Monday, February 29, 2016

Lit Bits: Feb 29, 2016

From the recent medical literature...

1. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Singer M, et al. JAMA. 2016;315(8):801-810.

Importance  Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

Objective  To evaluate and, as needed, update definitions for sepsis and septic shock.

Process  A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).

Key Findings From Evidence Synthesis  Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.

Recommendations  Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (greater than 18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.

Conclusions and Relevance  These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

Editorial: New Sepsis Diagnostic Guidelines Shift Focus to Organ Dysfunction

Jacob, JA. JAMA 2016;315(8):739-740.

In March 2012, Rory Staunton, a 12-year-old boy in Queens, New York, cut his arm playing basketball in school. The next day, his parents, worried about his fever and leg pain, took him to see his pediatrician and then, the day after, to the emergency department at NYU Langone Medical Center. He was discharged with a diagnosis of an upset stomach and dehydration but died 3 days later from sepsis ( His parents later founded the Rory Staunton Foundation to increase public awareness of the condition (

Rory’s story illustrates the stealth and rapid progress of sepsis, which affects about 1 million people a year in the United States and kills about a quarter of those affected ( New guidelines published in this issue of JAMA, which are intended to increase the precision and speed of sepsis diagnosis, shift the diagnostic focus from infection with systemic inflammation to infection-triggered organ dysfunction, eliminate the distinction between sepsis and severe sepsis, and refine the definition of septic shock (Singer M et al. JAMA. 2016;315[8]:801-810).

A 19-member joint task force of the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) developed the guidelines through expert consensus and literature review, as well as by studying data from 1.3 million electronic health record (EHR) encounters of patients with suspected infections who were treated at 12 hospitals within the University of Pittsburgh Medical Center system from January 1, 2010, to December 31, 2012. Data were also analyzed for an additional 706 399 patients from 4 EHR data sets within and outside of the United States.

Based on the assessment of the content validity, literature review, and expert deliberation, the task force defined sepsis as a “life-threatening organ dysfunction caused by a dysregulated host response to infection” (Singer M et al. JAMA. 2016;315[8]:801-810).

“[The task force] felt very strongly that we needed to differentiate a straightforward infection from one that can cause organ dysfunction or death,” said Mervyn Singer, MD, the guidelines’ co-lead author and director of the Bloomsbury Institute for Intensive Care Medicine at University College London. He explained that this new emphasis on organ dysfunction, rather than infection, stems from an evolving understanding of the pathophysiology of sepsis that encompasses both inflammatory and anti-inflammatory responses and coagulation, metabolic, and hormonal changes. Such changes cause a dysregulated response to infection and can lead to organ dysfunction.

In addition, the systemic inflammatory response syndrome (SIRS) criteria, which have been used to diagnose sepsis for more than 20 years, can occur in normal disease processes such as the common cold or even when a person vigorously exercises.

“[Sepsis] is much more nuanced than previously appreciated,” explained Derek Angus, MD, MPH, one of the guidelines’ coauthors and a professor and chair of the department of critical care medicine at the University of Pittsburgh School of Medicine. “Certain parts of the inflammatory response are overactive, and some are underactive.”…

More from Sepsis-3

A. Assessment of Clinical Criteria for Sepsis

This cohort study uses health system and research cohort data to compare the ability of existing vs new clinical criteria for sepsis to identify intensive care unit patients with suspected infection at higher mortality risk.

B. New Definition and Criteria for Septic Shock

This article describes the results of a meta-analysis of criteria used to identify adults with septic shock and the processes by which a critical care task force used the results to revise current septic shock definitions.

2. Effectiveness of Patient Choice in Nonoperative vs Surgical Management of Pediatric Uncomplicated Acute Appendicitis

Minneci PC, et al.

JAMA Surg. Published online December 16, 2015.

Importance  Current evidence suggests that nonoperative management of uncomplicated appendicitis is safe, but overall effectiveness is determined by combining medical outcomes with the patient’s and family’s perspective, goals, and expectations.

Objective  To determine the effectiveness of patient choice in nonoperative vs surgical management of uncomplicated acute appendicitis in children.

Design, Setting, and Participants  Prospective patient choice cohort study in patients aged 7 to 17 years with acute uncomplicated appendicitis presenting at a single pediatric tertiary acute care hospital from October 1, 2012, through March 6, 2013. Participating patients and families gave informed consent and chose between nonoperative management and urgent appendectomy.

Interventions  Urgent appendectomy or nonoperative management entailing at least 24 hours of inpatient observation while receiving intravenous antibiotics and, on demonstrating improvement of symptoms, completion of 10 days of treatment with oral antibiotics.

Main Outcomes and Measures  The primary outcome was the 1-year success rate of nonoperative management. Successful nonoperative management was defined as not undergoing an appendectomy. Secondary outcomes included comparisons of the rates of complicated appendicitis, disability days, and health care costs between nonoperative management and surgery.

Results  A total of 102 patients were enrolled; 65 patients/families chose appendectomy (median age, 12 years; interquartile range [IQR], 9-13 years; 45 male [69.2%]) and 37 patients/families chose nonoperative management (median age, 11 years; IQR, 10-14 years; 24 male [64.9%]). Baseline characteristics were similar between the groups. The success rate of nonoperative management was 89.2% (95% CI, 74.6%-97.0%) at 30 days (33 of 37 children) and 75.7% (95% CI, 58.9%-88.2%) at 1 year (28 of 37 children). The incidence of complicated appendicitis was 2.7% in the nonoperative group (1 of 37 children) and 12.3% in the surgery group (8 of 65 children) (P = .15). After 1 year, children managed nonoperatively compared with the surgery group had fewer disability days (median [IQR], 8 [5-18] vs 21 [15-25] days, respectively; P less than .001) and lower appendicitis-related health care costs (median [IQR], $4219 [$2514-$7795] vs $5029 [$4596-$5482], respectively; P = .01).

Conclusions and Relevance  When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery.

3. In-Hospital Outcomes and Costs Among Patients Hospitalized During a Return Visit to the ED

Sabbatini AK, et al. JAMA. 2016 Feb 16;315(7):663-71.

IMPORTANCE: Unscheduled short-term return visits to the emergency department (ED) are increasingly monitored as a hospital performance measure and have been proposed as a measure of the quality of emergency care.

OBJECTIVE: To examine in-hospital clinical outcomes and resource use among patients who are hospitalized during an unscheduled return visit to the ED.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of adult ED visits to acute care hospitals in Florida and New York in 2013 using data from the Healthcare Cost and Utilization Project. Patients with index ED visits were identified and followed up for return visits to the ED within 7, 14, and 30 days.

EXPOSURES: Hospital admission occurring during an initial visit to the ED vs during a return visit to the ED.

MAIN OUTCOMES AND MEASURES: In-hospital mortality, intensive care unit (ICU) admission, length of stay, and inpatient costs.

RESULTS: Among the 9,036,483 index ED visits to 424 hospitals in the study sample, 1,758,359 patients were admitted to the hospital during the index ED visit. Of these patients, 149,214 (8.5%) had a return visit to the ED within 7 days of the index ED visit, 228,370 (13.0%) within 14 days, and 349,335 (19.9%) within 30 days, and 76,151 (51.0%), 122,040 (53.4%), and 190,768 (54.6%), respectively, were readmitted to the hospital. Among the 7,278,124 patients who were discharged during the index ED visit, 598,404 (8.2%) had a return visit to the ED within 7 days, 839,386 (11.5%) within 14 days, and 1,205,865 (16.6%) within 30 days. Of these patients, 86,012 (14.4%) were admitted to the hospital within 7 days, 121,587 (14.5%) within 14 days, and 173,279 (14.4%) within 30 days. The 86,012 patients discharged from the ED and admitted to the hospital during a return ED visit within 7 days had significantly lower rates of in-hospital mortality (1.85%) compared with the 1,609,145 patients who were admitted during the index ED visit without a return ED visit (2.48%) (odds ratio, 0.73 [95% CI, 0.69-0.78]), lower rates of ICU admission (23.3% vs 29.0%, respectively; odds ratio, 0.73 [95% CI, 0.71-0.76]), lower mean costs ($10,169 vs $10,799; difference, $629 [95% CI, $479-$781]), and longer lengths of stay (5.16 days vs 4.97 days; IRR, 1.04 [95% CI, 1.03-1.05]). Similar outcomes were observed for patients returning to the ED within 14 and 30 days of the index ED visit. In contrast, patients who returned to the ED after hospital discharge and were readmitted had higher rates of in-hospital mortality and ICU admission, longer lengths of stay, and higher costs during the repeat hospital admission compared with those admitted to the hospital during the index ED visit without a return ED visit.

CONCLUSIONS AND RELEVANCE: Compared with adult patients who were hospitalized during the index ED visit and did not have a return visit to the ED, patients who were initially discharged during an ED visit and admitted during a return visit to the ED had lower in-hospital mortality, ICU admission rates, and in-hospital costs and longer lengths of stay. These findings suggest that hospital admissions associated with return visits to the ED may not adequately capture deficits in the quality of care delivered during an ED visit.

4. False negative interpretations of cranial CT in aneurysmal SAH.

Mark DG, et al. Acad Emerg Med. 2016 Feb 26 [Epub ahead of print].

OBJECTIVES: Prior studies examining the sensitivity of cranial computed tomography (CT) for the detection of subarachnoid hemorrhage (SAH) have used the final radiology report as the reference standard. However, optimal sensitivity may have been underestimated due to misinterpretation of reportedly normal cranial CTs. This study aims to estimate the incidence of missed CT evidence of SAH among a cohort of patients with aneurysmal SAH (aSAH).

METHODS: We performed a retrospective chart review of emergency department (ED) encounters within an integrated health delivery system between January 2007 and June 2013 to identify patients diagnosed with aSAH. All initial non-contrast CTs from aSAH cases diagnosed by lumbar puncture (LP) and angiography following a reportedly normal non-contrast cranial CT (CT-negative aSAH) were then reviewed in a blinded, independent fashion by two board-certified neuroradiologists to assess for missed evidence of SAH. Reviewers rated the CT studies as having either definite evidence of SAH, probable evidence of SAH, or no evidence of SAH. Control patients who underwent a negative evaluation for aSAH based on cranial CT and LP results were also included at random in the imaging review cohort.

RESULTS: A total of 452 cases of aSAH were identified; 18 (4%) were cases of CT-negative aSAH. Of these, 7 (39%) underwent cranial CT within six hours of headache onset, and 2 (11%) had their initial CTs formally interpreted by board-certified neuroradiologists. Blinded independent CT review revealed concordant agreement for either definite or probable evidence of SAH in 9 out of 18 (50%) cases overall, and in 5 of the 7 (71%) CTs performed within six hours of headache onset. Inter-rater agreement was 83% for definite SAH and 72% for either probable or definite SAH.

CONCLUSIONS: CT evidence of SAH was frequently present but unrecognized according to the final radiology report in cases of presumed CT-negative aSAH. This finding may help explain some of the discordance between prior studies examining the sensitivity of cranial CT for SAH.

5. Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction

Nehme Z, et al. Heart 2016 Mar;102(6):444-51.

OBJECTIVE: Supplemental oxygen therapy may increase myocardial injury following ST-elevation myocardial infarction (STEMI). In this study, we aimed to evaluate the effect of the dose and duration of oxygen exposure on myocardial injury after STEMI.

METHODS: Descriptive analysis of data from a multicentre, prospective, randomised, controlled trial of 441 patients with STEMI randomised to supplemental oxygen therapy or room air breathing. The primary endpoint was myocardial infarct size as assessed by cardiac biomarkers, troponin (cTnI) and creatine kinase (CK). Oxygen therapy was commenced by paramedics, and continued for up to 12 h postintervention in hospital. Supplemental oxygen exposure was calculated as the area under the dose×time curve for oxygen administration over the first 12 h, and then assessed for its association with cTnI/CK release using multivariable linear regression.

RESULTS: The median supplemental oxygen exposure was 1746 L (IQR: 960-2858). After adjustment for potential confounders, every 100 L increase in oxygen exposure in the first 12 h was associated with a 1.4% (95% CI 0.6% to 2.2%, p less than 0.001) and 1.2% (95% CI 0.7% to 1.8%, p less than 0.001) increase in the mean peak cTnI and CK, respectively. Excluding patients who developed cardiogenic shock, recurrent myocardial infarction or desaturations (SpO2 less than 94%) during admission, every 100 L increase in oxygen exposure was associated with a 1.2% (95% CI 0.2% to 2.1%, p=0.01) and 1.0% (95% CI 0.3% to 1.7%, p=0.003) increase in the mean peak cTnI and CK, respectively. The median supplemental oxygen exposure of 1746 L would result in a 21% (95% CI 3% to 37%) increase in infarct size according to the cTnI profile.

CONCLUSIONS: Supplemental oxygen exposure in the first 12 h after STEMI was associated with a clinically significant increase in cTnI and CK release.

6. Myth busted: Fever not common symptom of teething

A study in Pediatrics found the most common symptoms of teething in children include irritated gums, irritability and drooling but not fever. Researchers analyzed data from 16 studies and found tooth eruption could cause temperature to increase but it could not be characterized as fever.

Massignan C, et al. Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis. Pediatrics 2016 Mar [Epub ahead of print]

CONTEXT: Symptoms associated with the primary tooth eruption have been extensively studied but it is still controversial.

OBJECTIVE: To assess the occurrence of local and systemic signs and symptoms during primary tooth eruption.

DATA SOURCES: Latin American and Caribbean Health Sciences, PubMed, ProQuest, Scopus, and Web of Science were searched. A partial gray literature search was taken by using Google Scholar and the reference lists of the included studies were scanned.

STUDY SELECTION: Observational studies assessing the association of eruption of primary teeth with local and systemic signs and symptoms in children aged 0 to 36 months were included.

DATA EXTRACTION: Two authors independently collected the information from the selected articles. Information was crosschecked and confirmed for its accuracy.

RESULTS: A total of 1179 articles were identified, and after a 2-phase selection, 16 studies were included. Overall prevalence of signs and symptoms occurring during primary tooth eruption in children between 0 and 36 months was 70.5% (total sample = 3506). Gingival irritation (86.81%), irritability (68.19%), and drooling (55.72%) were the most frequent ones.

LIMITATIONS: Different general symptoms were considered among studies. Some studies presented lack of confounding factors, no clear definition of the diagnostics methods, use of subjective measures and long intervals between examinations.

CONCLUSIONS: There is evidence of the occurrence of signs and symptoms during primary tooth eruption. For body temperature analyses, eruption could lead to a rise in temperature, but it was not characterized as fever.

7. Risk of delayed ICH in anticoagulated patients after minor head trauma: the role of repeat cranial CT.

Swap C, et al. Perm J. 2016 Feb 15 [Epub ahead of print].

Context: Patients receiving anticoagulant medications who experience minor head injury are at increased risk of an intracerebral hemorrhage (ICH) developing, even after an initial computed tomography (CT) scan of the brain yields normal findings. Conflicting evidence exists regarding the frequency at which delayed bleeding occurs.

Objective: To identify the frequency of delayed traumatic ICH in patients receiving warfarin or clopidogrel.

Design: We performed a retrospective observational study of adult trauma encounters for anticoagulated patients undergoing head CT at 1 of 13 Kaiser Permanente Southern California Emergency Departments (EDs) between 2007 and 2011. Encounters were identified using structured data from electronic health and administrative records, and then records were individually reviewed for validation of results.

Main Outcome Measures: The primary outcome measure was ICH within 60 days of an ED visit with a normal head CT result.

Results: Our sample included 443 (260 clopidogrel and 183 warfarin) eligible ED encounters with normal findings of initial head CT. Overall, 11 patients (2.5%, 95% confidence interval [CI] = 1.4%-4.4%) had a delayed ICH, and events occurred at similar rates between the clopidogrel group (6/260, 2.3%, CI 1.1%-5.0%) and warfarin group (5/183, 2.7%, CI 1.2%-6.2%).

Conclusion: Trauma patients in the ED who are receiving warfarin or clopidogrel have approximately a 2.5% risk of delayed ICH after an initial normal finding on a head CT.

8. Brief Lit Reviews from Ann Emerg Med

A. Are Antibiotics Effective in the Treatment of Acute Maxillary Sinusitis?

Moderate evidence suggests that antibiotics provide a small clinical benefit for the treatment of acute maxillary sinusitis, defined as a maxillary sinus infection with an onset of fewer than 4 weeks. However, approximately 80% of patients improve within 2 weeks without any antibiotic treatment.

B. Does Intubation Improve Outcomes Over Supraglottic Airways in Adult Out-of-Hospital Cardiac Arrest?

In observational studies, intubation is associated with better outcomes than supraglottic airway devices in out-of-hospital cardiac arrest; however, the results of ongoing prospective trials are needed to confirm these findings.

C. Is Single-Dose Etomidate Induction Safe in Emergency Intubation of Critically Ill Patients?

Single-use etomidate in intubation for critically ill patients may result in transient adrenal and other organ dysfunction, but with no effect on mortality.

9. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

Glauser T, et al. Epilepsy Currents 2016;

The following organizations have endorsed this guideline: Epilepsy Foundation, Child Neurology Society, American College of Emergency Physicians, Association of Child Neurology Nurses, American Association of Neuroscience Nurses.

The analysis addressed five questions involving adults/children with seizures lasting more than 5 minutes:

Q1. Which anticonvulsants are efficacious as initial and subsequent therapy?
Q2. What adverse events are associated with anticonvulsant administration?
Q3. Which is the most effective benzodiazepine?
Q4. Is IV fosphenytoin more effective than IV phenytoin?
Q5. When does anticonvulsant efficacy drop significantly (i.e., after how many different anticonvulsants does status epilepticus become refractory)?

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear.

OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm.

DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists.

STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes.

DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm.

RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A).

Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm.

CONCLUSIONS: Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

10. Images in Clinical Practice

Scalp Necrosis Associated with Giant-Cell Arteritis

Geographic Tongue

Central Pontine Myelinolysis

Adult Female With Dyspnea

Elderly Man With Acute Respiratory Distress

Young Man With Lump in His Neck

Discussion of Neck Lump: The Lowdown on Ventriculoperitoneal Shunts

Adult Female With Chest Pain

Child With Chest Pain Diagnosed With Pneumonia

Newborn Infant With Respiratory Distress

Man With Finger Injury

Ocular Rosacea

Eggshell Calcifications of the Bladder

Shot in the Heart

A Rare Cause of Headache

Tension Hydrothorax Related to Disseminated Endometriosis

11. Apneic oxygenation is associated with a reduction in the incidence of hypoxemia during the RSI of patients with ICH in the ED.

Sakles JC, et al. Intern Emerg Med. 2016 Feb 4. [Epub ahead of print]

Critically ill patients undergoing emergent intubation are at risk of oxygen desaturation during the management of their airway. Patients with intracranial hemorrhage (ICH) are particularly susceptible to the detrimental effects of hypoxemia. Apneic oxygenation (AP OX) may be able to reduce the occurrence of oxygen desaturation during the emergent intubation of these patients. We sought to assess the effect AP OX on oxygen desaturation during the rapid sequence intubation (RSI) of patients with ICH in the emergency department (ED).

We prospectively collected data on all patients intubated in an urban academic ED over the 2-year period from July 1, 2013 to June 30, 2015. Following each intubation, the operator completed a standardized continuous quality improvement (CQI) data form, which included information on patient, operator and intubation characteristics. Operators recorded data on the use of AP OX, the oxygen flow rate used for AP OX, and the starting and lowest saturations during intubation. Adult patients with ICH who underwent RSI by emergency medicine (EM) residents were included in the analyses. The primary outcome variable was any oxygen saturation less than 90 % during the intubation. We performed a backward stepwise multivariate logistic regression analysis to identify variables associated with oxygen desaturation. The primary independent variable of interest was the use of AP OX during the intubation.

Inclusion criteria for the study was met by 127 patients. AP OX was used in 72 patients (AP OX group) and was not used in 55 patients (NO AP OX group). The incidence of desaturation was 5/72 (7 %) in the AP OX group and was 16/55 (29 %) in the NO AP OX group. In the multivariate logistic regression analysis the use of AP OX was associated with a reduced odds of desaturation (aOR 0.13; 95 % CI 0.03-0.53). Patients with ICH who received AP OX during RSI in the ED were seven times less likely to have an oxygen saturation of less than 90 % during the intubation compared to patients who did not receive AP OX.

AP OX is a simple intervention that may minimize the risk of oxygen desaturation during the RSI of patients with ICH.

12. ST depression in lead aVL differentiates inferior ST-elevation MI from pericarditis.

Bischof JE, et al. Am J Emerg Med. 2016 Feb;34(2):149-54.

BACKGROUND: ST-segment elevation (STE) due to inferior STE myocardial infarction (STEMI) may be misdiagnosed as pericarditis. Conversely, this less life-threatening etiology of ST elevation may be confused for inferior STEMI. We sought to determine if the presence of any ST-segment depression in lead aVL would differentiate inferior STEMI from pericarditis.

METHODS: Retrospective study of 3 populations. Cohort 1 included patients coded as inferior STEMI, cohort 2 included patients with a discharge diagnosis of pericarditis who presented with chest pain and at least 0.5 mm of ST elevation in at least 1 inferior lead. We analyzed the presenting electrocardiogram in both populations, with careful assessment of leads II, III, aVF, and aVL. In addition, we retrospectively studied a third cohort of patients with subtle inferior STEMI (less than 1-mm STE with occluded artery on catheterization) and assessed the sensitivity of ST depression in lead aVL for this group.

RESULTS: Of 154 inferior STEMI patients, 154 had some amount of ST depression in lead aVL (100%; confidence interval, 98%-100%). Of the 49 electrocardiograms in the pericarditis group, all 49 had some inferior STE but none had any ST-segment depression in lead aVL (specificity, 100%; confidence interval, 91%-100%). In the third cohort, there were 272 inferior MIs with coronary occlusion, of which 54 were "subtle." Of these, 49 had some ST depression in lead aVL.

CONCLUSION: When there is inferior ST-segment elevation, the presence of any ST depression in lead aVL is highly sensitive for coronary occlusion in inferior myocardial infarction and very specific for differentiating inferior myocardial infarction from pericarditis.

13. Ask Your Doctor if This Ad Is Right for You: How advertising promotes expensive drugs and treatments you may not need.

By Elisabeth Rosenthal. New York Times. FEB. 27, 2016

A LITTLE more than a decade ago, most health care advertising was confined to mass-market drugs, and hospitals and doctors generally considered the practice tacky or ethically dubious. More often than not, the ads appeared in unassuming places like cheaper women’s magazines or the New York subway — for decades New Yorkers sat beneath ubiquitous rainbow posters for Dr. Jonathan Zizmor that promised to conquer blemishes: 212-594-SKIN!

But today, health care advertising is skyrocketing and likely to turn up in business-class lounges in airport terminals or the Jitney to the Hamptons. It occupies the center spreads and back covers of elite magazines alongside plugs for luxury watches, jewelry and resorts. On television it has found its way into prime-time slots: presidential debates, primary campaign coverage and even the Super Bowl.

The ads are targeting a far more rarefied market than in the past: patients with good insurance or those who can pay out of pocket for the priciest drugs. Hospitals and clinics have also jumped into the fray: What hospital or clinic these days doesn’t trumpet its services to its customer base (people formerly known as patients)?

Drug companies, which once focused mainly on promoting products like painkillers that might be prescribed to millions, now advertise costly niche medicines that might be prescribed to thousands. Ads from the medical profession don’t focus on small-bore items like Dr. Z’s blemish remedies, but big-ticket treatments like joint replacements and cancer care.

The health care industry spent $14 billion on advertising in 2014, according to Kantar Media, a jump of nearly 20 percent since 2011. That includes over-the-counter medications, but not sponsorships (the Super Bowl had two health care systems as partners). While magazine advertising has dropped off somewhat with the withering of the publishing industry, television advertising has risen 55 percent for hospitals and 30 percent for prescription drugs in that period.

“The stage is beyond crowded, and everyone wants to be seen as shaping their brand and being the patients’ partner of choice,” said Lisa Kerins, a managing director at the Nielsen Company, who said that ad spending for hospitals had increased by 33 percent since the beginning of 2012.

Last weekend’s episode of “60 Minutes,” for example, included advertising for four expensive drugs and two hospitals, Memorial Sloan Kettering Cancer Center and NYU Langone Medical Center. Meanwhile, The New York Times Magazine on the same weekend featured glossy full-page promotions for hospitals in New York, Denver and Boston, competing for space with ads for spas and hotels…

14. Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial.

Rainer TH, et al. Ann Intern Med. 2016 Feb 23 [Epub ahead of print]

Background: Two recent double-blind randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations.

Objective: To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout.

Design: Multicenter, double-blind, randomized equivalence trial. Patients were randomly assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN registry number: ISRCTN45724113).

Setting: Four EDs in Hong Kong.

Participants: 416 patients aged 18 years or older.

Measurements: Analgesic effectiveness was defined as changes in pain (at rest or with activity) greater than 13 mm on a 100-mm visual analogue scale. Outcomes were measured during the first 2 hours in the ED and from days 1 to 14.

Results: 376 patients completed the study. Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major adverse events occurred during the study. During the ED phase, patients in the indomethacin group had more minor adverse events than those in the prednisolone group (19% vs. 6%; P less than 0.001). During days 1 to 14, 37% of patients in each group had minor adverse events.

Limitation: Diagnosis of gout was usually based on clinical criteria rather than examination of joint fluid.

Conclusion: Oral prednisolone and indomethacin had similar analgesic effectiveness among patients with acute gout. Prednisolone is an effective and safe first-line option for treatment of acute gout.

15. Point-of-Care Multi-Organ Ultrasound Improves Diagnostic Accuracy in Adults Presenting to the ED with Acute Dyspnea

Mantuani D, et al. West J Emerg Med. 2016;17(1):46-53.

Introduction: Determining the etiology of acute dyspnea in emregency department (ED) patients is often difficult. Point-of-care ultrasound (POCUS) holds promise for improving immediate diagnostic accuracy (after history and physical), thus improving use of focused therapies. We evaluate the impact of a three-part POCUS exam, or “triple scan” (TS) – composed of abbreviated echocardiography, lung ultrasound and inferior vena cava (IVC) collapsibility assessment – on the treating physician’s immediate diagnostic impression.

Methods: A convenience sample of adults presenting to our urban academic ED with acute dyspnea (Emergency Severity Index 1, 2) were prospectively enrolled when investigator sonographers were available. The method for performing components of the TS has been previously described in detail. Treating physicians rated the most likely diagnosis after history and physical but before other studies (except electrocardiogram) returned. An investigator then performed TS and disclosed the results, after which most likely diagnosis was reassessed. Final diagnosis (criterion standard) was based on medical record review by expert emergency medicine faculty blinded to TS result. We compared accuracy of pre-TS and post-TS impression (primary outcome) with McNemar’s test. Test characteristics for treating physician impression were also calculated by dichotomizing acute decompensated heart failure (ADHF), chronic obstructive pulmonary disease (COPD) and pneumonia as present or absent.

Results: 57 patients were enrolled with the leading final diagnoses being ADHF (26%), COPD/asthma (30%), and pneumonia (28%). Overall accuracy of the treating physician’s impression increased from 53% before TS to 77% after TS (p=0.003). The post-TS impression was 100% sensitive and 84% specific for ADHF.

Conclusion: In this small study, POCUS evaluation of the heart, lungs and IVC improved the treating physician’s immediate overall diagnostic accuracy for ADHF, COPD/asthma and pneumonia and was particularly useful to immediately exclude ADHF as the cause of acute dyspnea.

16. ED Prescription Opioids May Contribute to Risk for Addiction

A. ED Prescription Opioids as an Initial Exposure Preceding Addiction.

Butler MM, et al. Ann Emerg Med. 2016 Feb 10. [Epub ahead of print]

STUDY OBJECTIVE: Opioid abuse and overdose constitute an ongoing health emergency. Many presume opioids have little potential for iatrogenic addiction when used as directed, particularly in short courses, as is typical of the emergency department (ED) setting. We preliminarily explore the possibility that initial exposure to opioids by EDs could be related to subsequent opioid misuse.

METHODS: This cross-sectional study surveyed a convenience sample of patients reporting heroin or nonmedical opioid use at an urban, academic ED. We estimated the proportion whose initial exposure to opioids was a legitimate medical prescription and the proportion of those prescriptions that came from an ED. Secondary measurements included the proportion of patients receiving nonopioid substances before initial opioid exposure, the source of opioids between initial exposure and onset of regular nonmedical use, and time from initial prescription to opioid use disorder.

RESULTS: Of 59 subjects, 35 (59%; 95% confidence interval [CI] 47% to 71%) reported they were first exposed to opioids by a legitimate medical prescription, and for 10 of 35 (29%; 95% CI 16% to 45%), the prescription came from an ED. Most medically exposed subjects (28/35; 80%; 95% CI 65% to 91%) reported nonopioid substance use or treatment for nonopioid substance use disorders preceding the initial opioid exposure. Emergency providers were a source of opioids between exposure and onset of regular nonmedical use in 11 of 35 cases (31%; 95% CI 18% to 48%). Thirty-one of the 35 medically exposed subjects reported the time of onset of nonmedical use; median time from exposure to onset of nonmedical use was 6 months for use to get high (N=25; interquartile range [IQR] 2 to 36), 12 months for regular use to get high (N=24; IQR 2 to 36), 18 months for use to avoid withdrawal (N=26; IQR 2 to 38), and 24 months for regular use to avoid withdrawal (N=27; IQR 2 to 48). Eleven subjects (36%; 95% CI 21% to 53%) began nonmedical use within 2 months, and 9 of 11 (82%; 95% CI 53% to 96%) reported nonopioid substance use or treatment for alcohol abuse before initial opioid exposure.

CONCLUSION: Although short-term opioid administration by emergency providers is unlikely to cause addiction by itself, ED opioid prescriptions may contribute to the development of addiction in some patients. There is an urgent need for further research to estimate long-term risks of short-course opioid therapy so that the risk of iatrogenic addiction can be appropriately balanced with the benefit of analgesia.

B. Extent and Impact of Opioid Prescribing for Acute Occupational Low Back Pain in the ED

Lee SS, et al. J Emerg Med. 2016 Mar;50(3):376-384.e2

BACKGROUND: Initial management of acute occupational low back pain (AOLBP) commonly occurs in the emergency department (ED), where opioid prescribing can vary from the clinical guidelines that recommend limited use.

OBJECTIVE: The objective of this study was to explore how opioids are prescribed in the ED and the impact on work disability and other outcomes in AOLBP.

METHODS: A retrospective cohort study was conducted. All acute compensable lost-time LBP cases seen initially in the ED with a date of injury from January 1, 2009 to December 31, 2011 were identified within a nationally representative Workers' Compensation dataset. Multivariate models estimated the effect of early opioids (received within 2 days of ED visit) on disability duration, long-term opioid use, total medical costs, and subsequent surgeries.

RESULTS: Of the cohort (N = 2887), 12% received early opioids; controlling for severity, this was significantly associated with long-term opioid use (adjusted risk ratio = 1.29; 95% confidence interval 1.05-1.58) and increased total medical costs for those in the highest opioid dosage quartile, but not associated with disability duration or subsequent low back surgery.

CONCLUSIONS: Early opioid prescribing in the ED for uncomplicated AOLBP increased long-term opioid use and medical costs, and should be discouraged, as opioid use for low back pain has been associated with a variety of adverse outcomes. However, ED providers may be becoming more compliant with current LBP treatment guidelines.

17. Antibiotic Therapy for Adults Hospitalized With Community-Acquired Pneumonia: A Systematic Review

Lee JS, et al.  JAMA. 2016;315(6):593-602

Importance  Antibiotic therapy is the cornerstone of medical management for community-acquired pneumonia.

Objective  To assess the associations between 3 key aspects of antibiotic therapy (optimal time to antibiotic initiation, initial antibiotic selection, and criteria for the transition from intravenous to oral therapy) and short-term mortality in adults hospitalized with community-acquired pneumonia.

Evidence Review  Bibliographic databases of MEDLINE, EMBASE, and the Cochrane Collaboration were searched for studies of adults hospitalized with radiographically confirmed community-acquired pneumonia published from January 1, 1995, until November 5, 2015.

Findings  Twenty studies (17 observational and 3 randomized trials) met eligibility criteria. Among 8 observational studies identified, the 4 largest (study populations of 2878 to 1 170 022) found that antibiotic initiation within 4 to 8 hours of hospital arrival was associated with relative reductions of 5% to 43% in mortality; the 4 smallest studies (study populations of 451 to 2076) found no associations between the timing of antibiotic initiation and mortality. One cluster randomized trial (n = 1737) demonstrated noninferiority of β-lactam monotherapy (n = 506) vs β-lactam plus macrolide combination therapy (n = 566), with an absolute adjusted difference of 2.5% (90% CI, −0.6% to 5.2%) in 90-day mortality favoring β-lactam monotherapy. A second randomized trial (n = 580) failed to demonstrate noninferiority of β-lactam monotherapy vs β-lactam plus macrolide combination therapy, with an absolute difference of 7.6% (1-sided 90% CI upper limit, 13.0%) in attainment of clinical stability on hospital day 7 favoring β-lactam plus macrolide combination therapy. Six of 8 observational studies (study populations of 1188 to 24 780) found that β-lactam plus macrolide combination therapy was associated with relative reductions of 26% to 68% in short-term mortality and all 3 observational studies (study populations of 2068 to 24 780) reported that fluoroquinolone monotherapy was associated with relative reductions of 30% to 43% in mortality compared with β-lactam monotherapy. One randomized trial (n = 302) reported significantly reduced hospital length of stay (absolute difference, 1.9 days; 95% CI, 0.6 to 3.2 days), but no differences in treatment failure when objective clinical criteria were used to decide when to transition patients from intravenous to oral therapy.

Conclusions and Relevance  In adults hospitalized with community-acquired pneumonia, antibiotic therapy consisting of β-lactam plus macrolide combination therapy or fluoroquinolone monotherapy initiated within 4 to 8 hours of hospital arrival was associated with lower adjusted short-term mortality, supported predominantly by low-quality observational studies. One randomized trial supports the use of objective clinical criteria to guide the transition from intravenous to oral antibiotic therapy.

18. Adjunctive Dexamethasone worsened outcomes in HIV-Associated Cryptococcal Meningitis

Beardsley J, et al. N Engl J Med. 2016 Feb 11;374(6):542-54.

BACKGROUND: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis.

METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole.

RESULTS: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P less than 0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites.

CONCLUSIONS: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo.

19. Assessment of Common Preoxygenation Strategies Outside of the OR Environment.

Groombridge C, et al. Acad Emerg Med. 2016 Jan 4  [Epub ahead of print]

OBJECTIVES: Preoxygenation prior to intubation aims to increase the duration of safe apnea by causing denitrogenation of the functional residual capacity, replacing this volume with a reservoir of oxygen. In the operating room (OR) the criterion-standard for preoxygenation is an anesthetic circuit and well-fitting face mask, which provide a high fractional inspired oxygen concentration (FiO2 ). Outside of the OR, various strategies exist to provide preoxygenation. The objective was to evaluate the effectiveness of commonly used preoxygenation strategies outside of the OR environment.

METHODS: This was a prospective randomized unblinded study of 30 healthy staff volunteers from a major trauma center emergency department (ED) in Sydney, Australia. The main outcome measure is fractional expired oxygen concentration (FeO2 ) measured after a 3 minute period of tidal volume breathing with seven different preoxygenation strategies.

RESULTS: The mean FeO2 achieved with the anesthetic circuit was 81.0% (95% CI = 78.3% to 83.6%), bag-valve-mask (BVM) 80.1% (95% CI = 76.5% to 83.6%), BVM with nasal cannulae (NC) 74.8% (95% CI = 72.0% to 77.6%), BVM with positive end expiratory pressure valve (PEEP) 78.9% (95% CI = 75.4% to 82.3%), BVM + NC + PEEP 75.5% (95% CI = 72.2% to 78.9%), non-rebreather mask (NRM) 51.6% (95% CI = 48.8% to 54.4%), and NRM + NC 57.1% (95% CI = 52.9% to 61.2%). Preoxygenation efficacy with BVM strategies was significantly greater than NRM strategies (p less than 0.01), and non-inferior to the anesthetic circuit.

CONCLUSIONS: In healthy volunteers, the effectiveness of BVM preoxygenation was comparable to the anesthetic circuit (criterion standard), and superior to preoxygenation with NRM. The addition of nasal cannulae oxygen, PEEP, or both, did not improve the efficacy of the BVM device.

20. Frequency of Fractures Identified on Post-Reduction Radiographs after Shoulder Dislocation

Gottlieb M, et al. West J Emerg Med 2016;17(1):35-8.

Introduction: Most emergency physicians routinely obtain shoulder radiographs before and after shoulder dislocations. However, currently there is limited literature demonstrating how frequently new fractures are identified on post-reduction radiographs. The primary objective of this study was to determine the frequency of new, clinically significant fractures identified on post-reduction radiographs with a secondary outcome assessing total new fractures identified.

Methods: We conducted a retrospective chart review using appropriate International Classification of Diseases, 9th Revision (ICD-9) codes to identify all potential shoulder dislocations that were reduced in a single, urban, academic emergency department (ED) over a five-year period. We excluded cases that required operative reduction, had associated proximal humeral head or shaft fractures, or were missing one or more shoulder radiograph reports. All charts were abstracted separately by two study investigators with disagreements settled by consensus among three investigators. Images from indeterminate cases were reviewed by a radiology attending physician with musculoskeletal expertise. The primary outcome was the percentage of new, clinically significant fractures defined as those altering acute ED management. Secondary outcomes included percentage of new fractures of any type.

Results: We identified 185 total patients meeting our study criteria. There were no new, clinically significant fractures on post-reduction radiographs. There were 13 (7.0%; 95% CI [3.3%-10.7%]) total new fractures identified, all of which were without clinical significance for acute ED management.

Conclusion: Post-reduction radiographs do not appear to identify any new, clinically significant fractures. Practitioners should re-consider the use of routine post-reduction radiographs in the ED setting for shoulder dislocations.

21. Prospective comparison of ultrasound and CXR for confirmation of central vascular catheter placement

Weekes AJ, et al. Emerg Med J  2016;33:176-180  

Objective To prospectively compare ultrasound (US) versus CXR for confirmation of central vascular catheter (CVC) placement. Secondary objective was to determine the incidence of pneumothorax (PTX) and compare US with CXR completion times.

Methods Investigators performed the US saline flush echo test, and evaluated each anterior hemithorax for pleural sliding with US after subclavian or internal jugular CVC placement.

Measurements and main results 151 total (135 in the emergency department, 16 in the intensive care unit) patients after CVC placement, mean age 62.1±15.6 years and 83 (55%) female patients. The rapid atrial swirl sign ( RASS) was ultrasound finding of an immediate appearance of turbulence entering the right atrium via superior vena cava after a rapid saline flush of the distal CVC port. RASS was considered ‘negative’ for CVC malposition. US identified all correct CVC placements. Four suboptimal CVC tip placements were detected by CXR. US identified three of these misplacements (McNemar exact p value above 0.99). There were no cases of PTX or abnormal pleural sliding by either CXR or US. Median times for US and CXR completion were 1.1 (IQR 0.7) minutes and 20 (IQR: 30) minutes, respectively, median difference 23.8 (95% CI 19.6 to 29.3) minutes, p less than 0.0001.

Conclusions PTX and CVC tip malposition were rare after US-guided CVC placement. There was no significant difference between saline flush echo and CXR for the identification of catheter tip malposition. Benefits of US assessment for complications include reduced radiation exposure and time delays associated with CXR.

22. Studies of the New Oral Anticoagulants

A. An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.

Data from 8 poison control centers show no bleeding in cases of single ingestions of apixaban or rivaroxaban.

Spiller HA, et al. Ann Emerg Med. 2016 Feb;67(2):189-95.

STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban.

METHODS: A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set.

RESULTS: There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history did not predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L.

CONCLUSION: Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.

B. Volume and functional outcome of ICH according to oral anticoagulant type.

In an observational study, intracerebral hemorrhages were less severe with the newer agents than with warfarin.

Wilson D, et al. Neurology. 2016 Jan 26;86(4):360-6.

OBJECTIVE: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH.

METHODS: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors.

RESULTS: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037).

CONCLUSIONS: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH.

23. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

Peyvandi F, et al. N Engl J Med. 2016 Feb 11;374(6):511-22.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high.

METHODS: Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses.

RESULTS: Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group.

CONCLUSIONS: Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo.

24. Risk of Procedural Hemorrhage

Wolfe KS, et al. Thorax. 2 February 2016 [Epub ahead of print]

Critically ill and hospitalized patients often require invasive procedures as a part of their medical care. Each procedure carries a unique set of risks and associated complications, but common to all of them is the risk of hemorrhage. Central venous catheterization, arterial catheterization, paracentesis, thoracentesis, tube thoracostomy and lumbar puncture constitute a majority of the procedures performed in hospitalized patients. We will discuss the risk factors for bleeding complications from each of these procedures and methods to minimize risk. The correction of coagulopathy prior to procedures is often employed by clinicians to decrease bleeding risk, but there is minimal evidence to support this practice.

The summary evidence available at this time indicates that CVC placement carries similar risk in patients with and without abnormalities of hemostasis. Accordingly, we recommend the following strategies for CVC placement to minimize risk of bleeding: 1.) presence of an experienced operator, 2.) use of real-time ultrasound guidance for all CVC placement, … 4.) avoidance of routine prophylactic transfusions in mild to moderate disorders of hemostasis.

A recent review of a series of studies involving both adult and pediatric populations found that 39 LPs were performed at a platelet count less than 10,000/µL, 204 at counts between 11-20,000/0µL, 817 between 21-50,000/µL, and 858 between 51-100,000/µL. There were no bleeding complications in any of the studies.61 A separate review found a correlation between an abnormal coagulation status and hemorrhagic complications of LP, but it is unclear if other risk factors were present and what constituted an abnormal coagulation status.63 Given the paucity of data regarding optimal platelet levels for LP and the potential risks of hematoma, consensus guidelines recommend [proceeding with the procedure with] platelets of 50,000/µL or greater, with clinical judgment guiding practice when platelets fall between 20-49,000/µL.61

Related articles:
Bleeding complications of central venous catheterization in septic patients with abnormal hemostasis. Am J Emerg Med. 2014 Jul;32(7):737-42.

The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol. 2010;148(1):15-25.
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25. Dr. Dustin Ballard’s Medically Clear: Medical findings aren’t always true

Marin Independent Journal. 02/28/16, 4:18 PM

Perhaps you read in the New York Times about the slew of promising anti-aging drugs in development. Metformin (Glucophage) is one example.

Metformin has been used since the 1920s to help control diabetics’ blood sugar levels but it may actually do much more — perhaps prolonging life in diabetics and non-diabetics alike. Purportedly, metformin modulates metabolism and cellular damage through its effects on the liver controlling glucose (sugar) production. Biologically plausible? Yes. But do I advise adding metformin to your regiment of medications and supplements? Not so fast.

Before you start popping metformin, or whatever trendy supplement or super food, it is worth considering the spotty record of science’s record in discovering truth.

It’s an unfortunate reality that many biomedical research “findings” are ultimately proven to be illusory. This goes for drugs (remember when Vioxx was considered a safe treatment for arthritis?), dietary associations (oat bran to prevent heart disease?) and diagnostics (when exactly should you start getting mammograms?) How frequently do facts become fiction? Well, sadly, quite frequently — in fact, “findings” in medical research may be only slightly more reliable than Donald Trump’s “facts” and only about as good as sport pundit “expert” picks against the spread.

Feeling doubtful? Here’s a look at the evidence behind medical evidence.

First, let’s define what we mean by a “research finding.” A research finding is any relationship discovered in a study that meets the criteria for statistical significance. The typical standard for this is a “p value” of less than 0.05, which essentially means that there is only a 1-in-20 chance that the research finding was by chance rather than a real association. But while 95 percent confidence in the truth of a finding may seem intuitively appealing, there’s evidence that it may not be conservative enough.

Consider a 2005 paper by John P.A. Ioannidis, “Why most published research findings are false.” Ioannidis builds a theoretic model of the chances of obtaining a true research finding starting with sample size (how many patients are in the study) and p-value. He then mixes in additional terms to account for possible confounders that could cause a finding to be falsely true. These include investigator bias (recognized or not); the probability, prior to study, of the association being true, and the number of different possible associations being tested.

From his model, he concludes that the chances of a finding being a true finding range from about 85 percent to lower than 20 percent! Eighty-five percent if the study was a well-controlled randomized trial of an association with reasonably high pre-study odds of being true; 20 percent or less if the study was retrospective (backwards looking) and examined rather broad associations such as diet and disease (think processed meat and cancer risk) or thousands of associations at once (think genetic-discovery-oriented research where 30,000 genes may be tested to find 30 or so true culprits).

Subsequent theoretic analyses have lent support to Ioannidis’ notion and generalize that no better than 50 percent of research findings are actually correct.

Indeed, in our recent history, there is a litany of research findings that could not be replicated or were outright refuted, such as the Lancet’s vaccines-cause-autism study. As such, the topic of how to distinguish the truth from the false positive has picked up considerable steam.

If this has you feeling skeptical about the health recommendations you receive and the value of biomedical research, you are not alone. Fortunately, this is not a presidential debate situation where all conclusions should be considered false until impartially verified. There are principles that can help both researchers and the public arrive at a better state of biomedical knowledge. And here’s where you come in: Do not simply assume that all research follows the following principles, be an informed consumer and learn to assess the quality of the “findings” you hear in the news.

So, here are those principles:

• Look for numbers; bigger is better. The work of Ioannidis and others has demonstrated that small numbers of observations or study subjects are more likely to have spurious results and be non-replicable. Place more credence in studies that have thousands, or tens of thousands of subjects rather than those with just a handful.

• Be wary of bias. Any studies published by entities with possible conflicts of interest or on a topic of newsy interest have a higher chance of false findings. This is not to say that every drug company study is rigged, but caution is advised in interpretation.

• Perform a “Does it makes sense?” test. The probability of a particular truth in medicine before a study is done greatly affects the likelihood of a finding being actually true. This principle is known as face validity. For example, just because some people who eat a lot of ice cream are thin does not mean that ice cream is an effective weight loss tool.

• Ask if the findings are randomized and replicated. In 2015, there were a series of studies, all randomized trials that demonstrated the benefit of a new clot retrieval technique for certain types strokes. All employed the best type of study design (randomized controlled trial) and had strongly positive results that were repeated in multiple other separate investigations. We can believe these results.

• Five sigma. Different scientific disciplines use different thresholds for defining a research finding. In medicine, the threshold is 2 sigma, which is two standard deviations or 95 percent confidence. In physics, however, it is 5 sigma, which equates to 99.99 percent confidence. If you see a finding in medicine that meets this 5 sigma criteria, you better believe that Sir Isaac Newton would approve.

So, before you start popping metformin, or whatever trendy supplement or super food, it is worth considering the spotty record of science’s record in discovering truth. Fortunately, you can also take heart in the fact that science remains the most vigorous supervisor of its own truths — false findings are discovered and discarded, and the total body of evidence moves forwards. It may be messy, but ultimately, it gets it right the vast majority of the time.

26. Micro Bits

A. Children may benefit from receiving asthma meds before discharge

Children with asthma were 78% less likely to return to the emergency department for additional treatment within 30 days after doctors implemented a "Meds in Hand" program at Boston Medical Center for two years. The program provides an in-room delivery service so patients do not need to go to another pharmacy. The study was published in Pediatrics.

B. Telemedicine project connects non-urgent ED patients with primary care physicians

The Army is testing a telemedicine program that connects non-emergency patients who come to the emergency department at Blanchfield Army Community Hospital in Fort Campbell, Ky., with primary care physicians at Eisenhower Army Medical Center in Augusta, Ga. The program's goals include reducing ED workloads and making sure non-emergency patients get timely access to care.