each year, which is reportedly about 50 million people per year. This would mean less than 0.1% of patients exposed to acetaminophen each year die from an accidental overdose.

The report discussed a cohort of 47 patients that presented over 4 years to a single hospital following an overdose of acetaminophen. Of the 47, almost half were reported as unintentional overdoses. Of these 23 patients, three died and two required hepatic transplantation. The unintentional group tended to be sicker and do worse than the intentional group. This data was once again presented to illuminate the dangers of acetaminophen, and how easy it was to overdose as it had such a “narrow therapeutic margin.” However, other conclusions can also be drawn from this data. The unintentional group likely did worse, and was sicker, because of a delay in presentation compared to the intentional group. Also a higher percentage of patients were transferred from outside hospitals in the unintentional group, likely due to the fact that they had already developed acute liver injury and needed to go to a tertiary care center.

How patients were classified as unintentional overdoses may also be flawed. The support for them being unintentional was based on the fact that only 10/23 had a psychiatric evaluation in the hospital, while all the patients classified as an intentional overdose had a psychiatric evaluation. While the difference in psychiatric consultation rates between the two groups may be due to fewer suicide attempts in the unintentional group, there are also other explanations for this. As such, using psychiatric evaluation as a marker for intentional exposures may be flawed.

Much has also made regarding the narrow therapeutic margin of acetaminophen, especially compared to other over-the-counter NSAIDS. While the mechanism of action of acetaminophen is not clear, it appears to indirectly inhibit prostaglandin synthesis, mainly COX-2, in the CNS. Further investigation into their data shows that on average these patients were taking 8.1 grams of acetaminophen/day (range 1.1-18 grams/day). This is double the recommended dose,  not simply taking one or two extra tablets a day by accident. While an ingestion of 10 grams a day (approximately 150 mg/kg for a 70 kg individual) is mentioned as the toxic threshold, this is only for a single ingestion. It is well known that the toxic threshold decreases if you continue taking supratherapeutic doses multiple days in a row. More importantly, we know that acetaminophen taken at the maximum recommended dose of 4 grams a day is very safe. Patients were safely given 4 grams of acetaminophen a day for 4-6 weeks in multiple studies (Schnitzer 2005)(Bradley 1991). We even know the recommended dosing is safe in high-risk patients, such as with chronic alcoholics who recently stopped drinking. In addition to their baseline hepatic dysfunction this group was theoretically at an increased risk of an adverse event as they had upregulation of the enzymes responsible for producing the toxic metabolites of acetaminophen. But this group did well while taking 4 grams of acetaminophen a day for 3 consecutive days (Kuffner 2007).

One problem is that the term “narrow therapeutic margin” as used in these news reports  is incredibly subjective. Acetaminophen does have a much narrower margin compared to the amount of ibuprofen required in a single overdose to kill someone. However, an argument could also be made that acetaminophen has a much wider margin compared to many other medications such as verapamil, lithium, or colchicine, just to name a few.

In addition to the concern raised by PBS, many patients with chronic liver disease are also warned by their doctors to avoid acetaminophen. While I agree that long term use is probably not good for them, short term use for pain control in the ED and the next couple of days with re-evaluation by their primary care doctor or hepatologist seems reasonable for the majority of these patients. In this population other NSAIDS also have their drawbacks due to inhibiting platelet aggregation in a population with an elevated baseline risk of bleeding.

The safety of NSAIDS such as ibuprofen has also been questioned by the media…

23. Morphine Decreases Clopidogrel Concentrations and Effects: A Randomized, Double Blind, Placebo-Controlled Trial

Hobl E, et al. J Am Coll Cardiol. 2013 [Epub ahead of print]

Objectives  This study examined possible drug-drug interactions between clopidogrel and morphine.

Background  As morphine, the recommended treatment for pain of myocardial infarction is associated with poor clinical outcome, we hypothesized that morphine lowers the plasma levels of clopidogrel active metabolite as well as its effects on platelets.

Methods  Twenty-four healthy subjects received a loading dose of 600mg clopidogrel together with placebo or 5mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry and clopidogrel effects were measured by platelet function tests.

Results  Morphine injection delayed clopidogrel resorption (p=0.025), and reduced the area under the curve levels of its active metabolite by 52% (p=0.001). Morphine delayed the maximal inhibition of platelet aggregation on average by 2h (n=24; p greater than 0.001). Residual platelet aggregation was higher 1-4h after morphine injection (n=24; p greater than 0.005). Furthermore, morphine delayed the inhibition of platelet plug formation under high shear rates (P2Y-Innovance; n=21; p greater than 0.004), and abolished the 3-fold prolongation in collagen adenosine diphosphate induced closure times seen in extensive and rapid metabolizers (n=16; p=0.001).

Conclusions  Morphine delays clopidogrel resorption, decreases plasma levels of clopidogrel active metabolite, retards and diminishes its effects, which can lead to treatment failure in susceptible individuals.

24. Tid Bits

A. Early antibiotic use linked to higher odds of asthma, allergies

Children who were treated with antibiotics during the first two years of life were up to 1.75 times more likely to develop asthma by age 7.5 years than those unexposed to antibiotics, according to a study in the journal Pediatric Allergy and Immunology. The more the children used antibiotics early in life, the greater their risk of getting asthma. Researchers noted that exposure to antibiotics during infancy was also associated with increased risks of eczema and hay fever.

B. Connecting Brain and Machine

Bionic legs that use sensors and a control system to allow amputees to seamlessly traverse almost any terrain; robotic arms with a sophisticated brain-computer interface (BMI) allow paralyzed patients to closely match the speed and coordination of a typical human limb; even a computerized bladder that could eventually alert patients with spinal cord injury when to go to the bathroom.

These are just some examples of BMIs that harness electrical activity produced by neurons in the brain to control the movement of a variety of robotic devices. The hope is that in the not-too-distant future, patients with a variety of neurologic disorders may recover their mobility and leave their wheelchair and other clumsy assistive devices behind…

The remainder of the essay:

C. New guidelines revise BP targets for prescribing medication

New guidelines from an expert panel continue to call for blood pressure readings of 140/90 or higher before prescribing medication for patients ages 30 to 59, but recommend hypertension drugs for those age 60 and over only if readings hit at least 150/90. "I think we've simplified the drug regimen for family doctors," said lead author and family physician Paul James, M.D. The panel, writing in JAMA, did not make recommendations for treating blood pressure between 120/80 and 140/90, a point at which earlier guidelines said medication could be considered.

D. Data show outpatient physicians have more emotional exhaustion

A review of 54 studies on physician burnout found outpatient doctors reported being more emotionally exhausted than their hospital-based colleagues, according to researchers at the Mayo Clinic Hospital in Phoenix. The data, published in the Journal of Hospital Medicine, did not show significant differences in depersonalization or personal accomplishment.

E. Narrow- and broad-spectrum antibiotics work equally well in pneumonia

U.S. researchers looked at nearly 500 patients with pneumonia aged 2 months to 18 years and found no substantial differences in readmission rates, fever duration and length of oxygen time between those treated with narrow-spectrum antibiotics and those given broad-spectrum drugs. However, the study published in the journal Pediatrics showed that the length of stay in the narrow-spectrum group was 10 hours shorter than the broad-spectrum patients.

F. Gallup poll shows 30% put off medical care due to cost

A Gallup survey found 30% of adults said they or a family member had decided not to get medical care in the past year due to cost. Poll data showed almost 60% of uninsured respondents said they had delayed getting medical care, while fewer than 25% of Medicare and Medicaid patients put off treatment.

G. Physicians’ Preferences for Hospice if They Were Terminally Ill and the Timing of Hospice Discussions With Their Patients

Physicians often delay hospice discussions with their terminally ill patients despite guidelines recommending such discussions for patients expected to die within 1 year,1,2 but reasons for this are not well understood. Evidence suggests that physicians “practice what they preach” when counseling about health behaviors,3 although their treatment recommendations may not necessarily reflect their own preferences, with one study suggesting they recommend more conservative treatments than they might choose for themselves.4 As physicians may prefer less aggressive end-of-life care than their patients generally receive,5 physicians’ personal preferences for hospice may influence their approach to hospice discussions with their terminally ill patients.

H. What Is Wrong With Discharges Against Medical Advice (and How to Fix Them)

It is estimated that as many as 2% of all US hospital discharges (approximately 500 000 per year) are designated as against medical advice1; that is, a patient chooses to leave the hospital before the treating physician recommends discharge. The risks to these patients are significant. Compared with patients discharged conventionally, readmission rates for patients discharged against medical advice are 20% to 40% higher, and their adjusted relative risk of 30-day mortality may be 10% higher.2 Furthermore, physicians and other health care staff report feeling distressed and powerless when patients choose suboptimal care, and disagreement over a discharge against medical advice can cause patient-physician and intrateam conflict.3