Tuesday, August 30, 2016

Lit Bits: Aug 30, 2016

From the recent medical literature...

1. Using RNA expression profiling to differentiate children with bacterial disease from those with viral disease

A. Genetics and the Evaluation of the Febrile Child

Bauchner H. JAMA. 2016;316(8):824-825.

Clinicians who care for children have encountered the same questions for decades: does the child have an infection, is it likely bacterial or viral, and is an antibiotic indicated? These questions were further complicated by the “discovery” of bacteremia. In 1973-1974, Teele et al1 obtained blood cultures from 600 consecutive febrile children younger than 2 years with temperatures of 38.3°C or higher and found that 19 (3.2%) had pathogens in their blood. Streptococcus pneumoniae was the most common pathogen (n = 15), followed by Haemophilus influenzae type b (n = 2). Further analysis suggested that children with a temperature higher than 38.9°C and a white blood cell count greater than 15 000/μL had about an 8% to 10% risk of “bacteremia.” For the following 3 decades, the focus was on determining how to identify these children; how these children could be differentiated into groups at high and low risk for bacteremia by various clinical scores or laboratory tests, such as C-reactive protein, erythrocyte sedimentation rate, or neutrophil-to-band ratio; and if expectant antibiotics are necessary.2,3

Following the introduction of the conjugate H Influenzae vaccine in the late 1980s, the number of children with bacteremia (and meningitis) declined substantially, with a further decline following the introduction of the conjugate pneumococcal vaccine in 1990s.4- 7 Prior to the introduction of these 2 vaccines, approximately 20 000 children each year were diagnosed with meningitis and other serious bacterial infections, such as epiglottitis, caused by these organisms.6,7 In 2015, fewer than 500 children were diagnosed with invasive H influenzae type b or invasive pneumococcal disease.4,5

At the same time invasive disease was declining among older children, the focus shifted to identifying infants younger than 90 days with serious bacterial infection (SBI), such as meningitis, septicemia, and urinary tract infections.8- 10 Many febrile infants younger than 30 days presenting to an emergency department were admitted to the hospital, often after they had blood cultures, urine cultures, and a lumbar puncture performed. The vast majority received antibiotics. In this age group, approximately 5% to 8% of infants presenting with fever to an emergency department have serious bacterial infection.8- 10 Management is different in infants older than 30 days (in some settings older than 2 weeks), for whom various approaches have been adopted that help clinicians categorize children into high and low risk for SBI and potentially discharge them home from an emergency department, with or without antibiotics. However, these scenarios are often not the same in office practice, with apparently few “missed” infants with SBI.11 Although the data are uncertain, it is likely that infants presenting to an emergency department have a higher risk of SBI than those in practice, and follow-up may be more difficult, necessitating a different clinical approach.

Two articles in this issue of JAMA contribute to the 5-decades-long discussion of the evaluation of febrile infants and children and represent an important advance—the potential of genetics to help in the evaluation of febrile children.12,13 Specifically, can RNA expression profiling be successful when clinical scores and other laboratory tests (aside from blood culture results) have largely failed to differentiate children with bacterial disease from those with viral disease? The questions are different depending on the age of the child. Among very young infants, the goal of a laboratory test is to rule out SBI, with a very high degree of certainty (high sensitivity). Among older children, in whom the risk of SBI is much lower, the goal is to differentiate bacterial from viral infection, so the clinician does not have to prescribe antibiotics, an increasingly important consideration because of concerns about antibiotic resistance.

In one study in this issue of JAMA, Mahajan and colleagues12 assessed the association between RNA biosignatures and bacterial infection in 279 randomly selected febrile infants 60 days of age and younger (median age, 37 days; 56% male), of whom 89 had bacterial infections—including 32 with bacteremia and 58 with urinary tract infection—190 without bacterial infections, and 19 afebrile healthy infants. Sixty-six genes were identified that best discriminated infants with and without bacterial infection. In the validation test set, the sensitivity was 87% (95% CI, 73%-95%) and the specificity was 89% (95% CI, 81%-93%). In a subset of infants with bacteremia, the sensitivity in the validation test set was 94% (95% CI, 70%-100%) and the specificity was 95% (95% CI, 88%-98%). The authors acknowledge a number of limitations, including a convenience sample of patients, viral testing was not consistently performed on all patients, and the assays were performed on frozen batched samples in a central laboratory.

In another study in this issue, Herberg and colleagues13 determined if RNA expression measured by microarray could be used to differentiate bacterial from viral infection in 370 children (median age, approximately 18 months), of whom 86 had a definitive bacterial infection, 120 a viral infection, and 175 an indeterminate infection. The authors identified a 2-transcript RNA biosignature that could differentiate bacterial from viral infection. In the validation set, the sensitivity was 100% (95% CI, 100%-100%) and the specificity was 96.4% (95% CI, 89.3%-100%). This study also has a number of limitations, such as use of a case-control design with a high acuity of illness for many of the cases, so the actual number of children with bacterial and viral infection does not reflect the frequency of infections in clinical practice. In addition, the spectrum of the type of infections is likely different in practice. That being said, a 2-transcript biosignature, if proven to be robust in future studies, might be amenable to the development of a near real-time clinical assay.

The results of these 2 preliminary studies represent promissory notes. Clearly, RNA sequencing and other techniques for RNA quantitation are in the early days of development and evaluation for clinical applications. There have been other promissory notes—for example, the utility of C-reactive protein to differentiate children into high and low risk and the availability of rapid diagnostic testing to confirm a viral infection. The substantial decline in the prevalence of SBI, following the introduction of conjugate vaccines, has made clinical decision making more difficult—the needle has become much smaller, and the haystack much larger, particularly in young infants. However, if the promises of findings reported in the studies by Mahajan and colleagues and Herberg and colleagues are fulfilled by replication and refinement in other rigorous investigations, it may be possible that such advances will further reduce morbidity, mortality, and costs associated with caring for febrile children. The day when a parent of a febrile child may do a laboratory test at home, call a physician, and mutually decide if that child should be seen for evaluation may soon be here.

B. Association of RNA Biosignatures with Bacterial Infections in Febrile Infants Aged 60 Days or Younger

Mahajan P, et al. JAMA. 2016;316(8):846-857.

Key Points
Question Can the host response measured by RNA biosignatures distinguish young febrile infants with and without bacterial infections?

Findings In this prospective observational study of 279 febrile infants 60 days or younger, 66 classifier genes distinguished infants with and without bacterial infections with 87% sensitivity and 89% specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections with 94% sensitivity and 95% specificity.

Meaning In this preliminary study, host RNA biosignatures accurately distinguished febrile infants 60 days or younger with and without bacterial infections

Importance  Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns (“RNA biosignatures”) in response to infections may provide an alternative diagnostic approach.

Objective  To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections.

Design, Setting, and Participants  Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature greater than 38° C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type.

Exposure  RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections.

Main Outcomes and Measures  Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores.

Results  Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections—including 32 with bacteremia and 15 with urinary tract infections—and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and 95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43).

Conclusions and Relevance  In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.

C. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children

Herberg JA, et al. JAMA. 2016;316(8):835-845.

Key Points
Question Can febrile children with bacterial infection be distinguished from those with viral infection and other common causes of fever using whole-blood gene expression profiling?

Findings In this cross-sectional study that included 370 febrile children, those with bacterial infection were distinguished from those with viral infection with a sensitivity in the validation group of 100% (95% CI, 100%-100%) and specificity of 96.4% (95% CI, 89.3%-100%), using a 2-transcript signature.

Meaning This study provides preliminary data on the performance of a 2-transcript host RNA signature for discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings.

Importance  Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others.

Objective  To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children.

Design, Setting, and Participants  Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets.

Exposures  A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis.

Main Outcomes and Measures  Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group.

Results  The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 100%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment.

Conclusions and Relevance  This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings.

2. Age-adjusted DD Wins…Again

Wells Rule and d-Dimer Testing to Rule Out PE: A Systematic Review and Individual-Patient Data Meta-analysis

van Es N, et al. Ann Intern Med.  2016;165(4):253-261.

Background: The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear.

Purpose: To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older.

Data Sources: MEDLINE and EMBASE from 1 January 1988 to 13 February 2016.

Study Selection: 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing.

Data Extraction: Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool.

Data Synthesis: The proportion of patients in whom imaging could be withheld based on a “PE-unlikely” Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged greater than 50 years) d-dimer thresholds; their 3-month incidence of symptomatic venous thromboembolism (failure rate) was also estimated. Overall, efficiency increased from 28% to 33% when the age-adjusted (instead of the fixed) d-dimer threshold was applied. This increase was more prominent in elderly patients (12%) but less so in inpatients (2.6%). The failure rate of age-adjusted d-dimer testing was less than 3% in all examined subgroups.

Limitation: Post hoc analysis, between-study differences in patient characteristics, use of various d-dimer assays, and limited statistical power to assess failure rate.

Conclusion: Age-adjusted d-dimer testing is associated with a 5% absolute increase in the proportion of patients with suspected PE in whom imaging can be safely withheld compared with fixed d-dimer testing. This strategy seems safe across different high-risk subgroups, but its efficiency varies.

Bottom line
In most patients older than 50 years with suspected PE, an age-adjusted cutoff for D-dimer should be used with the Wells rule to exclude the diagnosis.

An age-adjusted D-dimer cutoff seems to be safe across a wide range of subgroups (including patients with chronic obstructive pulmonary disease, cancer, venous thrombosis, and age older than 75 years).

In hospitalized patients, the age-adjusted D-dimer cutoff was associated with a modest 2.6% increase in the number of patients who could be ruled out for PE. Therefore, the efficiency of this approach for inpatients may be somewhat limited.

3. Neither Acetaminophen nor Ibuprofen Aggravate Pediatric Asthma

There has been concern that acetaminophen may exacerbate asthma. These investigators found no difference in asthma control among young children treated for minor illnesses with acetaminophen as compared with ibuprofen.

Sheehan WJ, et al. Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. N Engl J Med. 2016 Aug 18;375(7):619-630.

Background Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.

Methods In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial.

Results Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events.

Conclusions Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen.

Editorial: Acetaminophen and Asthma — A Small Sigh of Relief?

Acetaminophen is the drug of choice for fever in young children. Pediatricians, parents, and caregivers consider it to be safe for most children when it is administered in accordance with the manufacturer’s directions for use. In 2000, however, concern was raised about the safety of acetaminophen as a result of the findings of a case–control study by Shaheen et al.1 that suggested that frequent use of acetaminophen (also known as paracetamol in the United Kingdom) among adults was associated with asthma, and among those who already had asthma, with more severe disease. The mechanism for this association was thought to be the depletion of glutathione in the lung, leading to greater oxidative stress. This concern led to more than a decade of observational research on acetaminophen use and asthma in adults,2 as well as in children and in pregnant women. The three main questions that the studies attempted to answer were whether frequent acetaminophen use (either prenatal or postnatal) leads to asthma in children who would otherwise be asthma-free, whether frequent acetaminophen use in children and adults who already have asthma worsens symptoms, and whether ibuprofen is safer than acetaminophen with respect to these asthma-related issues.

The limitation of observational studies in assessing the risk associated with these common over-the-counter medications is confounding by indication3 (i.e., people who use a drug more frequently differ in key characteristics from those who use the drug less frequently or who do not use the drug at all). In the case of studies evaluating an association between acetaminophen use and asthma in children, viral respiratory illnesses are the most common causes of wheezing among children with asthma, but because these illnesses also cause fever and aches (two potential indications for acetaminophen), it is difficult to determine a causal association. Therefore, there have been calls for well-performed clinical trials to settle the issue of causation.2,4

4. ACEP Clinical Policy: Critical Issues in the Evaluation of Adults with Suspected TIA in the ED

Lo BM, et al. Ann Emerg Med. 2016;68(3):354–370.e29.

This clinical policy from the American College of Emergency Physicians addresses key issues for adults presenting to the emergency department with suspected transient ischemic attack. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical questions:
(1) In adult patients with suspected transient ischemic attack, are there clinical decision rules that can identify patients at very low short-term risk for stroke who can be safely discharged from the emergency department?

(2) In adult patients with suspected transient ischemic attack, what imaging can be safely delayed from the initial emergency department workup?

(3) In adult patients with suspected transient ischemic attack, is carotid ultrasonography as accurate as neck computed tomography angiography or magnetic resonance angiography in identifying severe carotid stenosis?

(4) In adult patients with suspected transient ischemic attack, can a rapid emergency department-based diagnostic protocol safely identify patients at short-term risk for stroke? Evidence was graded and recommendations were made based on the strength of the available data.

5. When diuretics may not be the place to start in the ED treatment of HF

Collins SP, et al. Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society for Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group. Acad Emerg Med. 2016;23(8):922-931.


Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease that is based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF.

Suggested Management of Hypertensive Acute HF
1. Administer oxygen as needed to keep saturation 95% or greater, give sublingual nitroglycerin. Sublingual nitroglycerin may be repeated up to one per minute

2. If severe dyspnea, consider NIV or intubation.  

3. If blood pressure is greater than 150/100 mm Hg, add IV nitroglycerin or nitroprusside; if blood pressure falls below 100 mm Hg, stop nitrates or nitroprusside, monitor for persistent hypotension or symptoms. If blood pressure is less than 150/100 mm Hg after sublingual administration and if clinically improved, consider transdermal nitroglycerin. See text for discussion of these agents.

4. Start IV loop diuretic (furosemide or bumetanide or torsemide) in the setting of volume overload.  Initiate nitrates before diuretics.

5. Assess for severity of illness/high risk: altered mental status persistent, hypoxia despite NIV, hypotension, troponin elevation, ischemic ECG changes, blood urea nitrogen over 43, creatinine over 2.75, tachycardia, tachypnea, or inadequate urine output.  

6. Admit to ICU if high severity of illness or risk of decompensation.  

7. Choose discharge or ED observation unit admission if good response to therapy and no need for ongoing IV vasodilators, no high-risk features, and good social support. Admit the rest, ICU if any ongoing cardiorespiratory compromise or acute ischemia. Scoring systems may not reliably identify all patients at risk…

Conclusion and Future Directions
The hallmark of patients presenting to the ED with hypertensive acute heart failure is an altered relationship between ventricular and vascular function, leading to reduced cardiovascular reserve and an inability to adequately accommodate increases in venous return. Arterioles adapt to chronic increases in arterial pressure associated with hypertension, resulting in increased afterload triggering early aortic valve closure. An immediate consequence is increased diastolic volume and pressure. Subsequent increases in pulmonary venous pressures may result in pulmonary congestion. Many of these patients are older with concomitant renal disease. Preliminary data raise the possibility that future treatment might be better focused on preload and afterload reduction with vasodilators rather than volume removal with diuretics…

Article link (full-text requires subscription): http://onlinelibrary.wiley.com/doi/10.1111/acem.13025/abstract

6. External validation of the ED assessment of CP score accelerated diagnostic pathway (EDACS-ADP).

Flaws D, et al. Emerg Med J. 2016 Sep;33(9):618-25.

OBJECTIVE: The emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP) facilitates low-risk ED chest pain patients early to outpatient investigation. We aimed to validate this rule in a North American population.

METHODS: We performed a retrospective validation of the EDACS-ADP using 763 chest pain patients who presented to St Paul's Hospital, Vancouver, Canada, between June 2000 and January 2003. Patients were classified as low risk if they had an EDACS below 16, no new ischaemia on ECG and non-elevated serial 0-hour and 2-hour cardiac troponin concentrations. The primary outcome was the number of patients who had a predetermined major adverse cardiac event (MACE) at 30 days after presentation.

RESULTS: Of the 763 patients, 317 (41.6%) were classified as low risk by the EDACS-ADP. The sensitivity, specificity, negative predictive value and positive predictive value of the EDACS-ADP for 30-day MACE were 100% (95% CI 94.2% to 100%), 46.4% (95% CI 42.6% to 50.2%), 100% (95% CI 98.5% to 100.0%) and 17.5% (95% CI 14.1% to 21.3%), respectively.

CONCLUSIONS: This study validated the EDACS-ADP in a novel context and supports its safe use in a North American population. It confirms that EDACS-ADP can facilitate progression to early outpatient investigation in up to 40% of ED chest pain patients within 2 hours.

7. FABS: An Intuitive Tool for Screening of Stroke Mimics in the ED

Goyal N, et al. Stroke. 2016 Sep;47(9):2216-20.

BACKGROUND AND PURPOSE: A large number of patients with symptoms of acute cerebral ischemia are stroke mimics (SMs). In this study, we sought to develop a scoring system (FABS) for screening and stratifying SM from acute cerebral ischemia and to identify patients who may require magnetic resonance imaging to confirm or refute a diagnosis of stroke in the emergency setting.

METHODS: We designed a scoring system: FABS (6 variables with 1 point for each variable present): absence of Facial droop, negative history of Atrial fibrillation, Age less than 50 years, systolic Blood pressure less than 150 mm Hg at presentation, history of Seizures, and isolated Sensory symptoms without weakness at presentation. We evaluated consecutive patients with symptoms of acute cerebral ischemia and a negative head computed tomography for any acute finding within 4.5 hours after symptom onset in 2 tertiary care stroke centers for validation of FABS.

RESULTS: A total of 784 patients (41% SMs) were evaluated. Receiver operating characteristic curve (C statistic, 0.95; 95% confidence interval [CI], 0.93-0.98) indicated that FABS≥3 could identify patients with SM with 90% sensitivity (95% CI, 86%-93%) and 91% specificity (95% CI, 88%-93%). The negative predictive value and positive predictive value were 93% (95% CI, 90%-95%) and 87% (95% CI, 83%-91%), respectively.

CONCLUSIONS: FABS seems to be reliable in stratifying SM from acute cerebral ischemia cases among patients in whom the head computed tomography was negative for any acute findings. It can help clinicians consider advanced imaging for further diagnosis.

8. Short-term Prognosis and Current Management of Syncopal Patients at Intermediate Risk: Results from the IRiS (Intermediate-Risk Syncope) Study.

Numeroso F, et al. Acad Emerg Med. 2016 Aug;23(8):941-8.

OBJECTIVES: Despite guidelines, admission rates and expenditures for syncope remain high. This may be caused by an imprecise definition of cardiovascular disease considered at risk and an overestimation of the role of comorbidities and advanced age. In a cohort of patients with undetermined syncope, we prospectively compared the short-term prognosis of patients at intermediate risk (i.e., with stable heart diseases or comorbidities, of any age) versus those at high risk for cardiogenic syncope and identified factors associated with serious events. Secondarily, we analyzed the current management of intermediate-risk patients.

METHODS: In a cohort of patients with undetermined syncope, we analyzed personal data, the presence of stable heart diseases or comorbidities, destination, length of hospitalization, incidence of serious events at 30 days, and costs.
RESULTS: In a 6-month period, 347 patients (185 male and 162 female, age 72.8 years) with undetermined syncope were enrolled, 250 at intermediate risk and 97 at high risk. Intermediate-risk patients were younger, with less frequent comorbidities and with a drastically lower incidence of serious events (0.8% vs. 27.8%, p less than 0.001). Risk factors for cardiogenic syncope were the unique variable associated with serious events. Intermediate-risk patients were mostly admitted (62.8%) in an ordinary ward or into an emergency department observation unit; in the case of ordinary admission we observed a mean prolonged hospitalization (8.8 days), elevated costs ($270,183), and a high rate of unexplained syncope (51%).

CONCLUSIONS: According to the results of this study, the authors believe that intermediate-risk patients could be safely discharged, with potentially significant costs saving. In prognostic stratification, priority is to seek risk factors for cardiogenic syncope while advanced age, stable heart diseases, or comorbidities likely lead to inappropriate hospitalization.

A prospective interventional study is needed to validate our results. In the prognostic stratification of patients with syncope, factors such as stable cardiovascular diseases or comorbidities and advanced age, which often characterize syncopal patients at intermediate risk, should not lead per se to hospitalization because they are not related to serious events. On the contrary, emergency physicians should promptly identify patients at high risk for cardiogenic syncope to be hospitalized for thorough evaluation, due to the high incidence of serious short-term adverse events.

What constituted high risk?
Family history of SCD
Syncope during exertion or supine
Palpitations or chest pain
Strong systolic ejection murmur
Bifascicular block or other block with QRS greater than 120 msec
Inadequate sinus bradycardia or sinoatrial block
Preexcited QRS complex
Prolonged or short QT interval
Brugada pattern type1 or ECG changes suggestive for arrhythmogenic RV cardiomyopathy

9. What is the purpose of log roll examination in the unconscious adult trauma patient during trauma reception?

Singh Tveit M, et al. Emerg Med J. 2016 Sep;33(9):632-5.

BACKGROUND: During assessment after injury, the log roll examination, in particular palpation of the thoracolumbar spine, has low sensitivity for detecting spinal injury. The manoeuvre itself requires a pause during trauma resuscitation. The aim of this study was to assess the utility of the log roll examination in unconscious trauma patients for the diagnosis of soft tissue and thoracolumbar spine injuries.

METHODS: A retrospective cohort study was undertaken, reviewing the cases of unconscious (Glasgow Coma Scale (GCS) less than 9) and/or intubated major trauma (Injury Severity Scale (ISS) greater than 12, abbreviated injury scale 2008) patients from the Alfred Trauma Registry, over a 2-year period from January 2011 to December 2012. Log roll examination findings, as documented in the medical record, were compared with CT reports. Out of the 624 screened records, 222 (35.6%) were excluded as the log roll or CT/MRI had not been performed.

RESULTS: There were a total of 2028 major trauma presentations to the Alfred Hospital Emergency and Trauma Centre during the study period. Excluded cases comprised 147 patients who did not have a documented log roll, and 75 patients who did not have a CT or MRI. Of the 402 cases that met inclusion criteria, 35.3% had a thoracolumbar fracture, and the sensitivity of log roll examination was found to be 27.5%, with a specificity of 91%. The negative likelihood ratio for abnormalities on log roll was low (0.8).

CONCLUSIONS: Examination of the back in unconscious trauma patients could be limited to visual inspection only to allow identification of penetrating wounds and other soft tissue injuries (including of the posterior scalp) and removal of foreign bodies, in patients planned for CT scans. The low sensitivity and poor negative likelihood ratio suggest that a normal log roll examination does not accurately predict the absence of bony injury to the thoracolumbar spine.

10. Images in Clinical Practice

I'd Want a Natural Death

Takayasu’s Arteritis

Gastric Anisakiasis

Aortic Calcification and Superior-Mesenteric-Artery Stenosis

Enlarged Right Atrium

Urticaria Multiforme

Giant Thrombosed Intracranial Aneurysm

A Sneeze

Young Man With Dyspnea

Young Male With Painful Skin Necrosis

Man With Altered Mental Status and Rash

Man With Diminished Breath Sounds on the Right

Man With Right-Sided Abdominal Pain

Woman With Vision Loss in Left Eye

Newborn With Vomiting

Man With Bleeding Gums and Skin Rash

Discussion: Remember to Take Your Vitamins…

Elderly Woman With Chest Pain

Woman With Sudden-Onset Headache

11. Treatment with Prothrombin Complex Concentrate to Enable Emergency LP in Patients Receiving Vitamin K Antagonists.

Laible M, et al. Ann Emerg Med. 2016;68(3):340–344.

STUDY OBJECTIVE: Lumbar punctures are frequently necessary in neurologic emergencies, but effective oral anticoagulation with vitamin K antagonists represents a contraindication. We report the effectiveness of prothrombin complex concentrates to reverse vitamin K antagonist to enable emergency lumbar punctures, as well as evaluate lumbar puncture- and prothrombin complex concentrates-related complications.

METHODS: Consecutive patients treated with prothrombin complex concentrates between December 2004 and June 2014 to enable emergency lumbar puncture were included. International normalized ratio (INR) before and after prothrombin complex concentrates treatment and the time between start of reversal treatment and lumbar puncture were recorded. A target INR of less than or equal to 1.5 was defined as effective prothrombin complex concentrates treatment. Bleeding events, thromboembolic events, and allergic reactions after prothrombin complex concentrates treatment were identified and classified as "related," "probably," "possibly," "unlikely related," or "not related" to the lumbar puncture and prothrombin complex concentrates infusion.

RESULTS: Thirty-seven patients were included (64.9% men; median age 76.0 years; interquartile range [IQR] 71.0 to 84.0 years). The intervention with prothrombin complex concentrates was effective in 33 of 37 patients (89.2%; 95% confidence interval [CI], 78.4% to 97.3%). The median INR was 2.2 (IQR 1.8 to 2.9; 95% CI, 1.9 to 2.5) before and 1.3 (IQR 1.2 to 1.4; 95% CI, 1.2 to 1.3) after prothrombin complex concentrates treatment. The median time between start of prothrombin complex concentrates treatment and lumbar puncture was 135 minutes (IQR 76 to 266 minutes; 95% CI, 84 to 198 minutes). One clinically irrelevant intracranial subdural hematoma "related" to the lumbar puncture developed. No allergic reaction was observed, but 2 of 37 patients (5.4%; 95% CI, 0% to 13.5%) experienced a thromboembolic event (1 ischemic stroke, classified "unlikely related," and 1 myocardial infarction, "possibly related" to prothrombin complex concentrates treatment).

CONCLUSION: Reversing the effect of vitamin K antagonist with prothrombin complex concentrates to enable emergency lumbar puncture appears effective and safe, particularly in regard to bleeding events.

12. Lancet Articles on ACS Management

A. Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study

Wallentin L, et al. Lancet 2016 Aug 29 [Epub ahead of print]

Background: The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up.

Methods: The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat.

Findings: At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204–888; p=0·0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402–1175; pinteraction=0·0182), patients with elevated troponin T (778 days, 357–1165; pinteraction=0·0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507–1650; pinteraction=0·0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830–1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p less than 0·0001).

Interpretation: During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.

B. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial

Cayla G, et al. Lancet 2016 Aug 28 [Epub ahead of print]

Background: Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the therapeutic risk–benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome.

Methods: We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months' follow-up. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01538446.

Findings: Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio [HR], 1·003, 95% CI 0·78–1·29; p=0·98). Rates of bleeding events did not differ significantly between groups.

Interpretation: Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations.

13. Waiting Room Medicine

A. Fellowship Training Opportunities

Lund A. CJEM 2007;9(1):71

The Department of Emergency Medicine at Any Canadian Hospital (ACH) is actively seeking qualified applicants for a 6-month fellowship position in the emerging Emergency Medicine (EM) subspecialty of Waiting Room (WR) Medicine.

This unique opportunity is being offered through the busy waiting room of the Emergency Department (ED) at ANY CANADIAN HOSPITAL, a premiere teaching institution with the University of Said Province.

The Setting
The ED sees in excess of 65,000 patients per year (mostly in the waiting room!), and is the trauma receiving hospital for the region. Located in or near a great Canadian city, there are many recreational opportunities for interested applicants (which is important because, truth be told, the work is not so rewarding).

The Crowding Problem
Access to inpatient beds for acutely ill patients in Canada has been consistently decreasing over the last decade. Many EDs have been paralyzed by the admitted patients in their stretchers warehoused in their hallways. Emergency Physicians (EPs) have little formal training in providing medical care outside of the usual confines of an actual bed with a nurse available to provide care. Clearly, this training deficit leaves most EPs behind the times.  Much of the care provided in contemporary EDs is done in chairs, on ambulance gurneys, behind temporary curtains, or in broom closets, bathrooms, offices, and of course, in the waiting room. With the ever increasing demand for Waiting Room Medicine, we see a fabulous opportunity to foster the unique skill-set of WR medicine in EM learners and EPs seeking higher levels of training.

Rotations include
• Unmonitored Cardiology — Make decisions about which of the 6 patients with crushing chest pain should get the next available bed when it opens up in the morning.
• WR Surgery — You’d be surprised how many things you can sew, lance, drain and wrap in a simple WR chair.
• Communication Skills — Key objectives for the communication skills module include learning how to ask embarrassing questions in front of a crowd, learning to say “I’m sorry for the care you’re receiving” in a manner that doesn’t lead to your being assaulted by angry family members, and learning to say “these curtains are soundproof” with a straight face.
• EMS — Deal with ambulance diversion, critical care bypass; provide catering and nutritional requirements for waiting ambulance crews. Gain valuable skills in diverting ambulances with seriously ill patients from your ED to another equally overcrowded ED.
• Lab & Radiology — Learn to make judicious use of investigations based on a triage note and/or EMS report; no need to bother yourself with talking to or examining the patient until all the labs are back.
• Triage in the Real World — Practise reverse triage, where CTAS (triage acuity score) IVs and Vs are seen expeditiously, because they are “quick and easy,” and CTAS IIs and IIIs are left to languish for hours.
• WR Ethics — Triage the conflicting values of good patient care and maintaining the flow.
• WR Admin Interactions — Dealing with disappointment; how to carry on after seeking help from the administrators on call.
• WR Patients as Monitors — Learning to use other WR patients for the reassessment of critically ill patients (with a focus on teaching lay people about the recognition of seizures, initial management of cardiac arrest, and guidelines for involving the triage nurse in WR care)…

B. Initiating Diagnostic Studies on Patients With AP in the Waiting Room Decreases Time Spent in an ED Bed: A RCT

Begaz T. Ann Emerg Med. 2016 Aug 12 [Epub ahead of print]

Study objective
The effect of clinician screening of patients in the emergency department (ED) waiting room is unclear. This study aims to determine the effect of initiating laboratory and imaging studies from the ED waiting room on time in a bed, total ED time, and likelihood of patients leaving before completion of service.

This was a prospective, randomized, controlled trial evaluating 1,659 nonpregnant adults with a chief complaint of abdominal pain, conducted in a public hospital ED when all ED beds were occupied and patients were in the waiting room awaiting definitive evaluation. After a brief screening examination, stable patients were randomized to either rapid medical evaluation (RME)+waiting room diagnostic testing (WRDT) or RME-only groups. Patients randomized to the RME+WRDT group had laboratory and imaging studies ordered at the discretion of the screening provider while in the waiting room. The primary outcome was time in an ED bed. Secondary outcomes were total ED time and rate of leaving before completion of service. Linear and logistic regression models were used to compare outcomes between groups.

Between July 2014 and May 2015, 1,659 patients completed the study, 848 patients in the RME+WRDT group and 811 in the RME-only group. Baseline demographic characteristics were similar between groups. Patients in the RME+WRDT group had a significantly shorter mean time in an ED bed than the RME-only group, 245 minutes compared with 277 minutes (adjusted difference of 31 minutes; 95% confidence interval [CI] 16 to 46 minutes). The RME+WRDT group also had significantly shorter mean total ED time from arrival to disposition than the RME-only group, 460 minutes compared with 504 minutes (adjusted difference 42 minutes; 95% CI 22 to 63 minutes). Of the 1,659 patients enrolled, 181 left before completion of service: 78 of 848 patients (9%) in the RME+WRDT group compared with 103 of 811 (13%) in the RME-only group (difference 3.5%; 95% CI 0.5% to 6.5%). By the end of their ED visit, patients in the RME+WRDT group had significantly more types of diagnostic studies ordered than those in the RME-only group, 2.59 versus 2.03 total unique test categories by location ordered (difference 0.56; 95% CI 0.44 to 0.68).

Initiating diagnostic testing in the waiting room reduced time spent in an ED bed, total ED time, and rates of leaving before completion of service. For clinicians screening patients in the waiting room, initiating diagnostic evaluations may improve throughput in crowded EDs.

Comments from Ryan Radecki: http://www.emlitofnote.com/?p=3553

14. Reviews from Ann Emerg Med

A. Can Ocular Ultrasonography Be Used to Assess Intracranial Pressure?

Take-Home Message
Measurement of the optic nerve sheath diameter demonstrates good diagnostic test accuracy for differentiating between elevated and normal intracranial pressure when compared with computed tomography (CT). Specifically, the high sensitivity allows the clinician to rule out increased intracranial pressure in low-risk patients, whereas the high specificity can confirm elevated intracranial pressure in those at high risk.

B. Can Noncontrast Head CT Within 6 Hours of Symptom Onset Exclude Aneurysmal SAH?

Take-Home Message
A normal result for noncontrast head computed tomography (CT) obtained within 6 hours of symptom onset appears to substantially decrease the likelihood of subarachnoid hemorrhage.

C. Is a Single High-Sensitivity Troponin T Assay Accurate for the Detection of Acute Myocardial Infarction?

Take-Home Message
In high-risk chest pain patients, a single, normal, high-sensitivity troponin T level identifies those who are very unlikely to have acute myocardial infarction, yet the optimal diagnostic threshold and timing remain unclear.

D. Periprosthetic Joint Infection after Hip and Knee Arthroplasty: A Review for Emergency Care Providers

Intro’s opener: Periprosthetic joint infection is among the most common modes of failure of a total hip or knee arthroplasty and can be a common concern when patients present to the emergency department for care. The initial evaluation for periprosthetic joint infection includes a history and physical examination, followed by radiographs (to rule out other causes of pain or failure) and then serum erythrocyte sedimentation rate and C-reactive protein testing. If the erythrocyte sedimentation rate and C-reactive protein level are elevated or if the clinical suspicion for infection is high, the joint should be aspirated and the fluid sent for culture, as well as for a synovial WBC count and differential, with optimal threshold values of 3,000 WBC/μL and 80% polymorphonuclear cells, respectively…

15. Muscular fitness as a mediator of quality CPR

López-González A, et al. Am J Emerg Med. 2016 Sep;34(9):1845-9.

BACKGROUND: It has been hypothesized that body mass index (BMI) and muscle strength (MS) of the rescuers are predictors of adequate external chest compressions (ECC). The aims of this study were: (a) to analyze, in college students, the relationship between BMI and MS with adequate ECC parameters; and (b) to examine whether the association between BMI and adequate ECC parameters is mediated by MS.

METHODS: A cross-sectional analysis of the evaluation of a CPR performance test involving students (n=63). We determined BMI and MS. After previous training, participants performed cardiopulmonary resuscitation on a mannequin for 20 minutes. PROCESS macro developed by Preacher and Hayes was used to assess whether the association between BMI and ECC was mediated by MS.

RESULTS: Underweight subjects achieved lower results than those with normal weight and overweight/obese in several dependent variables including: correct compression depth (P less than .001) and adequate ECC (P less than .001). This differences remained after adjusting for muscle strength except for the compression rate (P=.053). Moreover, participants in the low MS quartile were lower in both correct compression depth (P=.001) and adequate ECC (P less than .001) than participants in the medium/high quartile after adjusting for confounding variables. The effect of BMI on adequate ECC was partially mediated by MS. Similar results were obtained in the analysis of the mediator role of MS in the relationship between BMI and correct compression depth.

CONCLUSIONS: The ability to provide adequate ECC is influenced by the rescuer's MS. Rescuers should be advised to exercise arm strength to improve the quality of CPR.

16. Updated Guidelines for Antiretroviral PEP after Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016

Centers for Disease Control and Prevention. Ann Emerg Med. 2016;98(3):335-338.

The purpose of these guidelines is to provide health care providers in the United States with updated guidelines to the 2005 US Department of Health and Human Services nonoccupational postexposure prophylaxis (nPEP) recommendations1 on the use of antiretroviral nPEP and other aspects of case management for persons with isolated exposure outside health care settings to blood, genital secretions, or other potentially infectious body fluids that might contain HIV. The use of occupational postexposure prophylaxis for case management for persons with possible HIV exposures occurring in health care settings is not addressed in this guideline; updated occupational postexposure prophylaxis guidelines have been published separately.2

This update incorporates additional evidence about use of nPEP from animal studies and human observational studies, and consideration of new antiretroviral medications that were approved since the 2005 guidelines, some of which have improved tolerability. New features are inclusion of guidelines for the use of rapid antigen-antibody combination HIV tests, for revised preferred and alternative 3-drug antiretroviral nPEP regimens, an updated schedule of laboratory evaluations of source and exposed persons, updated antimicrobial regimens for prophylaxis of sexually transmitted infections and hepatitis, and a suggested procedure for transitioning patients between nPEP and HIV preexposure prophylaxis, as appropriate…

17. Validation of the "Step-by-Step" Approach in the Management of Young Febrile Infants.

Gomez B, et al. Pediatrics. 2016 Aug;138(2).

BACKGROUND: A sequential approach to young febrile infants on the basis of clinical and laboratory parameters, including procalcitonin, was recently described as an accurate tool in identifying patients at risk for invasive bacterial infection (IBI). Our aim was to prospectively validate the Step-by-Step approach and compare it with the Rochester criteria and the Lab-score.

METHODS: Prospective study including infants ≤90 days with fever without source presenting in 11 European pediatric emergency departments between September 2012 and August 2014. The accuracy of the Step-by-Step approach, the Rochester criteria, and the Lab-score in identifying patients at low risk of IBI (isolation of a bacterial pathogen in a blood or cerebrospinal fluid culture) was compared.

RESULTS: Eighty-seven of 2185 infants (4.0%) were diagnosed with an IBI. The prevalence of IBI was significantly higher in infants classified as high risk or intermediate risk according to the Step by Step than in low risk patients. Sensitivity and negative predictive value for ruling out an IBI were 92.0% and 99.3% for the Step by Step, 81.6% and 98.3% for the Rochester criteria, and 59.8% and 98.1% for the Lab-score. Seven infants with an IBI were misclassified by the Step by Step, 16 by Rochester criteria, and 35 by the Lab-score.

CONCLUSIONS: We validated the Step by Step as a valuable tool for the management of infants with fever without source in the emergency department and confirmed its superior accuracy in identifying patients at low risk of IBI, compared with the Rochester criteria and the Lab-score.

18. Prevalence and Localization of PE in Unexplained Acute Exacerbations of COPD: A systematic review and meta-analysis.

Aleva FE, et al. Chest. 2016 Aug 11 [Epub ahead of print]

BACKGROUND: COPD patients encounter episodes of increased inflammation, so-called acute exacerbations of COPD (AE-COPD). In 30% of AE-COPD no clear etiology is found. Since there is a well-known crosstalk between inflammation and thrombosis, the objectives of this study were to determine the prevalence, embolus localization and clinical relevance, and clinical markers of pulmonary embolism (PE) in unexplained AE-COPD.

METHODS: A systematic search was performed using MEDLINE and EMBASE platforms from 1974 - October 2015. Prospective- and cross-sectional studies that included patients with an AE-COPD and used pulmonary CT-angiography for diagnosis of PE were included.

RESULTS: The systematic search resulted in 1650 records. Main reports of 22 articles were reviewed and 7 studies were included. The pooled prevalence of PE in unexplained AE-COPD was 16.1% (95% confidence-interval 8.3%-25.8%) in a total of 880 patients. Sixty-eight percent of the emboli found were located in the main pulmonary arteries, lobar arteries or inter-lobar arteries. Mortality and length of hospital admission seem to be increased in patients with unexplained AE-COPD and PE. Pleuritic chest pain and cardiac failure were more frequently reported in patients with unexplained AE-COPD and PE. In contrast, signs of respiratory tract infection was less frequently related to PE.

CONCLUSIONS: PE is frequently seen in unexplained AE-COPD. Two-thirds of emboli are found at localizations that have a clear indication for anticoagulant treatment. These findings merit clinical attention. PE should receive increased awareness in patients with unexplained AE-COPD, especially when pleuritic chest pain and signs of cardiac failure are present and no clear infectious origin can be identified.

19. Physicians, Patients, and Firearms 

A. Yes, You Can: Physicians, Patients, and Firearms 

Wintemute GJ, et al. Ann Intern Med.  2016;165(3):205-213.

Physicians have unique opportunities to help prevent firearm violence. Concern has developed that federal and state laws or regulations prohibit physicians from asking or counseling patients about firearms and disclosing patient information about firearms to others, even when threats to health and safety may be involved. This is not the case. In this article, the authors explain the statutes in question, emphasizing that physicians may ask about firearms (with rare exceptions), may counsel about firearms as they do about other health matters, and may disclose information to third parties when necessary. The authors then review circumstances under which questions about firearms might be most appropriate if they are not asked routinely. Such circumstances include instances when the patient provides information or exhibits behavior suggesting an acutely increased risk for violence, whether to himself or others, or when the patient possesses other individual-level risk factors for violence, such as alcohol abuse.

The article summarizes the literature on current physician practices in asking and counseling about firearms, which are done far less commonly than recommended. Barriers to engaging in those practices, the effectiveness of clinical efforts to prevent firearm-related injuries, and what patients think about such efforts and physicians who engage in them are discussed. Proceeding from the limited available evidence, the authors make specific recommendations on how physicians might counsel their patients to reduce their risk for firearm-related death or serious injury. Finally, the authors review the circumstances under which disclosure of patient information about firearms to third parties is supported by regulations implementing the Health Insurance Portability and Accountability Act…

The remainder of the essay, full-text (free): http://annals.org/article.aspx?articleid=2522436

B. Curbing Firearm Violence: Identifying a Specific Target for Physician Action

Weinberger SE.  Ann Intern Med.  2016;165(3):221-222.

Physicians not only have a responsibility to their patients to diagnose and treat illness; they also have a broader societal obligation to improve population health. The latter can be discharged in part through activities and conversations with patients and families aimed at primary prevention of illness and injury. We have witnessed many examples of successful public health efforts focused on preventing illness and injury, such as immunization, use of seat belts, and smoking cessation initiatives. In each case, physicians and other health care providers have used various methods to inform and educate their patients and the public at large to effect changes in behavior and adoption of important preventive measures.

Many in the medical and public health communities have been attempting to raise consciousness about firearm-related violence as a similar public health problem that deserves action by health care professionals to reduce its magnitude and impact (1–4). Seven large and influential medical professional societies—the American College of Physicians (ACP), the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Surgeons, the American College of Obstetricians and Gynecologists, the American Psychiatric Association, and the American College of Emergency Physicians—have joined with the American Public Health Association to issue a “call to action” to address firearm-related violence as a major public health problem (5). The American Bar Association (ABA) also partnered in this effort, noting that none of the recommendations presented by these health professional organizations violated the Second Amendment, as established by Supreme Court decisions. Among these recommendations is a halt to physician gag laws that are intended to forbid physicians from discussing a patient's gun ownership and attempting to mitigate the associated risk. More than 50 organizations have now endorsed the positions and recommendations espoused in this call-to-action paper (6)…

The remainder of the essay, full-text (free): http://annals.org/article.aspx?articleid=2523533

20. Association of Acetaminophen Use during Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding.

Stergiakouli E, et al. JAMA Pediatr. 2016 Aug 15 [Epub ahead of print]

Importance: Acetaminophen (paracetamol) is used by a large proportion of pregnant women. Research suggests that acetaminophen use in pregnancy is associated with abnormal fetal neurodevelopment. However, it is possible that this association might be confounded by unmeasured behavioral factors linked to acetaminophen use.

Objective: To examine associations between offspring behavioral problems and (1) maternal prenatal acetaminophen use, (2) maternal postnatal acetaminophen use, and (3) partner's acetaminophen use.

Design, Setting, and Participants: From February 2015 to March 2016, we collected and analyzed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort. We studied 7796 mothers enrolled in ALSPAC between 1991 and 1992 along with their children and partners.

Exposures: Acetaminophen use was assessed by questionnaire completion at 18 and 32 weeks of pregnancy and when the child was 61 months old.

Main Outcomes and Measures: Maternal reports of behavioral problems using the Strengths and Difficulties Questionnaire (SDQ) when the children were 7 years old. We estimated risk ratios for behavioral problems in children after prenatal, postnatal, and partner's exposure to acetaminophen and mutually adjusted each association.

Results: Maternal prenatal acetaminophen use at 18 (n = 4415; 53%) and 32 weeks of pregnancy (n = 3381; 42%) was associated with higher odds of having conduct problems (risk ratio [RR], 1.42; 95% CI, 1.25-1.62) and hyperactivity symptoms (RR, 1.31; 95% CI, 1.16-1.49), while maternal acetaminophen use at 32 weeks was also associated with higher odds of having emotional symptoms (RR, 1.29; 95% CI, 1.09-1.53) and total difficulties (RR, 1.46; 95% CI, 1.21-1.77). This was not the case for maternal postnatal (n = 6916; 89%) or partner's (n = 3454; 84%) acetaminophen use. We found the associations between maternal prenatal acetaminophen use and all the SDQ domains unchanged even after adjusting for maternal postnatal or partner's acetaminophen use.

Conclusions and Relevance: Children exposed to acetaminophen prenatally are at increased risk of multiple behavioral difficulties, and the associations do not appear to be explained by unmeasured behavioral or social factors linked to acetaminophen use insofar as they are not observed for postnatal or partner's acetaminophen use. Although these results could have implications for public health advice, further studies are required to replicate the findings and to understand mechanisms.

21. Less is More: Redefining Balance

By Christina Shenvi, MD, PHD. EP Monthly, AUGUST 3, 2016

Want a better work/life balance? Hint – it’s not about being better at multitasking.

I am tired of hearing about balance. We talk about it, we go to lectures on it, we give mandatory presentations on it to our interns. Yet few people would say they have actually achieved this elusive, zen state. In fact, more than 70% of ER doctors have signs of burn-out [1] – the opposite of balance. Too many presentations on balance give insipid suggestions to “make sure you exercise and eat well,” or “find time to sleep.” I can’t imagine that advice would be very helpful to someone who is already burning out and living in the margins of their free time and energy. Something is wrong with this picture.

First of all, let’s look at the language we use. We all talk about “finding” balance. Where did it go? Did we lose it? Did we used to have it? I imagine that we did used to have balance. Perhaps it was when we were in college, or in medical school. Maybe it ended when residency started, or perhaps when we started having kids. At some point, we jumped onto a treadmill called ‘career’. We ambled along, excited at our new position. Then that treadmill started to move a little faster. If you had a kid or four, then it felt like running on the treadmill carrying the kids with you.

We are all constantly adding more to our work lives, taking on new responsibilities, chairing new committees, stepping into new leadership roles. All the while we are trying to keep the peace at home with our spouses and children, stay active, and still maintain some vestige of our former hobbies. (Hobbies you ask? Those were those things we used to do for fun before we had busy jobs and busy families, like rock climbing, crocheting, or peeing without little humans storming the bathroom door.)

If you are like me, you have started to notice signs of burnout. The struggle is real. At work we have to take care of difficult and violent patients, meet core measures, chart, and deal with patient complaints. After our shift ends we come home to kids, errands, bills, and all the household stuff, like cooking something other than grilled cheese for dinner. I hear these refrains day after day, yet we all still seek this elusive thing called balance, as though we were in search of a mystical unicorn that we’ll never find.

Why have we arrived at this state of perpetual imbalance? What can we do to start to reclaim our own wellness and find this mysterious balance? Here are some suggestions, not from someone who has figured it all out, but as someone who is in the thick of it, striving to do better.

Redefine balance
Balance should not be seen as ’doing it all’. A balanced life does not mean being in five different leadership roles at work while also coaching your kid’s soccer team, sewing hand-made Halloween costumes and growing your own organic vegetables. If we define balance as doing everything and doing it well, we are bound to fail. Perhaps we should define balance as living a life that meets your own personal goals, understanding that there will have to be compromise. Your ideal life may look like 12-hour workdays, and frequent travel in order to reach further leadership positions at work. Someone else’s might look like working part time and spending more time with kids, or working close to quarter-time to have time to homeschool. We need to define what our own personal goals are, and then try to bring our lives more into alignment with them. Now obviously, we can’t define away doing medical charts, or define a higher salary for ourselves. There are financial realities and time constraints we have to deal with. We need to figure out what we want and what is negotiable in terms of hours, responsibility, pay, and time. When the pie chart of what you are actually doing matches the pie chart of your priorities – that is balance.

Choose what brings you joy
Ask yourself what floats your boat? What gets you up in the morning (figuratively, not what actually gets you up, which is probably a loud alarm, children, and coffee)? It is easy to say yes to so many things that crowd out what you really love. That one committee that will meet once a month? Reviewing a paper? Giving a lecture? These are all good things. But they can easily squeeze away the time we have for more important things. If it is something you love and are passionate about, then do it! If it is something that you have no choice about and have to do in order to meet your other goals that you are passionate about, then do it! If you don’t really want to, and you don’t have to, then say no. Those little things can add up and tip your balance. You are not a super hero with inhuman strength or stamina. Give yourself permission to say no to things. Cull what drags you down, and focus on the things that you love, both at work and at home…

22. Intraosseous access in the obese patient: assessing the need for extended needle length.

Kehrl T, et al. Am J Emerg Med. 2016 Sep;34(9):1831-4.

BACKGROUND: Intraosseous (IO) access can be complicated by obesity. Successful placement of a 25 mm IO needle is unlikely when soft tissue depth exceeds 20 mm.

OBJECTIVES: The authors examined the relationship between body mass index (BMI), the ability to palpate the tibial tuberosity (TT), and soft tissue depth at recommended IO insertion sites.

METHODS: Obese emergency department patients were assessed for a palpable TT and received ultrasound measurement of the soft tissue depth at recommended IO insertion sites. Linear and logistic regression were used to determine cut-off BMI values predicting soft tissue depth greater than 20 mm.

RESULTS: Seventy-five patients were enrolled with a mean BMI of 47.2. The mean soft tissue depth at the proximal humerus, proximal tibial, and distal tibial were 29.6 [95% CI 27.5-31.7] mm, 11.0 [8.9-13.0] mm, and 10.7 [9.4-12.1] mm, respectively. In 5 patients without a palpable TT the soft tissue depth exceeded 20 mm at all three anatomic sites. A BMI ≥43 and BMI ≥60 predicted a soft tissue depth greater than 20 mm at the proximal tibia and distal tibia, respectively, while no reliable BMI cut-off was identified at the proximal humerus.

CONCLUSIONS: In obese adults with a palpable TT or BMI ≤43 a 25 mm IO needle is likely adequate at the proximal and distal tibial insertion sites. Empiric use of an extended 45 mm IO needle is advisable at the proximal humeral insertion site in obese patients.

23. Interactive Medical Case from the NEJM

A 19-year-old woman presented to the ED with abdominal pain in the right upper quadrant that had been progressively worsening for the past 2 days. She reported a 3-month history of intermittent abdominal pain that caused what she described as a "pressure-like" sensation. This pain was nonradiating and was unrelated to food intake or bowel movements. The pain was associated with…

24. Micro Bits

A. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children

The Amish and the Hutterites are farming communities with similar gene pools, but asthma and allergy are more common in Hutterites. The authors provide data that support the idea that the Amish environment stimulates the innate immune response and protects the children from asthma.

B. Fire-Related Inhalation Injury

Fire-related inhalation injury results from a combination of direct exposures, systemic effects of inhaled toxins, accrual of endobronchial debris, and secondary infection. This brief review discusses the pathogenesis of and approach to fire-related inhalation injury.

Full-text (requires subscription): http://www.nejm.org/doi/full/10.1056/NEJMra1601128

C. Changes in the Leading Cause of Death: Recent Patterns in Heart Disease and Cancer Mortality

The mortality burden of cancer has surpassed that of heart disease in several states. In 2000, there were only 2 states where cancer was the leading cause of death; in 2014, there were 22.

Heart disease remained the leading cause of death for the non-Hispanic white and non-Hispanic black populations in 2014.

Cancer is now the leading cause of death for the non-Hispanic Asian or Pacific Islander and Hispanic populations. The timing of the leading-cause crossover varied by group.

D. Nicer neighborhoods get creepier crawlies

Science News. By Jessica Boddy. Aug. 2, 2016

When you’re rich, you can have more of everything—more opportunities for travel, more flashy gadgets, more house, and now, something else: more bugs. A new study suggests that people in affluent neighborhoods have a richer variety of arthropods in their homes, something they call the “luxury effect.” It works like this: People in wealthy zip codes tend to have more extensive landscaping with a greater variety of plant species. That means, in turn, that the arthropods they attract—creepy crawlies including spiders, flies, and millipedes—are also more diverse. To see whether this idea had legs, a team of entomologists strapped on kneepads and headlamps and scoured 50 different homes in Raleigh for any arthropod they could find. They collected 10,000 specimens from more than 300 different families, from the humble pill bug to the panic-inducing paper wasp. (Other species they collected are in the slideshow above.) They found that houses in neighborhoods with the highest average incomes had more species than those in the lowest income bracket, they report today in Biology Letters….

E. Survey: Many physicians are not saving enough for retirement

Almost 40% of some 125,000 practicing physicians surveyed said they were behind on their retirement savings, according to a study from American Medical Association Insurance. However, the study also found that from 2013 to 2016, the number of physicians ahead of schedule on retirement savings increased from 6% to 11%.

F. Obesity is strong risk factor for heart failure, study finds

Obesity, especially severe obesity, has a strong link to heart failure that is unexplained by traditional risk factors, researchers reported in the Journal of the American Heart Association. The study found obesity was a bigger factor for heart failure than for other cardiovascular diseases, and researchers said weight loss is critical for heart failure prevention.

G. Suicide-Prone Occupations: Farming more dangerous than Library Services says the CDC

A snapshot of suicide reports from 17 states has shown that people working in farming, fishing, and forestry jobs took their own lives at the highest rate among 22 occupation categories studied.

H. Antibiotics in the first 2 years of life and weight development

Alterations in the gut microbiome have been documented to affect body weight. Although previous studies have shown that early antibiotic exposure may affect weight development, the effects of antibiotic class and timing of exposure are unknown. This study examined the influence of timing of antibiotic exposure, type of antibiotics used, and number of exposures on height and weight development up to 10 years of age. Increased weight and height z-scores were observed in children exposed to one course of antibiotics in the first 6 months of life and in children with two or more courses during the second year of life. These associations were mainly seen in exposure to broad- and narrow-spectrum β-lactams. Exposure later in life was not associated with anthropometric outcomes. If causality of obesity can be established in the future, this illustrates the need for judicious antibiotic use early in life.

I. The CDC Speaks Out on Sepsis

J. New app helps doctors respond to in-flight emergencies

If you're unlucky enough to be one of the 150 to 200 people each day who have a medical emergency on an airplane, your care is in the hands of whatever medical professionals happen to be among your fellow passengers. The chances are they're not emergency physicians and they haven't trained for this particular eventuality.

"When doctors are up in the air, they really are not familiar with the environment," Dr. Raymond E. Bertino, a clinical professor of radiology and surgery at the University of Illinois College of Medicine, who has found himself in three such emergencies -- twice as a doctor and once as a patient -- told MobiHealthNews. "Most of them are not emergency doctors. You might have a radiologist, you might have a pediatrician, you might have an OB doctor, who really doesn’t know how to deal with emergencies in a day to day way. But the truth of the matter is, there’s not that many things that can be done up in the air. There’s some things that are very important, but they’re things that anybody with medical training can handle as long as they know what to do and remember what to do."

K. Flossing not included in dietary guidelines

The USDA's Dietary Guidelines for Americans do not contain a recommendation that people floss their teeth, and a report found a lack of scientific evidence to support flossing for good oral health. AAFP Board Chair Robert Wergin, M.D., said although there is a lack of evidence to support flossing, there also is "not much of a downside" and cleaning between the teeth is an important part of oral health, which affects overall health.

L. Study links time spent watching TV to risk of pulmonary embolism

A study in the journal Circulation found TV watching for 2.5 hours to five hours per day increased the risk of a fatal blood clot by 70%, while more than five hours daily increased the risk by 250%. Japanese researchers said the risk was independent of physical exercise.