Wednesday, January 15, 2014

Lit Bits: Jan 15, 2014

From the recent medical literature... 

1. 2013 in Review: Medical and Cultural  

A. Journal Watch: Emergency Medicine Editors' Choice: Top Stories of 2013 

Ron M. Walls, MD, FRCPC, FAAEM. 

A perspective on the most important research in the field from the past year 

As in past years, we have selected for you the studies we feel most important to your practice, summarized these, and provided insightful and directive comments to help you put the knowledge into a clinical perspective. As we do each year, this month we feature the 10 summaries from 2013 that we feel are most important for you to be aware of, to think about, and to discuss with others. You may want to navigate back to the original studies, or simply to review these summaries again to refresh your memory.  

The year brought new clarity to compression-only CPR, rapid blood pressure control during acute intracranial hemorrhage, and the endlessly distracting etomidate in sepsis argument. Iconoclastic studies challenged the Wells and modified Geneva scores for acute pulmonary embolism, and the Alvarado score for appendicitis. And, of course, there was more.
  • Is Intensive Blood Pressure Lowering Beneficial in Acute Intracerebral Hemorrhage?
    • Equivocal outcomes from the INTERACT 2 trial
  • More Information on Thrombolysis Benefits for Ischemic Stroke
    • Two studies using large databases provide details on timing and outcomes
  • Steroid-Pressor Cocktail for In-Hospital Cardiac Arrest?
    • This combination improved neurologically favorable survival
  • Etomidate Does Not Increase Mortality in Intubated Septic Patients
    • In large cohort of intensive care unit patients with sepsis, use of etomidate as the induction agent was not associated with increased mortality or other adverse outcomes
  • Meta-Analysis Finds Ultrasound Guidance Superior to Landmark Technique for Central Venous Catheter Placement
    • In adults, use of the ultrasound approach lowered the risk for cannulation failure and adverse events
  • CPR: Compression-Only Wins the Long Race
    • No full-access review available
  • Acetylcysteine for Prevention of Contrast-Induced Nephropathy
    • Hydration with normal saline alone may be the best approach for most patients
  • Pretest Probability for PE: Structured Scoring System or Clinical Judgment?
    • Your gut feeling is probably as accurate as a structured score like the Wells score for pulmonary embolism
  • Poor Performance of an Appendicitis Decision Rule
    • In this prospective study, the modified Alvarado score had a sensitivity of only 72%
  • Volume of Crystalloid During Massive Transfusion Is Associated with Increased Mortality
    • Minimize use of crystalloid during resuscitation in trauma patients

B. If you could put 10 things from 2013 in the Smithsonian, what would they be?  

By: Katelyn Polantz. PBS Newshour  

NASA's Curiosity took this "selfie" on Mars in February. If he had his way, the Smithsonian's undersecretary for history, art and culture Richard Kurin would have a spot for the rover at the museum.  

When Richard Kurin's hefty book "The Smithsonian's History of America in 101 objects" landed on my desk this year, it made me wonder: What artifacts from 2013 would we want to keep as tangible fragments of history? My first thought was that this year may have less important -- for lack of a better word -- "stuff" than in the past. Hadn't we moved our culture to a place where our apps and tweets were more important than items people made by hand? Not just yet says Kurin, an undersecretary at the Smithsonian Institute. And so he used his knowledge from overseeing history and art collections at the museum to prove me wrong and come up with this list of items he would collect from 2013. 


C. 2013 in Illustrations and Video Clips 



2. Should All Patients with COPD Exacerbations Be Treated with Antibiotics?  

Patricia Anne Kritek, MD, EdM. Journal Watch Emerg Med, December 26, 2013 

In those with mild-to-moderate chronic obstructive pulmonary disease, only purulent sputum and high C-reactive protein levels predicted need for antibiotics.  

Patients with severe chronic obstructive pulmonary disease (COPD) exacerbations are treated with antibiotics, but do patients with less-severe disease also need them? In a 2012 trial of outpatients with mild-to-moderate COPD exacerbations (forced expiratory volume in 1 second, over 50% of predicted) who received either amoxicillin/clavulanate or placebo, 80% of 152 placebo patients had satisfactory outcomes in the absence of antibiotic therapy (Am J Respir Crit Care Med 2012; 186:716). 

To predict which patients would do well without antibiotics, investigators examined the data from the placebo group of this trial. COPD exacerbations were defined by the classical symptoms of increased dyspnea, increased volume of sputum, and increased purulence of sputum. Using multivariate analyses, the researchers determined which factors were associated with potential response to antibiotics. The only symptom that predicted potential benefit from antibiotics was increased purulence of sputum; patients with dyspnea, increased sputum volume (but not increasing purulence), or both did well without receiving antibiotics. The two best predictors of potential benefit from antibiotics were purulent sputum and C-reactive protein (CRP) level over 40 mg/L.  

Comment: This study's finding about use of point-of-care C-reactive protein testing will have limited clinical relevance in settings where such testing is not available. However, this study does support forgoing antibiotics in patients who have mild-to-moderate COPD exacerbations without purulent sputum.  

Miravitlles M et al. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 2013 Nov; 144:1571. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/23807094  

3. Possible Appendicitis? Study Supports Diagnostic Ultrasound 

Linda Roach, Medscape Medical News. December 30, 2013 

Emergency departments can improve their diagnostic accuracy and expose fewer children to unnecessary radiation by adding selective ultrasonography to their diagnostic protocol for suspected appendicitis, according to a study published online December 30 in Pediatrics. 

Ashley Saucier, MD, from the Division of Emergency Services, Department of Pediatrics, University of Tennessee Health Science Center, and Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Memphis, Tennessee, and colleagues evaluated outcomes in 196 patients (aged 3 - 17 years) who presented at the University of Tennessee Health Sciences Center with abdominal pain. Under the study protocol, physicians assessed the patient's risk for appendicitis using a pediatric appendicitis score (PAS), which is a validated system commonly used in emergency departments. However, this 10-point scale of signs, symptoms, and findings from laboratory tests has been shown to have insufficient sensitivity and specificity to diagnose appendicitis by itself. 

If the child had a PAS of 4 to 7 or was at intermediate risk, abdominal ultrasound imaging was performed at the treating physician's discretion. However, computed tomography (CT) scans were not part of the clinical pathway for such children. Children with high-risk PAS scores (≥8) were referred to a pediatric surgeon for management, and CT was performed only at the request of the surgeon.

This clinical pathway resulted in ultrasonography in 128 (65.3%) patients, and 48 (37.5%) of these exams were positive for appendicitis. CT scans were requested by the surgical consultants in 13 (6.6%) cases. Of the 65 patients diagnosed with appendicitis, none had a low-risk PAS score, 37 (56.9%; 95% confidence interval [CI], 44.4% - 69.2%) had an intermediate score and 28 (43.1%; 95% CI, 30.9% - 56.0%) had a high-risk score.

Further analysis found that the pathway had diagnostic accuracy of 94% (95% CI, 91% - 97%), with a sensitivity of 92.3% (95% CI, 83.0% - 97.5%), specificity of 94.7% (95% CI, 89.3% - 97.8%), positive likelihood ratio of 17.3 (95% CI, 8.4 - 35.6), and negative likelihood ratio of 0.08 (95% CI, 0.04 - 0.19).

"Our results demonstrate that the diagnostic accuracy of our clinical pathway to risk-stratify patients with suspected appendicitis was superior to using the PAS alone, with significantly improved sensitivity and specificity," the researchers note. 

This is important because it suggests that a PAS score combined with ultrasound could in most cases spare children with suspected appendicitis from undergoing CT, the researchers wrote. During the last decade, pediatricians have expressed alarm about the increasing use of CT for diagnosis in children because this exposes them to potential harm from the ionizing radiation. 

Saucier A, et al. Pediatrics. 2014 Jan;133(1):e88-95. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/24379237  

4. Topical Lidocaine Failed to Improve Oral Intake in Children with Painful Infectious Mouth Ulcers: A Blinded, Randomized, Placebo-Controlled Trial


Hopper SM, et al. Ann Emerg Med. 2013 Nov 7  [Epub ahead of print] 

Study objective: We establish the efficacy of 2% viscous lidocaine in increasing oral intake in children with painful infectious mouth conditions compared with placebo. 

Methods: This was a randomized placebo-controlled trial of viscous lidocaine versus placebo at a single pediatric emergency department. Study staff, clinicians, nurses, caregivers, and participants were blinded to the group assignment. Children with acute infectious ulcerative mouth conditions (gingivostomatitis, ulcerative pharyngitis, or hand, foot, and mouth disease) and poor oral fluid intake were randomized to receive 0.15 mL/kg of either 2% viscous lidocaine or placebo with identical appearance and flavor. The primary outcome was the amount of fluid ingested in the 60 minutes after administration of the intervention, with a difference in intake of 4 mL/kg considered clinically important. Secondary outcomes were specific milliliter per kilogram fluid targets and incidence of adverse events. 

Results: One hundred participants were recruited (50 per treatment group), all of whom completed the 60-minute fluid trial period. Oral intake 1 hour after drug administration was similar in both groups: lidocaine median 8.49 mL/kg (interquartile range 4.07, 13.84 mL/kg) versus placebo 9.31 mL/kg (interquartile range 3.06, 15.18 mL/kg); difference in medians 0.82 mL/kg (95% confidence interval –2.52 to 3.26); Mann-Whitney P=.90. Likewise, short-term secondary outcomes were similar between the groups and there were no adverse events in either group. 

Conclusion: Viscous lidocaine is not superior to a flavored gel placebo in improving oral intake in children with painful infectious mouth ulcers. 

5. CVC Placement Evaluation Using Saline Flush and Bedside Echo

Weekes AJ, et al. Acad Emerg Med. 2014;21:65-72.  

Objectives: Central venous catheter (CVC) placement is a common procedure in critical care management. The authors set out to determine echocardiographic features during a saline flush of any type of CVC. The hypothesis was that the presence of a rapid saline swirl in the right atrium on bedside echocardiography would confirm correct placement of the CVC tip, similar to the accuracy of the postplacement chest radiograph (CXR). 

Methods: This was a prospective convenience sample of emergency department (ED) and intensive care unit (ICU) patients who had CVCs placed. Investigators used subcostal or apical four-chamber echocardiography windows to evaluate the onset and appearance of turbulent flow in the right atrium when the distal port of the CVC was flushed with 10 mL of saline. Onset was rated as “immediate” (within 2 seconds), “delayed” (2 to 6 seconds), or “absent” (did not appear within 6 seconds). Appearance was rated as “prominent,” “speckling,” or “absent.” Digital video review was used later to objectively determine precise timing of turbulence onset. The rapid atrial swirl sign (RASS) was defined as the echo appearance of turbulence entering the right atrium immediately (within 2 seconds) after the saline flush of the CVC distal port. The observance of RASS (“positive”) was considered “negative” for CVC malposition. Echocardiographic results were compared to CVC tip locations within predetermined zones on the CXR. Superior vena cava (SVC) region was considered the optimal CVC tip position for subclavian and internal jugular CVC. Left CVC tips within the mid left innominate vein were also considered appropriately placed. 

Results: A total of 142 patients enrolled, yielding 152 CVCs. Two CVCs were excluded from analysis due to incomplete data. Both CXR and echocardiographic images for 107 internal jugular CVCs and 28 subclavian CVCs were available for analysis. Saline flush echo evaluations were also performed on 15 femoral CVCs. Either 16-cm triple-lumen or 20-cm PreSep CVCs were used. CVC malposition was discovered on CXR in four of 135 (3.0%) of the subclavian and internal jugular CVCs. RASS for subclavian and internal jugular CVC evaluations versus CXR results for CVC tip malposition yielded 75% sensitivity, 100% specificity, positive predictive value (PPV) 100% (95% confidence interval [CI] = 29.24% to 100%), and negative predictive value (NPV) 99.24% (95% CI = 95.85% to 99.98%). Mean (±SD) time for onset of saline flush turbulence was 1.1 (±0.3) seconds for subclavian and internal jugular CVC tips within the target CXR zone. 

Conclusions: The rapid appearance of prominent turbulence in the right atrium on echocardiography after CVC saline flush serves as a precise bedside screening test of optimal CVC tip position. 

6. Red flags to screen for malignancy and fracture in patients with low back pain: systematic review


Downie A, et al. BMJ 2013;347:f7095  

Objective To review the evidence on diagnostic accuracy of red flag signs and symptoms to screen for fracture or malignancy in patients presenting with low back pain to primary, secondary, or tertiary care. 

Design Systematic review. 

Data sources Medline, OldMedline, Embase, and CINAHL from earliest available up to 1 October 2013. 

Inclusion criteria Primary diagnostic studies comparing red flags for fracture or malignancy to an acceptable reference standard, published in any language. 

Review methods Assessment of study quality and extraction of data was conducted by three independent assessors. Diagnostic accuracy statistics and post-test probabilities were generated for each red flag. 

Results We included 14 studies (eight from primary care, two from secondary care, four from tertiary care) evaluating 53 red flags; only five studies evaluated combinations of red flags. Pooling of data was not possible because of index test heterogeneity. Many red flags in current guidelines provide virtually no change in probability of fracture or malignancy or have untested diagnostic accuracy. The red flags with the highest post-test probability for detection of fracture were older age (9%, 95% confidence interval 3% to 25%), prolonged use of corticosteroid drugs (33%, 10% to 67%), severe trauma (11%, 8% to 16%), and presence of a contusion or abrasion (62%, 49% to 74%). Probability of spinal fracture was higher when multiple red flags were present (90%, 34% to 99%). The red flag with the highest post-test probability for detection of spinal malignancy was history of malignancy (33%, 22% to 46%). 

Conclusions While several red flags are endorsed in guidelines to screen for fracture or malignancy, only a small subset of these have evidence that they are indeed informative. These findings suggest a need for revision of many current guidelines. 

7. Warming IV fluids improves patient comfort in the ED: a pilot crossover RCT 

Self WH, et al. West J Emerg Med. 2013 Sep;14(5):542-6.

Introduction: The purpose of this study was to test if intravenous (IV) fluids warmed to body temperature are associated with greater patient comfort than room temperature IV fluids in adult emergency department (ED) patients. 

Methods: This was a pilot double-blind, crossover, randomized controlled trial. Enrolled subjects sequentially received boluses of body temperature (36ºC) and room temperature (22 ºC) IV fluid, with the order of boluses randomized. Each subject’s level of discomfort was assessed prior to and after each bolus, using a 10 cm visual analog scale (Discomfort VAS), with higher scores indicating greater discomfort. We calculated the change in Discomfort VAS score associated with body temperature IV fluid (ΔVASbody) and room temperature IV fluid (ΔVASroom) by subtracting the score reported before the bolus from the score reported after that bolus. We compared changes in Discomfort VAS score with body temperature and room temperature IV fluid using the Wilcoxon matched-pairs signed-rank test. 

Results: Twenty-seven subjects were included. Treatment with body temperature IV fluid was associated with a significant decrease in discomfort (median ΔVASbody: -0.7 cm; interquartile range (IQR): -4.5 cm to +0.4 cm) compared to room temperature IV fluid (median ΔVASroom: +1.2 cm; interquartile range: -0.1 cm to + 3.6 cm) (P = 0.001). 

Conclusion: In this small trial of adult ED patients, infusing IV fluids warmed to body temperature was associated with improved comfort compared to standard, room temperature IV fluids.  


8. High BMI Obviates the Need for Oral Contrast for Abdominal-Pelvic CT in ED Patients 

Harrison ML, et al. West J Emerg Med.2013;14(6):595–597. 

Introduction: High body mass index (BMI) values generally correlate with a large proportion of intra-peritoneal adipose tissue. Because intra-peritoneal infectious and inflammatory conditions manifest with abnormalities of the adipose tissue adjacent to the inflamed organ, it is presumed that with a larger percentage of adipose surrounding a given organ, visualization of the inflammatory changes would be more readily apparent. Do higher BMI values sufficiently enhance the ability of a radiologist to read a computed tomography of the abdomen and pelvis, so that the need for oral contrast to be given is precluded? 

Methods: Forty six patients were included in the study: twenty seven females, and nineteen males. They underwent abdominal/pelvic CTs without oral or intravenous contrast in the emergency department. Two board certified radiologists reviewed their CTs, and assessed them for radiographic evidence of intra-abdominal pathology. The patients were then placed into one of four groups based on their body mass index. Kappa analysis was performed on the CT reads for each group to determine whether there was significant inter-rater agreement regarding contrast use for the patient in question. 

Results: There was increasingly significant agreement between radiologists, regarding contrast use, as the study subject’s BMI increased. In addition, there was an advancing tendency of the radiologists to state that there was no need for oral or intravenous contrast in patients with higher body mass indices, as the larger quantity of intra-peritoneal adipose allowed greater visualization and inspection of intra-abdominal organs. 

Conclusion: Based on the results of this study, it appears that there is a decreasing need for oral contrast in emergency department patients undergoing abdominal/pelvic CT, as a patient’s BMI increases. Specifically, there was statistically significant agreement, between radiologists, regarding contrast use in patients who had a BMI greater than twenty-five.  


9. Study Supports Cognitive Rest Following Concussion [and ED shifts?] 

Pauline Anderson. Medscape Medical News. January 08, 2014. 

Following a concussion, young athletes engaging the most in activities requiring concentration and attention (eg, doing homework, text messaging, and playing video games) take the longest time to recover, a new study has found. 

The study results are in line with current recommendations for limiting extensive cognitive activity after a head injury. 

But while the study findings support the use of cognitive rest, they don't suggest being completely idle following a concussion. 

"The study actually found that athletes doing mild and moderate levels of cognitive activity recovered from a concussion at about the same rate as those doing minimal amounts of activity," lead author William P. Meehan III, MD, director, Micheli Center for Sports Injury Prevention, and director, Sports Concussion Clinic, Children's Hospital, Boston, Massachusetts, told Medscape Medical News. "It's only those doing the highest levels of cognitive activity that tend to draw out their recovery." 

The remainder of the Medscape article: http://www.medscape.com/viewarticle/818840  

10. Images in Clinical Medicine 

An Unknowingly Swallowed Inedible Toy

Acupuncture with Gold Thread for Osteoarthritis of the Knee

A Painful, Blistering Rash

Visualization of Cardiac Thrombus by Bedside Ultrasound

Total Collapse of the Heart

Evolution of a Round Pneumonia

Olivier Syndrome: Traumatic Asphyxia

Digital Frostbite 

Halo Phenomenon 

Left Ventricular Aneurysm

11. Avoidable Antibiotic Exposure for Uncomplicated Skin and Soft Tissue Infections in the Ambulatory Care Setting


Hurley HJ, et al. Amer J Med 2013;126:1099-1106.  

Background
Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotics. A detailed understanding of current prescribing practices is necessary to optimize antibiotic use for these conditions. 

Methods
This was a retrospective cohort study of children and adults treated in the ambulatory care setting for uncomplicated cellulitis, wound infection, or cutaneous abscess between March 1, 2010 and February 28, 2011. We assessed the frequency of avoidable antibiotic exposure, defined as the use of antibiotics with broad gram-negative activity, combination antibiotic therapy, or treatment for 10 or more days. Total antibiotic-days prescribed for the cohort were compared with antibiotic-days in 4 hypothetical short-course (5-7 days), single-antibiotic treatment models consistent with national guidelines. 

Results
A total of 364 cases were included for analysis (155 cellulitis, 41 wound infection, and 168 abscess). Antibiotics active against methicillin-resistant Staphylococcus aureus were prescribed in 61% of cases of cellulitis. Of 139 cases of abscess where drainage was performed, antibiotics were prescribed in 80% for a median of 10 (interquartile range, 7-10) days. Of 292 total cases where complete prescribing data were available, avoidable antibiotic exposure occurred in 46%. This included use of antibiotics with broad gram-negative activity in 4%, combination therapy in 12%, and treatment for 10 or more days in 42%. Use of the short-course, single-antibiotic treatment strategies would have reduced prescribed antibiotic-days by 19% to 55%. 

Conclusions
Approximately half of uncomplicated skin infections involved avoidable antibiotic exposure. Antibiotic use could be reduced through treatment approaches using short courses of a single antibiotic. 


12. Sedative dosing of propofol for treatment of migraine HA in the ED: A case series 

Mosler J, et al. West J Emerg Med. 2013;14(6):646-649. 

Introduction: Migraine headaches requiring an emergency department visit due to failed outpatient rescue therapy present a significant challenge in terms of length of stay (LOS) and financial costs. Propofol therapy may be effective at pain reduction and reduce that length of stay given its pharmacokinetic properties as a short acting intravenous sedative anesthetic and pharmacodynamics on GABA mediated chloride flux. 

Methods: Case series of 4 patients presenting to an urban academic medical center with migraine headache failing outpatient therapy. Each patient was given a sedation dose (1 mg/kg) of propofol under standard procedural sedation precautions. 

Results: Each of the 4 patients experienced dramatic reductions or complete resolution of headache severity. LOS for 3 of the 4 patients was 50% less than the average LOS for patients with similar chief complaints to our emergency department. 1 patient required further treatment with standard therapy but had a significant reduction in pain and a shorter LOS. There were no episodes of hypotension, hypoxia, or apnea during the sedations. 

Conclusion: In this small case series, sedation dose propofol appears to be effective and safe for the treatment of refractory migraines, and may result in a reduced LOS.  


13. A descriptive analysis of patients with an ED diagnosis of acute pericarditis 

Hooper AJ, et al. Emerg Med J. 2013 Dec;30(12):1003-8. 

AIM: To describe clinical characteristics, assessment and treatment of patients diagnosed in an emergency department (ED) with acute pericarditis. 

METHODS: A medical record review of patients with an ED diagnosis of pericarditis conducted in an adult tertiary hospital over a 5-year period. Variables collected included pain characteristics, associated symptoms, physical examination findings, investigation results, ED treatment and disposition. 

RESULTS: 179 presentations were included, with 73.9% men and a mean age of 38.8 years. The majority of patients described pleuritic chest pain worse with inspiration with half characterising the pain as sharp or stabbing, with others describing tightness, dullness or cramping. Radiation to the left shoulder occurred in 2.8% and change of pain with posture occurred in 46.4%. A pericardial rub was documented in 19 presentations. All patients had an ECG recorded with ST segment elevation present in 69.3% and PR segment depression in 49.2%. Nearly 90% of patients had troponin testing but only 6.4% of these were positive. Only 8.1% of cases were treated with colchicine. No patients required pericardiocentesis. Patients with high-risk factors were more likely to have previous pericarditis, dyspnoea, nausea, abnormal investigation results, treatment with colchicine and admission to hospital. However, 16.9% of patients without risk factors were admitted, and 46.9% of patients with at least one risk factor were discharged. 

CONCLUSIONS: Pericarditis may not follow the classical clinical description. Admission and discharge decisions appear to relate to individual clinical characteristics rather than known risk factors. Use of colchicine for treatment in ED is infrequent. 

14. Medicaid Access Increases Use of EDs by 40%  

Joe Elia, Physician’s First Watch Medical News | Physician's First Watch January 3, 2014 

Increased availability of Medicaid coverage is associated with higher use of emergency departments (EDs), according to a Science article. 

Oregon modestly widened Medicaid access among low-income adults in 2008 through a lottery. The randomized nature of the lottery enabled researchers to compare ED use among lottery winners with use among those who applied but didn't win (controls). 

During an 18-month observation period, ED visits increased by 40% among those covered by Medicaid relative to those without coverage: overall, Medicaid enrollees had an average of 1.43 ED visits, versus 1.02 among controls. Coverage increased ED use for all types of nonemergency visits, including those rated as "primary care treatable." The proportion of visits resulting in hospital admission, however, did not increase. 

A commentator writes that under the Affordable Care Act, "we have good reason to anticipate a large increase — and almost surely not a decrease — in traffic to already overburdened emergency departments across the country."  


15. Low-Dose Dopamine or Low-Dose Nesiritide in Acute HF with Renal Dysfunction: The ROSE Acute HF Randomized Trial


Chen HH, et al. JAMA. 2013;310(23):2533-2543.  

Importance  Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. 

Objective  To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. 

Design, Setting, and Participants  Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. 

Interventions  Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). 

Main Outcomes and Measures  Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). 

Results  Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, −714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, −0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, −618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, −0.04; 95% CI, −0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. 

Conclusion and Relevance  In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. 

16. Safe-Dose Thrombolysis Plus Rivaroxaban for Moderate and Severe Pulmonary Embolism: Drip, Drug, and Discharge.

Shatifi M, et al. Clin Cardiol 2013 Oct 7 [Epub ahead of print]

 BACKGROUND: Thrombolysis, though very effective, has not been embraced as routine therapy for symptomatic pulmonary embolism (PE) except in very severe cases. Rivaroxaban recently has been approved for the treatment of venous thromboembolism (VTE). There are no data on the combined use of thrombolysis and rivaroxaban in PE. 

HYPOTHESIS: "Safe dose" thrombolysis (SDT) plus new oral anticoagulants are expected to become an appealing, safe and effective approach in the treatment of moderate and severe PE in the near future, thereby drastically reducing hospitalization time. 


METHODS: Over a 12-month period, 98 consecutive patients with symptomatic PE were treated by a combination of SDT and rivaroxaban. The SDT was started in parallel with unfractionated heparin and given in 2 hours. Heparin was given for a total of 24 hours and rivaroxaban started at 15 or 20 mg daily 2 hours after termination of heparin infusion. 

RESULTS: There was no bleeding due to SDT. Recurrent VTE occurred in 3 patients who had been switched to warfarin. No patient on rivaroxaban developed VTE. Two patients died of cancer at a mean follow-up of 12 ± 2 months. The pulmonary artery systolic pressure dropped from 52.8 ± 3.9 mm Hg before to 32 ± 4.4 mm Hg within 36 hours of SDT (P less than 0.001). The duration of hospitalization for patients presenting primarily for PE was 1.9 ± 0.2 days. 

CONCLUSIONS: "Safe dose" thrombolysis plus rivaroxaban is highly safe and effective in the treatment of moderate and severe PE, leading to favorable early and intermediate-term outcomes and early discharge. 

DRV Note: Who was included? All patients had ≥3 new signs and symptoms: chest pain, tachypnea (resting respiratory rate ≥22/min), tachycardia (resting heart rate≥90/min), dyspnea, oxygen desaturation (resting PO2 less than 95%), or elevated jugular venous pressure (≥10 cm H2O) 

What was the lytic dose? tPA was given in parallel with heparin and within 2 hours of admission for most patients. In brief, the patients received 50 mg of tPA, which was given as a 10-mg bolus by an intravenous push within 1 minute, followed by infusion of the remaining 40 mg within 2 hours. Described for fully here: Sharifi M, et al; "MOPETT" Investigators. Moderate Pulmonary Embolism Treated With Thrombolysis (from the "MOPETT" Trial) Am J Cardiol. 2013;111:273-277.  



17. Incidence of Clinically Important Biphasic Reactions in ED Patients with Allergic Reactions or Anaphylaxis


Grunau BE, et al. Ann Emerg Med. 2013 Nov 13. [Epub ahead of print]

Study objective: Allergic reactions are common presentations to the emergency department (ED). An unknown proportion of patients will develop biphasic reactions, and patients are often monitored for prolonged periods to manage potential reactions. We seek to determine the incidence of clinically important biphasic reactions. 

Methods: Consecutive adult patients presenting to 2 urban EDs with allergic reactions during a 5-year period were identified. Encounters were dichotomized as “anaphylaxis” or “allergic reaction” with an explicit algorithm. A comprehensive chart review was conducted on each index and all subsequent visits to detail patient presentations, comorbidities, ED management, and predefined clinically important biphasic reactions. Regional and provincial databases were linked to identify subsequent ED visits and deaths within a 7-day period. The primary outcome was the proportion of patients with a clinically important biphasic reaction, and the secondary outcome was mortality.

Results: Of 428,634 ED visits, 2,819 (0.66%) encounters were reviewed (496 anaphylactic and 2,323 allergic reactions). Overall, 185 patients had at least 1 subsequent visit for allergic symptoms. Five clinically important biphasic reactions were identified (0.18%; 95% confidence interval [CI] 0.07% to 0.44%), with 2 occurring during the ED visit and 3 postdischarge. There were no fatalities (95% CI 0% to 0.17%). In the anaphylaxis and allergic reaction groups, clinically important biphasic reactions occurred in 2 patients (0.40%; 95% CI 0.07% to 1.6%) and 3 patients (0.13%; 95% CI 0.03% to 0.41%), respectively. 

Conclusion: Among ED patients with allergic reactions or anaphylaxis, clinically important biphasic reactions and fatalities are rare. Our data suggest that prolonged routine monitoring of patients whose symptoms have resolved is likely unnecessary for patient safety. 

18. Accuracy of point-of-care multiorgan US for the diagnosis of PE

Nazerian P, et al. Chest. 2013 Oct 3 [Epub ahead of print] 

ABSTRACT BACKGROUND: Presenting signs and symptoms of pulmonary embolism (PE) are non-specific, favoring a large use of second-line diagnostic tests such as multi-detector computed tomography pulmonary angiography (MCTPA), thus exposing patients to high-dose radiation and to potential serious complications. We investigated the diagnostic performance of multiorgan ultrasonography (lung, heart and leg veins ultrasonography) and if multiorgan ultrasonography combined to Wells score and D-dimer could safely reduce MCTPA tests.

METHODS: Consecutive adult patients suspected of PE and with a Wells score >4 or a positive D-dimer were prospectively enrolled in three emergency departments. Final diagnosis was obtained with MCTPA. Multiorgan ultrasonography was performed before MCTPA and considered diagnostic for PE if one or more subpleural infarcts, right ventricular dilatation or deep vein thrombosis were detected. If multiorgan ultrasonography was negative for PE, an alternative ultrasonography diagnosis was searched for. Accuracies of each single-organ and multiorgan ultrasonography were calculated. 

RESULTS: PE was diagnosed in 110 (30.8%) out of 357 enrolled patients. Multiorgan ultrasonography yielded a sensitivity of 90% and a specificity of 86.2%, lung ultrasonography of 60.9% and 95.9%, heart ultrasonography of 32.7% and 90.9% and vein ultrasonography of 52.7% and 97.6% respectively. Among the 132 (37%) patients with multiorgan ultrasonography negative for PE plus an alternative ultrasonographic diagnosis or plus a negative D-dimer, no patients had PE as final diagnosis. 

CONCLUSIONS: Multiorgan ultrasonography is more sensitive than single-organ ultrasonography, increases the accuracy of clinical pre-test probability estimation in patients with suspected PE and may safely reduce the MCTPA burden. 

19. Predictors of unattempted central venous catheterization in septic patients eligible for early goal-directed therapy

Vinson DR, et al, for the Kaiser Permanente CREST Network Investigators. West J Emerg Med. 2014; 2014 Jan 7 [Epub ahead of print]

Introduction: Central venous catheterization (CVC) can be an important component of the management of patients with severe sepsis and septic shock. CVC, however, is a time- and resource-intensive procedure associated with serious complications. The effects of the absence of shock or the presence of relative contraindications on undertaking central line placement in septic emergency department (ED) patients eligible for early goal-directed therapy (EGDT) have not been well described. We sought to determine the association of relative normotension (sustained systolic blood pressure above 90 mmHg independent of or in response to an initial crystalloid resuscitation of 20 mL/kg), obesity (body mass index [BMI] ≥30), moderate thrombocytopenia (platelet count less than 50,000 per μL), and coagulopathy (international normalized ratio ≥2.0) with unattempted CVC in EGDT-eligible patients.  

Methods: This was a retrospective cohort study of 421 adults who met EGDT criteria in 5 community EDs over a period of 13 months. We compared patients with attempted thoracic (internal jugular or subclavian) CVC with those who did not undergo an attempted thoracic line. We also compared patients with any attempted CVC (either thoracic or femoral) with those who did not undergo any attempted central line. We used multivariate logistic regression analysis to calculate adjusted odd ratios (AORs).  

Results: In our study, 364 (86.5%) patients underwent attempted thoracic CVC and 57 (13.5%) did not. Relative normotension was significantly associated with unattempted thoracic CVC (AOR 2.6 95% confidence interval [CI], 1.6-4.3), as were moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.1) and coagulopathy (AOR 2.7; 95% CI, 1.3-5.6). When assessing for attempted catheterization of any central venous site (thoracic or femoral), 382 (90.7%) patients underwent attempted catheterization and 39 (9.3%) patients did not. Relative normotension (AOR 2.3; 95% CI, 1.2-4.5) and moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.3) were significantly associated with unattempted CVC, whereas coagulopathy was not (AOR 0.6; 95% CI, 0.2-1.8). Obesity was not significantly associated with unattempted CVC, either thoracic in location or at any site.  

Conclusion: Septic patients eligible for EGDT with relative normotension and those with moderate thrombocytopenia were less likely to undergo attempted CVC at any site. Those with coagulopathy were also less likely to undergo attempted thoracic central line placement. Knowledge of the decision-making calculus at play for physicians considering central venous catheterization in this population can help inform physician education and performance improvement programs. 


20. Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest: A RCT 

Kim F, et al. JAMA. 2014;311(1):45-52.  

Importance  Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. 

Objective  To determine whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. 

Design, Setting, and Participants  A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4°C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. 

Main Outcomes and Measures  The primary outcomes were survival to hospital discharge and neurological status at discharge. 

Results  The intervention decreased mean core temperature by 1.20°C (95% CI, −1.33°C to −1.07°C) in patients with VF and by 1.30°C (95% CI, −1.40°C to −1.20°C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% [95% CI, 57.0%-68.0%] vs 64.3% [95% CI, 58.6%-69.5%], respectively; P = .69) and among patients without VF (19.2% [95% CI, 15.6%-23.4%] vs 16.3% [95% CI, 12.9%-20.4%], respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% [95% CI, 51.8%-63.1%] of cases had full recovery or mild impairment vs 61.9% [95% CI, 56.2%-67.2%] of controls; P = .69) or those without VF (14.4% [95% CI, 11.3%-18.2%] of cases vs 13.4% [95% CI,10.4%-17.2%] of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% [95% CI, 22%-29%] vs 21% [95% CI, 18%-24%], respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. 

Conclusion and Relevance  Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34°C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. 

21. A (Belated) Letter to Santa: What the Big Guy Really Needs to Hear 

Ballard DM. Dec 21, 2013 

Doctor I.M. Igloo
North Pole Community Health Clinic, North Pole 

Dear Mister Claus, 

I am writing to ask your indulgence with a manifesto of unsolicited advice. Being mindful of the vast amount of correspondence you receive, I nonetheless ask that you pay close attention to this letter, as it is of immense importance. Truth be told, it may be a matter of life or death. 

Mister Claus, you are too fat. That is impolitic, I know, but based on the data from your most recent check-up, you are, without a doubt, morbidly obese. Mr. Claus, have you heard about the BMI? No, this is not new Xbox lingo; it is your body mass index. And yours is unsightly; like a gift wrapped in toilet tissue. Based on your height and weight you have a BMI of 44 – which is far above the normal range of 25 to 30. This, I’m afraid, places you in danger of myriad medical conditions: diabetes, high blood pressure, heart disease, and arthritis, to name a handful. It also amplifies the chimney-related occupational risk you face each December 24th. In sum, this is a great jolly health disaster just waiting to happen. 

Mister Claus, perhaps you saw the 2009 Harvard study published in the New England Journal of Medicine? The authors calculated future life expectancies based on current and historical data and found that the heavy tide of obesity will likely wipe out all of the societal benefits of smoking cessation efforts. I shall quote Susan T. Stewart, Ph.D., lead author on the study; "In the past 15 years, smoking rates have declined by 20 percent, but obesity rates have increased by 48 percent. If past trends continue, nearly half of the population (45 percent) is projected to be obese by 2020." Now, this is a sensitive topic for many people, and I recognize that, genetically speaking, people come in all shapes and sizes. Maintaining a healthy weight is much easier for some than for others. But, nonetheless I fear that you have chosen image over sensibility. 

So, Mister Claus, because I am greatly concerned for your well being (not to mention that of the world’s children), I have put together a holiday wish-list for your health. 

1) Mini-size the portions. I have heard that Mrs. Claus makes a delicious potpie and that your home is filled with candy canes and sugarplums. Temptation is everywhere in your cozy nook of the world. All I would ask is that you keep the portions reasonable and only eat when you are hungry. One more thing, don’t feel obligated to politely consume each tasty morsel left for you above the fireplace – save some for the Grinch, his frame can spare an extra cookie or two. And, for goodness sake, have some broccoli with your potatoes – not only does it help fill you up, but it also contains phytochemicals that may help ward off diabetes, heart disease and obesity.
2) Pay attention to the calories when dining out. Eating well on the road is tough, I don’t have to tell you that. But, you should know that most people grossly underestimate the number of calories in a restaurant meal. Restaurant chains may soon be required to calorie-label their menus. In the meantime, you might consider gifting yourself a copy of Eat This Not That! 2010. This useful tome gives you an idea of the calories in common restaurant meals. For instance, the grilled chicken and avocado club at the Cheesecake Factory brings home over 1700 calories (better split that with the Missus). And, one last thing, when you park the sleigh at the convenience store, just say No-Nos to the Ho-Hos. 

3) Don’t let the reindeer do all the work. Or the elves for that matter. A year’s worth of armchair-based supervision followed by a night of sitting in a sleigh is appallingly sedentary. Like many people, I am sure that you find it difficult to carve out dedicated time for exercise. So, why not make exertion part of your work? You may have seen the recent evidence that suggests that men who walk or bike to work enjoy better health than those who do not (even when controlling for other types of physical activity). I recommend that you outfit your sleigh with a bicycle apparatus – that way you can give Prancer and Dasher and the boys a little assistance, while servicing your waistline at the same time.

4) Every now and again, consider your own happiness. You may laugh for the children and smile for the camera, but I suspect that your mental health is not as robust as you would have us believe. Research has shown a link between obesity and depression, although it is hard to know which leads to the other. But, whatever the causal link, I am confident that you will find greater contentment with lesser corpulence. 

Mister Claus, thanks for your tolerance with my badgering counsel. Your time is valuable, that I know, but so is your continued good health. Indulge less, live better. 

 Sincerely, 

Dr. I.M. Igloo 


22. Tid Bits 

A. "Compassion fatigue" common among physicians, report finds  

Many respondents to Medscape's 2013 Physician Lifestyle Report survey of U.S. physicians reported feeling "compassion fatigue." While the condition is not new, the fiscal, social, cultural and scientific challenges doctors currently face "have left us unable to provide the support necessary to avoid physician burnout, compassion fatigue, demoralization, and leaving the field," said Richard Levin, M.D., professor emeritus at New York and McGill universities. Being aware of the problem is the first step toward addressing it, which involves focusing more on self-care. 


B. Partial Meniscectomy No Better than Sham for Meniscal Tear 

In this trial of arthroscopic partial meniscectomy in patients with symptoms of a degenerative medial meniscus tear and no knee osteoarthritis, the outcomes after partial meniscectomy were no better than those after sham surgery. 


C. Your Microbiome and You: What Clinicians Need to Know  

Scott Peterson, PhD. December 20, 2013 


D. Poverty May Slow Early Brain Growth 

Megan Brooks. Medscape Medical News. December 19, 2013 

Poverty has a negative impact on the rate of brain growth in children, new research suggests. 

A longitudinal imaging study conducted by investigators at the University of Wisconsin-Madison and the University of North Carolina-Chapel Hill found that by age 4 years, children living in households with income below 200% of the federal poverty line (FPL) had less gray matter ― critical for processing information and executive function ― than their peers from more affluent homes. 

"This is an important link between poverty and biology. We're watching how poverty gets under the skin," study investigator Barbara Wolfe, PhD, said in a statement. 

The researchers also found that smaller gray matter volume correlated with greater behavioral problems in the preschool years. 

"One of the things that is important here is that the infants' brains look very similar at birth. You start seeing the separation in brain growth between the children living in poverty and the more affluent children increase over time, which really implicates the postnatal environment," study coauthor Seth Pollak, PhD, added. 


E. New Drugs and Devices from 2011 – 2012 That Might Change Your Practice 

Joe Lex. West J Emerg Med. 2013;14(6):619-628. 

To be honest, I thought this would be a lost cause.  Even after skipping a New Drugs and Devices essay in 2012, I figured that I would have to search long and hard to find ten new things that emergency practitioners needed to know about.  Although there were no true blockbuster medications for emergency physicians, I nonetheless found ten medicines that we probably should know, along with a new device that may change the way we work up patients with palpitations, and a clever new delivery system for subcutaneous epinephrine. 


F. Hospital-Acquired C. diff Risk Still Highest for Cephalosporins, Clindamycin 

NEW YORK (Reuters Health) Dec 27 - The risk of hospital-acquired Clostridium difficile infection (HA-CDI) is greatest for cephalosporins and clindamycin, researchers from Australia have found. 

Their study, online December 8 in the Journal of Antimicrobial Chemotherapy, updates a systematic review with data up to 2001 that came to a similar conclusion. 

The increasing rates of CDI in industrialized countries and the emergence of the NAP1/RT027 strain in North America and Europe prompted Dr. Claudia Slimings and Dr. Thomas V. Riley from The University of Western Australia in Crowley to reevaluate the associations between antibiotic classes and the risk of HA-CDI from January 2002 to December 2012. 

Their review included 14 studies (13 case-control studies and 1 cohort study) covering nearly 16,000 patients. Overall, antibiotic exposure was associated with a 60% increased risk of CDI. The strongest associations were seen for third-generation cephalosporins (odds ratio, 3.20), clindamycin (OR, 2.86), second-generation cephalosporins (OR, 2.23), fourth-generation cephalosporins (OR, 2.14), carbapenems (OR, 1.84), trimethoprim/sulphonamides (OR, 1.78), fluoroquinolones (OR, 1.66) and penicillin combinations (OR, 1.45). 


G. Physicians, patients have different views on walk-in visits  

A survey of 142 patients and the doctors who treated them revealed 61% of walk-in clinic visits were deemed appropriate by responding physicians, 20% were considered understandable and about 18% were of such low urgency that they could have waited for an appointment with the patient's regular physician. However, only 12% of responding patients considered their visits to be highly urgent, 55% thought their visits were of medium urgency and 33% considered their visits to be of low urgency.  


H. Vitamin E Slows Decline in Alzheimer's 

Older veterans with mild to moderate Alzheimer's disease who took vitamin E supplements in a randomized trial showed less progression of functional impairment, researchers said. 


I. Distracted Driving and Risk of Road Crashes 

January 2, 2014 | S.G. Klauer and Others  NEJM 

In a study of novice and experienced drivers in cars in which cameras and sensors had been installed, the authors found significant associations between secondary tasks (e.g., cell-phone dialing) and the risk of a crash or near-crash, particularly among novice drivers. 

Full-text (free—with cool 2-min video): http://www.nejm.org/doi/full/10.1056/NEJMsa1204142  

J. Mindfulness Meditation May Ease Depression, Anxiety, Pain 

A systematic review in JAMA Intern Med 2014 


K. How A Little Caffeine Can Boost Your Memory 

If you’re trying to commit a set of items to memory, you may want to give your brain a bit of caffeine. But how you time it matters, finds a new study out today in Nature Neuroscience. The researchers found that giving people caffeine after they memorized a series of pictures significantly boosted their ability to remember the subtler details, compared to people who’d been given dummy pills. Before you down a six-shot Americano, though, be aware that there’s a sweet spot: A 200-milligram dose of caffeine – about the amount in a large cup of coffee – was the only one to do the trick… 


L. Five Probiotic Drops a Day to Keep Infantile Colic Away? 

It worked in this RCT! 

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