Thursday, February 06, 2014

Lit Bits: Feb 6, 2014

From the recent medical literature...

1. Off-hour presentation and outcomes in patients with acute myocardial infarction: systematic review and meta-analysis 

Sorita A, et al. BMJ 2014;348:f7393  

Objective To assess the association between off-hour (weekends and nights) presentation, door to balloon times, and mortality in patients with acute myocardial infarction. 

Data sources Medline in-process and other non-indexed citations, Medline, Embase, Cochrane Database of Systematic Reviews, and Scopus through April 2013. 

Study selection Any study that evaluated the association between time of presentation to a healthcare facility and mortality or door to balloon times among patients with acute myocardial infarction was included. 

Data extraction Studies’ characteristics and outcomes data were extracted. Quality of studies was assessed with the Newcastle-Ottawa scale. A random effect meta-analysis model was applied. Heterogeneity was assessed using the Q statistic and I2. 

Results 48 studies with fair quality, enrolling 1 896 859 patients, were included in the meta-analysis. 36 studies reported mortality outcomes for 1 892 424 patients with acute myocardial infarction, and 30 studies reported door to balloon times for 70 534 patients with ST elevation myocardial infarction (STEMI). Off-hour presentation for patients with acute myocardial infarction was associated with higher short term mortality (odds ratio 1.06, 95% confidence interval 1.04 to 1.09). Patients with STEMI presenting during off-hours were less likely to receive percutaneous coronary intervention within 90 minutes (odds ratio 0.40, 0.35 to 0.45) and had longer door to balloon time by 14.8 (95% confidence interval 10.7 to 19.0) minutes. A diagnosis of STEMI and countries outside North America were associated with larger increase in mortality during off-hours. Differences in mortality between off-hours and regular hours have increased in recent years. Analyses were associated with statistical heterogeneity. 

Conclusion This systematic review suggests that patients with acute myocardial infarction presenting during off-hours have higher mortality, and patients with STEMI have longer door to balloon times. Clinical performance measures may need to account for differences arising from time of presentation to a healthcare facility. 

2. ER Briefs: Open Season on ACEP tPA Guidelines 

By Elbert Chu. Medpage Today, Jan 29, 2014 | Updated: Jan 30, 2014 

Some medical guidelines arrive barely noticed, but others -- say, last fall's new AHA/ACC guidelines for managing cholesterol -- lead to a ruckus. That's what happened with a 2013 guideline from the American College of Emergency Physicians (ACEP) that all but backed intravenous clot buster thrombolytics for acute ischemic stroke. 

And last week, ACEP responded by declaring open season on those guidelines, launching a 60-day member comment period. 

There's a swirl of reasons why emergency physicians had concerns. WhiteCoat's Call Room put together an excellent rundown. Here's a condensed version:

1. Evidence inconclusive? An independent review of 12 plasminogen activator (tPA) studies failed to reveal conclusive evidence for or against use in ischemic stroke, even as its use rises at primary stroke centers.

2. Author bias? The BMJ pointed out that almost all the guideline authors had links to thrombolytic manufacturers and, perhaps more damning, noted inadequate disclosures in some cases.

3. Behind closed doors? The ACEP did not give its members an opportunity to review or comment on the draft guidelines before they were published.

4. Malpractice bait? ACEP bestowed a "Level A" ranking on the guidelines, effectively elevating tPA to standard of care status -- and giving plaintiffs' attorneys fodder for suits against physicians who select other treatment for acute ischemic stroke. 

So why now? 

"The crux of the issue deals with a debate of methodology and academic rigor required for a Level A recommendation and whether these particular meta-analyses provided sufficient evidence," Howard Mell, MD, a spokesperson for ACEP, told MedPage Today. 

Mell added that the experience had prompted ACEP to revise its guideline review process -- which previously only included experts and other related organizations -- to include member comment. 

Regarding conflict of interest issues, ACEP said that it reviewed all the disclosure statements and that "perceived conflicts were managed appropriately." Mell said, "At no point has anyone in leadership entertained the idea that the recommendations were at the paid behest of industry." 

Undecided on the tPA/Alteplase issue? Check out the entertaining and data-packed "tPA Cage Match" video below recorded at the EMCrit/ISMMS conference that featured pro-tPA doc Andy Jagoda, MD, chair of the department of emergency medicine at Mount Sinai and past chair of ACEP in one corner. The real action starts at 5 minutes. 

In the other corner, arguing against the guidelines, Anand Swaminathan, MD, MPH, assistant professor of emergency medicine at New York University Medical Center and assistant residency director at Bellevue. Swaminathan (who also writes over at EM Lyceum) posted a thorough piece, if you'd rather read than watch. Swaminathan's slam starts around 19 minutes. 

We reached out to Swaminathan for his take on three questions about the ACEP guidelines. See why he says the Level A recommendations are  "fraught" with problems. 

Have a comment and "supporting evidence" to add? Head over to the ACEP site between now and March 24th. Though your comments won't be posted online, as WhiteCoat Call Room points out, submissions will only be shared with the board. 

Full-text (free), with links to essays and videos:  

3. Updated ACEP Procedural Sedation Guidelines  

Fesmire FM, et al. Ann Emerg Med. 2014;63:247-258. 

This clinical policy from the American College of Emergency Physicians is the revision of a 2005 clinical policy evaluating critical questions related to procedural sedation in the emergency department. A writing subcommittee reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions:

(1) In patients undergoing procedural sedation and analgesia in the emergency department, does preprocedural fasting demonstrate a reduction in the risk of emesis or aspiration?

(2) In patients undergoing procedural sedation and analgesia in the emergency department, does the routine use of capnography reduce the incidence of adverse respiratory events?

(3) In patients undergoing procedural sedation and analgesia in the emergency department, what is the minimum number of personnel necessary to manage complications?

(4) In patients undergoing procedural sedation and analgesia in the emergency department, can ketamine, propofol, etomidate, dexmedetomidine, alfentanil and remifentanil be safely administered?

A literature search was performed, the evidence was graded, and recommendations were given based on the strength of the available data in the medical literature. 

4. Pediatric Weight Estimates: Which Method Is Best? 

In this large Australian study, the Best Guess formula was the most accurate for predicting weight in children older than 1 year. 

Graves L, et al. A comparison of actual to estimated weights in Australian children attending a tertiary children's' hospital, using the original and updated APLS, Luscombe and Owens, Best Guess formulae and the Broselow tape. Resuscitation. 2013 Dec 7. [Epub ahead of print] 

INTRODUCTION: During paediatric resuscitation it is essential to be able to estimate the child's weight as it determines drug doses and equipment sizes. Age and length-based estimations exist, with age-based estimations being especially useful in the preparation phase and the length-based Broselow tape having weight-based drug doses and equipment already assigned via a colour code system. The aim of this study was to compare the actual recorded weights of Australian children to the predicted weights using the original and updated APLS, Luscombe and Owens and Best Guess formulae and the Broselow tape. 

METHOD: A retrospective observational study of children attending an Australian tertiary children's hospital. 

RESULTS: From 49,565 patients extracted from the database, 37,114 children with age and weight and 37,091 children with age and height recorded were included in the analysis. Best Guess was the most accurate, with the smallest overall mean difference 0.86kg. For those under 1 year old, Broselow tape was the most accurate (mean difference -0.43kg), Best Guess was the most accurate for ages 1-5 years and 11-14 years (mean difference 0.27 and 0.20kg respectively), and the updated APLS formula was the most accurate for 6-10 year-old (mean difference 0.42kg). The Broselow tape was able to only classify 48.9% of children into the correct weight colour band. 

CONCLUSIONS: For an age-based weight estimation, in infants less than one year the new APLS formula is the most accurate and over one year the Best Guess formulae should be used. 

5. The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran 

Alikhan R, et al. Emerg Med J  2014;31:163-168   

Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not ‘routine’.  

The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma.  

If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment.  

If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s). 

See these related articles:

Fawole A, et al. Practical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixaban. Cleve Clin J Med. 2013;80(7):443-51. Full-text (free):   

Pollack CV Jr. Managing bleeding in anticoagulated patients in the emergency care setting. J Emerg Med. 2013;45(3):467-77.   

6. An electronic order set for AMI is associated with improved patient outcomes through better adherence to clinical practice guidelines. 

Ballesca MA, et al. J Hosp Med. 2014 Feb 3. [Epub ahead of print] 

BACKGROUND: Adherence to evidence-based recommendations for acute myocardial infarction (AMI) remains unsatisfactory. 

OBJECTIVE: Quantifying association between using an electronic AMI order set (AMI-OS) and hospital processes and outcomes. 

DESIGN: Retrospective cohort study. 

SETTING: Twenty-one community hospitals. 

PATIENTS: A total of 5879 AMI patients were hospitalized between September 28, 2008 and December 31, 2010. 

MEASUREMENTS: We ascertained whether patients were treated using the AMI-OS or individual orders (a la carte). Dependent process variables were use of evidence-based care; outcome variables were mortality and rehospitalization. 

RESULTS: Use of individual and combined therapies improved outcomes (eg, 50% lower odds of 30-day mortality for patients with ≥3 therapies). The 3531 patients treated using the AMI-OS were more likely to receive evidence-based therapies (eg, 50% received 5 different therapies vs 36% a la carte). These patients had lower 30-day mortality (5.7% vs 8.5%) than the 2348 treated using a la carte orders. Although AMI-OS patients' predicted mortality risk was lower (3.2%) than that of a la carte patients (4.8%), the association of improved processes and outcomes with the use of the AMI-OS persisted after risk adjustment. For example, after inverse probability weighting, the relative risk for inpatient mortality in the AMI-OS group was 0.67 (95% confidence interval: 0.52-0.86). Inclusion of use of recommended therapies in risk adjustment eliminated the benefit of the AMI-OS, highlighting its mediating effect on adherence to evidence-based treatment. 

CONCLUSIONS: Use of an electronic order set is associated with increased adherence to evidence-based care and better AMI outcomes. 

7. New American Academy of Pediatrics Guidelines 

A. Updated guidelines advise on assessing fractures for child abuse  

Certain child fractures, such as rib and scapula fractures, are strongly linked to physical abuse, particularly among infants, according to the American Academy of Pediatrics' clinical report published in the journal Pediatrics. The group said a child's age, medical history, other injuries, and the location, type and mechanism of fracture must be evaluated to determine if injuries are caused by physical abuse. 

Fractures are common injuries caused by child abuse. Although the consequences of failing to diagnose an abusive injury in a child can be grave, incorrectly diagnosing child abuse in a child whose fractures have another etiology can be distressing for a family. The aim of this report is to review recent advances in the understanding of fracture specificity, the mechanism of fractures, and other medical diseases that predispose to fractures in infants and children. This clinical report will aid physicians in developing an evidence-based differential diagnosis and performing the appropriate evaluation when assessing a child with fractures. 

B. Management of Dental Trauma in a Primary Care Setting 

The American Academy of Pediatrics and its Section on Oral Health have developed this clinical report for pediatricians and primary care physicians regarding the diagnosis, evaluation, and management of dental trauma in children aged 1 to 21 years. This report was developed through a comprehensive search and analysis of the medical and dental literature and expert consensus. Guidelines published and updated by the International Association of Dental Traumatology ( are an excellent resource for both dental and nondental health care providers. 

8. INR Is Not an Accurate Predictor of Coagulopathy in Trauma Patients  

Richard D. Zane, Journal Watch Emergency Medicine.   

Thromboelastography is a better predictor and is more clinically relevant.  

The international normalized ratio (INR) is measured routinely in trauma patients and is commonly used as a measurement of coagulopathy and a guide for the administration of fresh frozen plasma (FFP). Thromboelastography is a point-of-care coagulation assay that uses the time-dependent viscoelastic properties of whole blood to provide an assessment of clotting ability; it is considered more clinically relevant than INR.  

In this prospective observational study of 106 adult hemodynamically stable surgical and trauma patients receiving FFP, researchers measured thromboelastography values, clotting factor levels, and INRs before and after FFP infusion. FFP was administered based on the attending surgeon's discretion.  

Administration of FFP significantly decreased the median INR (from 1.87 to 1.53), but did not change thromboelastography values or clotting factor levels, all of which remained normal. 

Comment: INR is not a clinically relevant predictor of coagulopathy in trauma patients and should not be used to assess coagulation status or guide administration of fresh frozen plasma. Clinical assessment of bleeding as well as transfusion requirement should continue to guide FFP administration. As thromboelastography becomes more available, it may have a role in guiding blood product use in the acute management of hemorrhage.  

Source: McCully SP et al. J Trauma Acute Care Surg 2013 Dec; 75:947. Abstract:   

9. Serotonin Syndrome: Consider in the Older Patient with AMS 

By Christina Shenvi, MD PhD | February 3rd, 2014 | ALiEM  

What’s the first thing that pops into your head when you see an older woman presenting to the ED from a nursing facility with atraumatic altered mental status? If you’re like me, ‘UTI’ comes quickly to mind. I then banish the thought of a UTI and force myself to go through a worst-first differential diagnosis to exclude, either through the history and clinical assessment or through testing, more dangerous causes. This is a case of a 67-year-old woman with an unusual cause of altered mental status… and a UTI. 

10. Images in Clinical Practice 

Acute Intermittent Porphyria

An Unusual Cause of Electrocardiographic ST Elevation- Can the Japanese Fishing Industry Help Us?

Ocular Manifestation of Electrical Burn 

11. Management of Febrile Neonates in US Pediatric EDs 

Jain S, et al. Pediatrics. 2014 Jan 27. [Epub ahead of print] 

What’s Known on This Subject
Recommended management of febrile neonates (≤28 days) includes blood, urine, and cerebrospinal fluid cultures with hospital admission for antibiotic therapy. No study has reported adherence to standard recommendations in the management of febrile neonates in US pediatric emergency departments.  

What This Study Adds
There is wide variation in adherence to recommended management of febrile neonates. High rates of serious infections in admitted patients but low return rates for missed infections in discharged patients suggest additional studies needed to understand variation from current recommendations. 

BACKGROUND: Blood, urine, and cerebrospinal fluid cultures and admission for antibiotics are considered standard management of febrile neonates (0–28 days). We examined variation in adherence to these recommendations across US pediatric emergency departments (PEDs) and incidence of serious infections (SIs) in febrile neonates.  

METHODS: Cross-sectional study of neonates with a diagnosis of fever evaluated in 36 PEDs in the 2010 Pediatric Health Information System database. We analyzed performance of recommended management (laboratory testing, antibiotic use, admission to hospital), 48-hour return visits to PED, and diagnoses of SI.  

RESULTS: Of 2253 neonates meeting study criteria, 369 (16.4%) were evaluated and discharged from the PED; 1884 (83.6%) were admitted. Recommended management occurred in 1497 of 2253 (66.4%; 95% confidence interval, 64.5–68.4) febrile neonates. There was more than twofold variation across the 36 PEDs in adherence to recommended management, recommended testing, and recommended treatment of febrile neonates. There was significant variation in testing and treatment between admitted and discharged neonates (P less than .001). A total of 269 in 2253 (11.9%) neonates had SI, of whom 223 (82.9%; 95% confidence interval, 77.9–86.9) received recommended management.  

CONCLUSIONS: There was wide variation across US PEDs in adherence to recommended management of febrile neonates. One in 6 febrile neonates was discharged from the PED; discharged patients were less likely to receive testing or antibiotic therapy than admitted patients. A majority of neonates with SI received recommended evaluation and management. High rates of SI in admitted patients but low return rates for missed infections in discharged patients suggest a need for additional studies to understand variation from the current recommendations. 

12. Two ACS Rules for Safe Expedited ED Discharge of Low Risk Pts 

A. Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol. 

Than M, et al. Emerg Med Australas. 2014 Jan 15. [Epub ahead of print] 

OBJECTIVE: Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED, saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol (ADP) that could safely increase the proportion of patients suitable for early discharge. 

METHODS: Logistic regression identified statistical predictors for major adverse cardiac events in a derivation cohort. Statistical coefficients were converted to whole numbers to create a score. Clinician feedback was used to improve the clinical plausibility and the usability of the final score (Emergency Department Assessment of Chest pain Score [EDACS]). EDACS was combined with electrocardiogram results and troponin results at 0 and 2 h to develop an ADP (EDACS-ADP). The score and EDACS-ADP were validated and tested for reproducibility in separate cohorts of patients.

RESULTS: In the derivation (n = 1974) and validation (n = 608) cohorts, the EDACS-ADP classified 42.2% (sensitivity 99.0%, specificity 49.9%) and 51.3% (sensitivity 100.0%, specificity 59.0%) as low risk of major adverse cardiac events, respectively. The intra-class correlation coefficient for categorisation of patients as low risk was 0.87. 

CONCLUSION: The EDACS-ADP identified approximately half of the patients presenting to the ED with possible cardiac chest pain as having low risk of short-term major adverse cardiac events, with high sensitivity. This is a significant improvement on similar, previously reported protocols. The EDACS-ADP is reproducible and has the potential to make considerable cost reductions to health systems. 

What’s this fancy new risk stratification tool? Full-text (free):  

B. The new Vancouver Chest Pain Rule using troponin as the only biomarker: an external validation study 

Cullen L, et al. Amer J Emerg Med. 2014;2:129-134.  

To externally evaluate the accuracy of the new Vancouver Chest Pain Rule and to assess the diagnostic accuracy using either sensitive or highly sensitive troponin assays. 

Prospectively collected data from 2 emergency departments (EDs) in Australia and New Zealand were analysed. Based on the new Vancouver Chest Pain Rule, low-risk patients were identified using electrocardiogram results, cardiac history, nitrate use, age, pain characteristics and troponin results at 2 hours after presentation. The primary outcome was 30-day diagnosis of acute coronary syndrome (ACS), including acute myocardial infarction, and unstable angina. Sensitivity, specificity, positive predictive values and negative predictive values were calculated to assess the accuracy of the new Vancouver Chest Pain Rule using either sensitive or highly sensitive troponin assay results.

Of the 1635 patients, 20.4% had an ACS diagnosis at 30 days. Using the highly sensitive troponin assay, 212 (13.0%) patients were eligible for early discharge with 3 patients (1.4%) diagnosed with ACS. Sensitivity was 99.1% (95% CI 97.4-99.7), specificity was 16.1 (95% CI 14.2-18.2), positive predictive values was 23.3 (95% CI 21.1-25.5) and negative predictive values was 98.6 (95% CI 95.9-99.5). The diagnostic accuracy of the rule was similar using the sensitive troponin assay. 

The new Vancouver Chest Pain Rule should be used for the identification of low risk patients presenting to EDs with symptoms of possible ACS, and will reduce the proportion of patients requiring lengthy assessment; however we recommend further outpatient investigation for coronary artery disease in patients identified as low risk. 

Original Vancouver CP Rule (using CK-MB):  

13. Effects of Immediate BP Reduction on Death and Major Disability in Patients with Acute Ischemic Stroke: The CATIS RCT

He J, et al. JAMA. 2014;311(5):479-489.  

Importance  Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. 

Objective  To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. 

Design, Setting, and Participants  The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. 

Interventions  Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033).

Main Outcomes and Measures  Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge. 

Results  Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (−12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (−7.2%) in the control group within 24 hours after randomization (difference, −5.5% [95% CI, −4.9 to −6.1%]; absolute difference, −9.1 mm Hg [95% CI, −10.2 to −8.1]; P  less than  .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, −9.3 mm Hg [95% CI, −10.1 to −8.4]; P  less than  .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93).

Conclusion and Relevance  Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. 

14. Intussusception Risk Slightly Increases after Rotavirus Immunization

A. Risk of Intussusception after Monovalent Rotavirus Vaccination 

Weintraub ES, et al. N Engl J Med 2014; 370:513-519  

Although current rotavirus vaccines were not associated with an increased risk of intussusception in large trials before licensure, recent postlicensure data from international settings suggest the possibility of a small increase in risk of intussusception after monovalent rotavirus vaccination. We examined this risk in a population in the United States. 

Participants were infants between the ages of 4 and 34 weeks who were enrolled in six integrated health care organizations in the Vaccine Safety Datalink (VSD) project. We reviewed medical records and visits for intussusception within 7 days after monovalent rotavirus vaccination from April 2008 through March 2013. Using sequential analyses, we then compared the risk of intussusception among children receiving monovalent rotavirus vaccine with historical background rates. We further compared the risk after monovalent rotavirus vaccination with the risk in a concurrent cohort of infants who received the pentavalent rotavirus vaccine. 

During the study period, 207,955 doses of monovalent rotavirus vaccine (including 115,908 first doses and 92,047 second doses) were administered in the VSD population. We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine. For the two doses combined, the expected number of intussusception cases was 0.72, resulting in a significant relative risk of 8.4. For the pentavalent rotavirus vaccine, 1,301,810 doses were administered during the study period, with 8 observed intussusception cases (7.11 expected), for a nonsignificant relative risk of 1.1. The relative risk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination, as compared with the risk after pentavalent rotavirus vaccination, was 9.4 (95% confidence interval, 1.4 to 103.8). The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 5.3 per 100,000 infants vaccinated. 

In this prospective postlicensure study of more than 200,000 doses of monovalent rotavirus vaccine, we observed a significant increase in the rate of intussusception after vaccination, a risk that must be weighed against the benefits of preventing rotavirus-associated illness. (Funded by the Centers for Disease Control and Prevention.) 

B. Intussusception Risk after Rotavirus Vaccination in U.S. Infants 

Yih WK, et al. N Engl J Med 2014; 370:503-512  

International postlicensure studies have identified an increased risk of intussusception after vaccination with the second-generation rotavirus vaccines RotaTeq (RV5, a pentavalent vaccine) and Rotarix (RV1, a monovalent vaccine). We studied this association among infants in the United States. 

The study included data from infants 5.0 to 36.9 weeks of age who were enrolled in three U.S. health plans that participate in the Mini-Sentinel program sponsored by the Food and Drug Administration. Potential cases of intussusception and vaccine exposures from 2004 through mid-2011 were identified through procedural and diagnostic codes. Medical records were reviewed to confirm the occurrence of intussusception and the status with respect to rotavirus vaccination. The primary analysis used a self-controlled risk-interval design that included only vaccinated children. The secondary analysis used a cohort design that included exposed and unexposed person-time. 

The analyses included 507,874 first doses and 1,277,556 total doses of RV5 and 53,638 first doses and 103,098 total doses of RV1. The statistical power for the analysis of RV1 was lower than that for the analysis of RV5. The number of excess cases of intussusception per 100,000 recipients of the first dose of RV5 was significantly elevated, both in the primary analysis (attributable risk, 1.1 [95% confidence interval, 0.3 to 2.7] for the 7-day risk window and 1.5 [95% CI, 0.2 to 3.2] for the 21-day risk window) and in the secondary analysis (attributable risk, 1.2 [95% CI, 0.2 to 3.2] for the 21-day risk window). No significant increase in risk was seen after dose 2 or 3. The results with respect to the primary analysis of RV1 were not significant, but the secondary analysis showed a significant risk after dose 2. 

RV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. The secondary analysis of RV1 suggested a potential risk, although the study of RV1 was underpowered. These risks must be considered in light of the demonstrated benefits of rotavirus vaccination. (Funded by the Food and Drug Administration.) 

15. Treatment of Calcium Channel Blocker Poisoning: Should We Reprioritize Our Potpourri of Treatment Options?

Pfeffer AN, et al. Ann Emerg Med. 2014;63:259-265.  

16. Traumatic lacerations: what are the risks for infection and has the ‘golden period’ of laceration care disappeared?

Quinn JV, et al. Emerg Med J  2014;31:96-100    

Objective To determine risk factors associated with infection and traumatic lacerations and to see if a relationship exists between infection and time to wound closure after injury.  

Methods Consecutive patients presenting with traumatic lacerations at three diverse emergency departments were prospectively enrolled and 27 variables were collected at the time of treatment. Patients were followed for 30 days to determine the development of a wound infection and desire for scar revision.  

Results 2663 patients completed follow-up and 69 (2.6%, 95% CI 2.0% to 3.3%) developed infection. Infected wounds were more likely to receive a worse cosmetic rating and more likely to be considered for scar revision (RR 2.6, 95% CI 1.7 to 3.9). People with diabetes (RR 2.70, 95% CI 1.1 to 6.5), lower extremity lacerations (RR 4.1, 95% CI 2.5 to 6.8), contaminated lacerations (RR 2.0, 95% CI 1.2  to 3.4) and lacerations greater than 5 cm (RR 2.9, 95% CI 1.6 to 5.2) were more likely to develop an infection. There were no differences in the infection rates for lacerations closed before 3% (95% CI 2.3% to 3.8%) or after 1.2% (95% CI 0.03% to 6.4%) 12 h. 

Conclusions Diabetes, wound contamination, length greater than 5 cm and location on the lower extremity are important risk factors for wound infection. Time from injury to wound closure is not as important as previously thought. Improvements in irrigation and decontamination over the past 30 years may have led to this change in outcome. 

17. Ultrasound: Undifferentiated Hypotension

Marcucci J, et al, Emergency Physicians Monthly, January 15, 2014 

An 84-year-old woman is brought to the emergency department by ambulance for evaluation of altered mental status and syncope. Per family, the patient had complaints of abdominal pain for two days, tactile fevers, decreased PO intake and one episode of non-bloody, non-bilious vomiting. The patient also fell from her bed to the carpet with loss of consciousness for 10 seconds. Her review of systems is negative for: focal weakness, aphasia, seizures, chest pain, shortness of breath, cough, jaundice, icterus, change in stool color, dysuria, hematuria, urinary odor, diarrhea, hematemesis, hematochezia and melena. 

At baseline, the patient lives with her son, but is independent in all activities of daily living, and has no physical or mental deficits.  Her past medical history is significant for hypertension and hyperlipidemia, and her only medication is hydrochlorothiazide daily. 

Her physical exam reveals an elderly female in no acute respiratory distress. Vital signs are significant for tachycardia to 130 bpm and a low grade fever to 38.3C. Initial blood pressure was normotensive at 114/90 mmHg. Abdominal exam was notable for mild periumbilical tenderness. There were no significant neurological deficits and the patient was alert and oriented x 2. She was noted to have waxing and waning confusion during her ED evaluation. The remainder of the physical exam was unremarkable. 

A stat head CT and cervical spine CT without contrast revealed no acute intracranial hemorrhage or relevant findings. Upon returning to the emergency department, the patient was noted to be hypotensive with a blood pressure of 80/40 mmHg which responded to a 1L normal saline bolus. Initial I-STAT laboratory studies demonstrated an elevated Troponin I (0.93), a leukocytosis with a left shift (15.7 with 95% neutrophils) and an EKG with sinus tachycardia and no other acute abnormalities.  

Given the patient’s hemodynamic instability and altered mental status, an emergency bedside ultrasound was performed. Her cardiac exam showed a hyperdynamic left ventricle without wall motion abnormalities or pericardial effusion. The IVC was collapsible. There was no abdominal aortic aneurysm or abdominal/pelvic free fluid. These findings were consistent with a high output, low volume state, which with no evidence of bleeding, was consistent with distributive shock. Given her abdominal tenderness on exam, a RUQ ultrasound was performed to evaluate the hepatobiliary system. This showed a dilated common bile duct with several prominent stones (Figures 1 and 2). 

18. Acute Appendicitis: Investigating an Optimal Outer Appendiceal Diameter Cut-Point in a Pediatric Population

Prendergast PM, et al. J Emerg Med. 2014;46:157-164.  

Acute appendicitis is the most common cause of abdominal pain in children requiring operative intervention. Among a number of sonographic criteria to aid in the diagnosis of appendicitis, an outer diameter above 6 mm is the most objective and widely accepted. However, there is a lack of evidence-based standards governing this consensus. 

Study Objectives
The aim of this study was to determine the outer appendiceal diameter that maximizes sensitivity and specificity in a pediatric population. 

A retrospective review of all urgent diagnostic ultrasounds (US) was performed over 2 years in children aged less than 18 years. The diagnostic accuracy of various cut-points was assessed by calculating the sensitivity and specificity and plotting a receiver operating characteristic (ROC) curve. 

The study sample consisted of 398 patients in whom the appendix was visualized on US. The median outer appendiceal diameter was significantly higher in the surgical group compared to the nonsurgical group (9.4 mm; range = 8.1–12.0 vs. 5.5 mm; range = 4.4–6.5, p less than 0.01). The optimal cut-point with the greatest area under the ROC curve was determined to be an outer appendiceal diameter of 7.0 mm. 

In our patients, adopting a 7-mm rather than a 6-mm appendiceal diameter threshold would balance a greater number of missed cases of acute appendicitis for a reduction in the number of unnecessary surgeries.

19. URIs, Antibiotics Affect Warfarin   

Having an acute upper respiratory tract infection -- with or without treatment with an antibiotic -- may be associated with excessive anti-coagulation in patients taking warfarin, a retrospective study showed. 

Clark NP, et al. JAMA Intern Med. Published online January 20, 2014.  

Importance  The effect of antibiotic coadministration on the international normalized ratio (INR) in a relatively stable, real-world warfarin population has not been adequately described. Case reports and studies of healthy volunteers do not account for the potential contribution of acute illness to INR variability. 

Objective  To compare the risk of excessive anticoagulation among patients with stable warfarin therapy purchasing an antibiotic (antibiotic group) with the risk in patients purchasing a warfarin refill (stable controls) and patients with upper respiratory tract infection but not receiving an antibiotic (sick controls). 

Design, Setting, and Participants  A retrospective, longitudinal cohort study evaluated patients receiving warfarin between January 1, 2005, and March 31, 2011, at Kaiser Permanente Colorado, an integrated health care delivery system. Continuous data were expressed as mean (SD) or median (interquartile range). Multivariable logistic regression analysis was used to identify factors independently associated with a follow-up INR of 5.0 or more. A total of 5857 (48.8%), 5579 (46.5%), and 570 (4.7%) patients were included in the antibiotic, stable control, and sick control groups, respectively. Mean age was 68.3 years, and atrial fibrillation was the most common (44.4%) indication for anticoagulation. 

Exposures  Warfarin therapy with a medical visit for upper respiratory tract infection or coadministration of antibiotics. 

Main Outcomes and Measures  Primary outcomes were the proportion of patients experiencing a follow-up INR of 5.0 or more and change between the last INR measured before the index date and the follow-up INR. 

Results  The proportion of patients experiencing an INR of 5.0 or more was 3.2%, 2.6%, and 1.2% for the antibiotic, sick, and stable groups, respectively (P  less than  .001, antibiotic vs stable control group; P  less than  .017, sick vs stable control group; P = .44, antibiotic vs sick control group). Cancer diagnosis, elevated baseline INR, and female sex predicted a follow-up INR of 5.0 or more. Among antibiotics, those interfering with warfarin metabolism posed the greatest risk for an INR of 5.0 or more. 

Conclusions and Relevance  Acute upper respiratory tract infection increases the risk of excessive anticoagulation independent of antibiotic use. Antibiotics also increase the risk; however, most patients with previously stable warfarin therapy will not experience clinically relevant increases in INR following antibiotic exposure or acute upper respiratory tract infection.

20. What an ED Report Card Tells Us 

By Elbert Chu, Associate Producer, MedPage Today, Jan 16, 2014 

The press release promised that a new report would answer the question: "Are your state's emergency rooms making the grade?" 

But while an American College of Emergency Physicians (ACEP) report card out today said the nation's emergency care environment has worsened since their effort in 2009, it doesn't really answer that specific question. 

ACEP analyzed the condition of emergency care based on state and national policies, which they captured through 136 metrics. These include measures such as numbers of trauma centers and emergency physicians. More relevant for physicians, the 2014 report card includes medical liability measures like average premium levels and average malpractice award payments. Authors divided the indicators into five areas: access, liability, quality and patient safety environment, public health, and disaster preparedness. 

The authors downgraded the U.S. emergency care environment from a "C-" in 2009 to a "D+" this year. The District of Columbia, Massachusetts, and Maine topped the list, while New Mexico, Arkansas, and Wyoming rounded out the bottom. 

But since the grades are based on indicators such as percent of obese children, bicyclist fatalities, and percentage of adults with Medicaid, it's unclear how they would help judge a given state's emergency departments, let alone a specific one. 

It's also unclear how any of these indicators measure what really counts: Patient outcomes. 

What's really unfortunate is that already other media outlets have picked up the report and tied them to emergency departments' quality with headlines like: "N.J. Emergency Rooms get D+ on National Report Card." (That headline seems to have been changed to "N.J.'s Emergency Room Policies get D+ on National Report Card.")

Still, the report card could be helpful on the state and policy level. On a conference call about the report, ACEP president Alex Rosenau, MD, DO, said that some states had responded to the 2009 report with new policies to improve emergency care. 

Jon Mark Hirshon, MD, MPH, PhD, associate professor of emergency medicine at the University of Maryland School of Medicine, who headed the ACEP report task force, said that they'd seen evidence that doctors have migrated to states depending on the liability environment. 

21. Two Good Reads on How our Brains Work 

Matthew D. Lieberman, Social: Why Our Brains Are Wired to Connect (New York: Crown, 2013).  

Bruce Hood, The Self Illusion: How the Social Brain Creates Identity (Oxford: Oxford University Press, 2013). 

22. Tid Bits 

A. Surrogates often make decisions for older patients, study finds  

Indiana University researchers who studied 1,083 hospital patients over age 65 found 570 made all of their own medical decisions, 264 got help from a surrogate and 249 had all of their medical decisions made by someone else. The study in JAMA Internal Medicine found that in the first two days of hospitalization, surrogates made about 60% of decisions regarding life-sustaining treatments and about half of decisions about surgery or discharge destinations. Only about 25% of patients had a living will or advance directive. 

B. Uninsured rate in U.S. is down to 16.1%  

The percentage of Americans without health insurance fell to 16.1% in January, 1.2 percentage points lower than in December, according to a Gallup-Healthways poll. The uninsured rate for unemployed people dropped 6.7 percentage points, the rate for nonwhites fell 2.6 percentage points and the rate for women was down 1.9 points. There was no substantial change in the 18- to 34-year-old demographic. 

C. Topol interviews Gawande 

Atul Gawande, MD, MPH, wears many hats, including that of a surgeon, researcher, journalist, and author. In this segment of Medscape One-on-One, Dr. Gawande talks with Eric J. Topol, MD, about what inspires him, his plans for the future, and why he's secretly a frustrated rock singer. 

D. FDA review finds naproxen safer for heart than other NSAIDs  

FDA reviewers said study data appear to show naproxen does not carry the cardiovascular risks that other nonsteroidal anti-inflammatory drugs do, and the FDA may consider revising the label warning for the drug. All NSAID drugs got boxed warnings in 2005 indicating cardiovascular risks 

Reference Lancet meta-analysis from 2013 (full-text free):   

E. Is communication a casualty of computers in the exam room?  

Research published in the journal Medical Informatics found physicians spend about a third of their time with patients looking at the computer screen, potentially missing nonverbal cues and other subtle forms of communication. "It's likely that the ability to listen, problem-solve and think creatively is not optimal when physicians' eyes are glued to the screen," said researcher Enid Montague. In addition, patients tend to look at the computer screens, although they may not understand the content. 

F. Help patients use OTC medications safely
Each year, thousands of children younger than age 12 end up in emergency rooms as a result of misuse of over-the-counter medications. Help educate your patients about safe, effective use of OTC cold and cough medications. has developed patient education handouts available for free download. 

G. Study: Posters help reduce inappropriate antibiotic scripts  

A RAND Corp. study found that when primary care clinics displayed poster-size letters of clinician commitment to appropriately use antibiotics, it led to reductions in inappropriate prescriptions for the drugs for acute respiratory infections. The report in JAMA Internal Medicine found prescribing rates increased slightly among clinicians in the study who were assigned to follow standard prescribing practices. 

H. Spouse's diabetes tied to increased risk of developing the condition  

People whose spouses had type 2 diabetes had 26% increased odds of developing the disease, according to an analysis in BMC Medicine. "The results of our review suggest that diabetes diagnosis in one spouse may warrant increased surveillance in the other," said senior author Dr. Kaberi Dasgupta.

Full-text (free): 

I. Early vs. Delayed Cholecystectomy for Acute Cholecystitis   

Early surgery is the better choice for patients who aren't critically ill. 

J. Fewer Kids Dying in Car Accidents  

Motor vehicle crashes are a leading cause of death for children in the US. Buckling up is the best way to save lives and reduce injuries. 

Child passenger restraint laws result in more children being buckled up. Only 2 out of every 100 children live in states that require car seat or booster seat use for children age 8 and under. 

A third of children who died in crashes in 2011 were not buckled up. We—especially parents and caregivers—can do more to protect children on the road. 

K. Insulin Pill Passes Safety Test   

A pill formulation of insulin has met safety and pharmacokinetic endpoints in a phase IIa trial, developer Oramed announced.