Sunday, November 29, 2015

Lit Bits: Nov 29, 2015

From the recent medical literature...

1. A Little Satirical Levity

A. How Hospitalists and Emergency Physicians Can Learn to Work Together

About: ZDoggMD is a physician, off-white rapper, and the founder of Turntable Health. He’s not a businessman. He’s a business, man. OK we stole that line from Jay-Z but you get the idea. A hospitalist at Stanford for almost 10 years, Dr. Z currently resides in Las Vegas—a city he finds simply adorable.

B. The Idiosyncrasies and Frustrations of Conference Calls

Tripp and Tyler Video (4 min):

2. Emergency Medicine Code Black Documentary Basis for CBS TV Primetime Series

By ACEP Now, November 17, 2015

When ACEP Now last spoke with emergency physician and documentary filmmaker Ryan McGarry, MD, his film, Code Black, which chronicled life in the emergency department at University of Southern California Los Angeles County General Hospital, was receiving high praise on the documentary film circuit. Now, a year later, Code Black has made the jump from silver screen to television screens worldwide. CBS is currently airing a fictional drama series based on Dr. McGarry’s documentary Wednesdays at 10 p.m. Eastern/9 p.m. Central.

Dr. McGarry recently spoke with ACEP Now Medical Editor-in-Chief Kevin Klauer, DO, EJD, FACEP, about the process of bringing Code Black to TV and the show’s commitment to an honest and accurate portrayal of emergency medicine. Here are some highlights from their conversation.

3. Brief Lit Reviews from Ann Emerg Med

A. Does Ultrasonographic Guidance Reduce Failure Rates and Adverse Events for Subclavian Vein Catheterization Compared With the Landmark Technique?

Bottom Line: Yes! Compared with the landmark technique, dynamic 2-dimensional (2D) (real-time) ultrasonographic guidance increases the success rate and reduces adverse events in subclavian vein catheterization.

B. What Is the Risk of Symptomatic Intracerebral Hemorrhage in Patients With Stroke Mimics Who Receive Intravenous Thrombolytics?

Take-home: In studies of thrombolysis for ischemic stroke, some subjects receiving the drug for conditions mimicking stroke experienced intracranial hemorrhage, although this was less frequent than in patients treated for true stroke.

C. Is Extracorporeal Membrane Oxygenation More Effective Than Standard Measures in Critically Ill Adults?

Bottom Line: In critically ill adults with respiratory failure or cardiac arrest, there is currently insufficient evidence for the use of extracorporeal membrane oxygenation (ECMO).

D. Can Vasopressors Safely Be Administered Through Peripheral Intravenous Catheters Compared With Central Venous Catheters?

Take-home: Although the safety profile of peripheral administration of vasopressors remains uncertain, most reported adverse events are associated with a distal peripheral site or prolonged duration of administration.

E. Comparison of Early Goal-Directed Therapy With Usual Care for Severe Sepsis and Septic Shock

Bottom Line: Compared with unstructured usual care, early goal-directed therapy does not decrease mortality in patients with severe sepsis or septic shock.

4. Finding the fifth intercostal space for chest drain insertion: guidelines and ultrasound.

Bowness JS, et al. Emerg Med J. 2015 Dec;32(12):951-4.

OBJECTIVES: International guidelines exist for chest drain insertion and recommend identifying the fifth intercostal space or above, around the midaxillary line. In a recent study, applying these guidelines in cadavers risked insertion in the 6th intercostal space or below in 80% of cases. However, there are limitations of cadaveric studies and this investigation uses ultrasound to determine the intercostal space identified when applying these guidelines in healthy adult volunteers.

METHODS: On each side of the chest wall in 31 volunteers, the position for drain insertion was identified using the European Trauma Course method, Advanced Trauma Life Support (ATLS) method, British Thoracic Society's 'safe triangle' and the 'traditional' method of palpation. Ultrasound imaging was used to determine the relationship of the skin marks with the underlying intercostal spaces.

RESULTS: Five methods were assessed on 60 sides. In contrast to the cadaveric study, 94% of skin marks lay over a safe intercostal space. However, the range of intercostal spaces found spanned the second to the seventh space. In 44% of women, the inferior boundary of the 'safe triangle' and the ATLS guidelines located the sixth intercostal space or below.

CONCLUSIONS: Current guidelines often identify a safe site for chest drain insertion, although the same site is not reproducibly found. In addition, women appear to be at risk of subdiaphragmatic drain insertion when the nipple is used to identify the fifth intercostal space. Real-time ultrasonography can be used to confirm the intercostal space during this procedure, although a safe guideline is still needed for circumstances in which ultrasound is not possible.

5. Written Informed Consent for CT of the Abdomen/Pelvis is Associated with Decreased CT Utilization in Low-Risk ED Patients

Merck LH, et al. West J Emerg Med 2015 Nov 16 [Epub ahead of print]

Objective: The increasing rate of patient exposure to radiation from Computerized Tomography (CT) raises questions about appropriateness of utilization. There is no current standard to employ informed consent for CT (ICCT). Our study assessed the relationship between informed consent and CT utilization in Emergency Department patients.

Methods: An observational multiphase before-after cohort study was completed from 4/2010-5/2011. CT utilization was assessed before and after (Time I/ Time II) the implementation of an informed consent protocol. Adult patients were included if they presented with symptoms of abdominal/pelvic pathology or completed ED CT. Patients with pregnancy, trauma, or altered mental status were excluded. Data on history, exam, diagnostics, and disposition were collected via standard abstraction tool. A multivariate logistic model was generated via stepwise regression (SAS software v9.3), to assess CT utilization across risk groups. Logistic models, stratified by risk, were generated to include time period and a propensity score that controlled for potential confounders of CT utilization and time.

Results: 7,684 patients met inclusion criteria. At Time II, there was a 24% reduction in CT utilization in the low-risk patient group (p less than 0.002). ICCT did not affect CT utilization in the high-risk group (p=0.16). In low-risk patients, the propensity score was significant (p less than 0.001). There were no adverse events reported during the study period.

Conclusion: The implementation of ICCT was associated with reduced CT utilization in low-risk ED patients. ICCT has the potential to increase informed, shared decision making with patients, as well as to reduce the risks and cost associated with CT.

6. Expanded Testing for PE Leads CT Scan Overuse

Ryan Radecki. ACEP Now. Nov 18, 2015

In the vast ocean of medicine, few diagnostic dilemmas descend so quickly into madness as does pulmonary embolism (PE). In the classical teaching, PE remains one of a handful of life-threatening diagnoses considered in the context of chest pain or shortness of breath. The proliferation of advanced imaging technology has also dramatically eased evaluation for PE, leading to an explosion of testing. Sadly, the cumulative effect of such expanded testing appears to be a pervasive preponderance of negative studies and low-yield, but costly, utilization.

And, frankly, it’s even worse than we’ve acknowledged.

The vast majority of PEs are diagnosed using one test, the computed tomography (CT) pulmonary angiogram. This test gained widespread acceptance with the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) studies, demonstrating adequate sensitivity for PE compared with conventional angiography.1 Sensitivity is a valuable test attribute for a disease believed to have a high case-fatality rate. However, as technology has improved, CT has begun detecting smaller and smaller clots. By assigning the same clinical significance across the disease severity spectrum, it becomes unclear whether this improved sensitivity benefits our patients and whether our test specificity is adequate for our current strategy.

The problem is twofold, and two specialties are complicit in this predicament: radiology and emergency medicine. In radiology, the subsegmental PE is the culprit. As vessel size decreases, the quality of opacification and contrast capture diminishes. This results in consistent ambiguity regarding the presence of a flow-limiting lesion.

For example, a group of authors in Pennsylvania reviewed 415 images from their institution judged diagnostic for PE, focusing mostly on segmental and subsegmental PE.2 Using five radiologists, four of whom were subspecialty trained in thoracic radiology, each image was individually re-reviewed. Based on their sample of 192 images read initially as segmental PE, a majority of authors could not agree on a positive finding in 5.7 percent of cases. For subsegmental PE, at least one reviewer dissented in 60 percent of cases. When compared with the original community radiologist’s official read, the consensus was a false-positive rate of 3.6 percent for segmental PE and 15 percent for subsegmental PE.

A second radiology department, this time in Ireland, reviewed 174 CTs reported positive for PE.3 Three subspecialty-trained thoracic radiologists subsequently reviewed each of the studies read initially by one of 15 general radiologists. In this study, 45 (25.9 percent) cases were judged erroneously reported positive, including 26.8 percent segmental and 59.4 percent subsegmental. The authors reported the most common causes of diagnostic error were technical image-acquisition artifacts underappreciated by the general radiologists.

The authors offer a few specific suggestions relevant to radiologists to improve image quality and account for technical issues, but their primary complaint was simply this: we scanned too many patients who did not have a PE. After subtracting the patients with false-positives, yield in this study was 129 of 937, or 13.7 percent, falling at the low end of most published performance characteristics. This prompted another recommendation: the best way to improve yields is to refer patients for scan only when they have a higher pretest likelihood of disease.

Referring appropriate patients for CT is, unfortunately, something we do terribly in the United States. A comparison of populations of patients evaluated for PE in several observational studies, with 3,174 patients in Europe and 7,940 patients in the United States, showed patients were reliably higher risk in European populations.4 Interestingly, this was most exaggerated in the clinical gestalt of treating clinicians: in Europe only a third of patients were thought to be low risk, while in the United States these totaled nearly two-thirds. The net effect in this study was an overall yield for PE of 28.1 percent in Europe compared with 7.1 percent in the United States. The PEs diagnosed in the United States were also generally less severe as stratified by the Pulmonary Embolism Severity Index, and PE-related deaths were likewise lower. The concise summary: we’re performing astounding numbers of negative CTs and finding less significant disease, and it’s almost certain our already-low numbers of positive results are further diluted by false-positives.

Using a validated diagnostic strategy, grounded in sound risk assessment, can reduce excessive testing. The fantastic Ali Raja, MD, leads a team that recently published updated American College of Physicians clinical guidelines for the evaluation of patients with suspected acute PE.5 These guidelines include most of the same strategies espoused in ACEP’s prior guideline but now updated to include age-adjusted D-dimer.6 The age-adjusted threshold, age × 10 ng/mL added to the generic 500 ng/mL in patients older than age 50, has been validated in multiple studies. Most recently, a review of a large cohort of Kaiser Permanente patients revealed a small handful of additional missed PEs, but the corresponding decrease in radiation exposure and contrast-induced nephropathy provided a net benefit.7 These authors did not account for the likelihood of false-positive CTs in patients with low pretest probability, and it is reasonable to suggest their study overstates the excess misses while understating the harm reduction.

Looking further at how our emergency medicine experts view the evaluation for PE, Jeff Kline offers a comprehensive summary of risk factors and diagnostic considerations.8,9 In his view, nonspecific cardiopulmonary symptoms are not sufficient in isolation to reasonably consider the possibility of PE. Patients must have physiologic manifestations of PE absent an alternative cause, paired with the presence of at least one known risk factor for PE. Risk-stratification into low, intermediate, or high risk can be performed by gestalt, Wells score, or revised Geneva score. Low-risk patients who meet the PE rule-out criteria fulfill an unfavorable risk-to-benefit ratio, and testing should be avoided. For otherwise low- and intermediate-risk patients, quantitative D-dimer testing is recommended.

Better yet, Kline has also proposed dynamically adjusting the D-dimer cutoff level based on the pretest probability.10 In a review of 126 patients diagnosed with PE, there were 11 patients for whom the pretest likelihood of PE was low and who had D-dimer levels less than 1000 ng/mL. All but one was subsegmental, representing less than 5 percent of the pulmonary vascular tree, and none had concomitant deep venous thrombosis. Accounting for the risks of anticoagulation, the increasing prevalence of false-positive CT pulmonary arteriography, and the risks of contrast-induced nephropathy, it may yet prove reasonable to forgo CT in this subset of patients. However, until better evidence becomes available, such a strategy should be approached via shared decision making, balancing the risks of small, undiagnosed PE against those associated with anticoagulation.

As vessel size decreases, the quality of opacification and contrast capture diminishes. This results in consistent ambiguity regarding the presence of a flow-limiting lesion.

There is no question that widespread use of CT has provided substantial benefit to patients and the health care system. However, its ubiquity and ease of use is leading to unintended consequences, particularly in overdiagnosis paired with substantial risks of unnecessary treatment. Every effort should be made to reduce use of CT in those with low pretest likelihood of PE, and small, subsegmental PE should be viewed with suspicion in the context of individual patient factors. We must continue to refine and reflect upon our routine evaluation of cardiopulmonary complaints, lest our pursuit of this white whale slip into madness.

7. On the Prescribing of Oral Antibiotics

A. Should antibiotics be routinely used in patients with acute uncomplicated diverticulitis?

Isacson D, et al. Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study. Int J Colorectal Dis. 2015 Sep;30(9):1229-34.

PURPOSE: The aim of this study was to evaluate outpatient, non-antibiotic management in acute uncomplicated diverticulitis with regard to admissions, complications, and recurrences, within a 3-month follow-up period.

METHODS: A prospective, observational study in which patients with computer tomography-verified acute uncomplicated diverticulitis were managed as outpatients without antibiotics. The patients kept a personal journal, were contacted daily by a nurse, and then followed up by a surgeon at 1 week and 3 months.

RESULTS: In total, 155 patients were included, of which 54 were men; the mean age of the patients was 57.4 years. At the time of diagnosis, the mean C-reactive protein and white blood cell count were 73 mg/l and 10.5 × 10(9), respectively, and normalized in the vast majority of patients within the first week. The majority of the patients (97.4%) were managed successfully as outpatients without antibiotics, admissions, or complications. In only four (2.6%) patients, the management failed because of complications in three and deterioration in one. These patients were all treated successfully as inpatients without surgery. Five patients had recurrences and were treated as outpatients without antibiotics. Follow-up colonic investigations revealed cancer in two patients and polyps in 13 patients.

CONCLUSION: Previous results of low complication rates with the non-antibiotic policy were confirmed. The new policy of outpatient management without antibiotics in acute uncomplicated diverticulitis is now shown to be feasible, well functioning, and safe.

In support of this approach:

i. Chabok A, et al. AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 Apr;99(4):532-9.

ii. The new American Gastroenterological Association Institute Guideline on the Management of Acute Diverticulitis.

Stollman N, et al. Gastroenterol 2015 Oct 7 [Epub ahead of print]

In patients with CT-documented acute uncomplicated diverticulitis, the use of antibiotics does not seem to improve symptoms or decrease the need for surgery, and may not decrease the development of complications or recurrence rates. The AGA suggests that antibiotics should be used selectively, rather than routinely, in patients with uncomplicated disease. Conditional recommendation, low quality of evidence.              

Until recently, antibiotics have been the unquestioned cornerstone of treatment of acute diverticulitis, consistently recommended in prior guidelines, textbooks and expert reviews. An emerging conception that acute diverticulitis may be more inflammatory than infectious, and increasing concerns about the overuse of antibiotics, have led to preliminary investigations into the necessity of antibiotics. Two recent randomized trials and two systematic reviews have reported no clear benefit and questioned their routine use, as does this guideline, suggesting selective and individualized use. It is important to emphasize that the current data are of low quality, and recommendations could change as further studies are performed. Further the patients studied were inpatients with CT-confirmed uncomplicated disease; therefore, the results should not be generalized to complicated patients (i.e., those with abscesses or fistulas), those with signs of severe infection or sepsis, the immunosuppressed, or patients with other significant comorbidities. This recommendation is conditional due to the low quality of current evidence. Additionally, outpatient management without antibiotics has not been studied, although we would expect these patients to have generally milder disease and logically equal or better outcomes.

B. Doctor-patient discussions may cut antibiotic overprescribing

Shared decision-making between primary care physicians and patients helps reduce prescriptions for antibiotics to treat respiratory infections, according to a Cochrane Library report. When patients and doctors discuss the issue, 29% are prescribed antibiotics, compared with nearly 50% of clinical encounters that did not involve shared decision-making. The findings were based on over 1,000 doctors and hundreds of thousands of patients who participated in 10 randomized controlled trials in the UK and Europe.

C. Inappropriate Antibiotic Therapy in a Patient with Heart Failure and Prolonged QT Interval: A Teachable Moment of Torsades

Gupta A, et al. JAMA Intern Med. 2015;175(11):1748-1749.

This case illustrates how unnecessary antibiotic use might cause life-threatening adverse events in the context of certain types of heart disease.

8. FDA moves quickly to approve easy-to-use nasal spray to treat opioid overdose

Naloxone in nasal spray form provides important new alternative for family members, first responders

November 18, 2015

Today the U.S. Food and Drug Administration approved Narcan nasal spray, the first FDA-approved nasal spray version of naloxone hydrochloride, a life-saving medication that can stop or reverse the effects of an opioid overdose. Opioids are a class of drugs that include prescription medications such as oxycodone, hydrocodone, and morphine, as well as the illegal drug heroin.

Drug overdose deaths, driven largely by prescription drug overdoses, are now the leading cause of injury death in the United States – surpassing motor vehicle crashes. In 2013, the Centers for Disease Control and Prevention reported the number of drug overdose deaths had steadily increased for more than a decade. When someone overdoses on an opioid, it can be difficult to awaken the person, and breathing may become shallow or stop – leading to death if there is no medical intervention. If naloxone is administered quickly, it can counter the overdose effects, usually within two minutes.

“Combating the opioid abuse epidemic is a top priority for the FDA,” said Stephen Ostroff, M.D., acting commissioner, Food and Drug Administration. “We cannot stand by while Americans are dying. While naloxone will not solve the underlying problems of the opioid epidemic, we are speeding to review new formulations that will ultimately save lives that might otherwise be lost to drug addiction and overdose.” 

Until this approval, naloxone was only approved in injectable forms, most commonly delivered by syringe or auto-injector. Many first responders and primary caregivers, however, feel a nasal spray formulation of naloxone is easier to deliver, and eliminates the risk of a contaminated needle stick. As a result, there has been widespread use of unapproved naloxone kits that combine an injectable formulation of naloxone with an atomizer that can deliver naloxone nasally. Now, people have access to an FDA-approved product for which the drug and its delivery device have met the FDA’s high standards for safety, efficacy and quality.

Narcan nasal spray does not require assembly and delivers a consistent, measured dose when used as directed. This prescription product can be used on adults or children and is easily administered by anyone, even those without medical training. The drug is sprayed into one nostril while the patient is lying on his or her back, and can be repeated if necessary. However, it is important to note that it is not a substitute for immediate medical care, and the person administering Narcan nasal spray should seek further immediate medical attention on the patient’s behalf.

The FDA granted fast-track designation and priority review for Narcan nasal spray. Fast track is a process designed to facilitate development and expedite review of drugs intended to treat serious conditions and that demonstrate the potential to address an unmet medical need. The agency’s priority review program provides for an expedited review of drugs that offer a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. Narcan nasal spray is being approved in less than four months, significantly ahead of the product’s prescription drug user fee goal date of January 20, 2016.

In clinical trials conducted to support the approval of Narcan nasal spray, administering the drug in one nostril delivered approximately the same levels or higher of naloxone as a single dose of an FDA-approved naloxone intramuscular injection, and achieved these levels in approximately the same time frame.

“We heard the public call for this new route of administration, and we are happy to have been able to move so quickly on a product we are confident will deliver consistently adequate levels of the medication – a critical attribute for this emergency life-saving drug,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research.

Use of Nasal Naloxone in the Community

Walley AY, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013;346:f174.

CONCLUSIONS: Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.

9. High-frequency linear transducer improves transabdominal detection of an IUP in first trimester ultrasound.

Tabbut M et al. Am J Emerg Med 2015 Nov 3 [Epub ahead of print]

A third of transvaginal ultrasound exams were avoided by use of the high-frequency probe.

To determine if the need for transvaginal ultrasound examination can be decreased by the addition of the transabdominal high-frequency, 12–4 MHz linear transducer after a failed examination with the 6–2 mHz curvilinear transducer when evaluating for an intrauterine pregnancy (IUP).

This is a prospective pilot study of women in their first trimester of pregnancy presenting to the Emergency Department with abdominal pain and/or vaginal bleeding. If no IUP was identified using the curvilinear transducer via the transabdominal approach, they were subsequently scanned using the linear transducer. Patients without evidence of an IUP transabdominally were scanned via the transvaginal approach.

81 patients were evaluated and, no IUP was visualized in 27 using the standard curvilinear transducer approach and these then had an ultrasound performed with the linear transducer. Of these, 9 patients (33.3%, 0.95 CI 15.5-51.1%) were found to have an IUP with the linear transducer. For the 18 patients who received a transvaginal scan, 15 patients (83.3%, 0.95 CI 66.1-100%) had no IUP identified with the transvaginal transducer and 3 (16.7%, 0.95 CI 0–33.9%) had an IUP identified.

The transabdominal use of a high-frequency linear transducer in the evaluation of patients in the first trimester after failed curvilinear transducer results in a clinically significant reduction in the need for transvaginal ultrasonography to confirm the presence of an IUP.

10. Risk of Bacterial Meningitis in Children 6 to 11 Months of Age with a First Simple Febrile Seizure: A Retrospective, Cross-sectional, Observational Study.

Guedj R, et al. Acad Emerg Med. 2015 Nov;22(11):1290-7.

OBJECTIVES: National and international guidelines are very heterogeneous about the necessity to perform a lumbar puncture (LP) in children under 12 months of age with a first simple febrile seizure. We estimated the risk of bacterial meningitis in children aged 6 to 11 months with a first simple febrile seizure.

METHODS: This multicenter retrospective study was conducted in seven pediatric emergency departments (EDs) in the region of Paris, France. Visits of patients aged 6 to 11 months for a first simple febrile seizure from January 2007 to December 2011 were analyzed. Bacterial meningitis was sequentially sought for by 1) analyzing bacteriologic data at the time of the visit, 2) looking for data from a second visit to the hospital after the index visit, and 3) phone calling the child's parents to determine the symptom evolution after the index visit. Infants lost to this follow-up were searched for in a national bacterial meningitis database.

RESULTS: From a total of 1,183,487 visits in the seven pediatric EDs, 116,503 were for children 6 to 11 months of age. From these, 205 visits were for a first simple febrile seizure. An LP was performed in 61 patients (29.8%). The outcome bacterial meningitis was ascertainable for 168 (82%) visits. No bacterial meningitis was found among these patients (95% confidence interval = 0% to 2.2%). None of the 37 infants lost to our follow-up were registered in the national database as having bacterial meningitis.

CONCLUSIONS: Among children between 6 and 11 months of age with a first simple febrile seizure, the risk of bacterial meningitis is extremely low. These results should encourage national and international societies to either develop or endorse guidelines limiting routine LP in these infants and contribute to widely homogenized management practices.

11. Trial of Continuous or Interrupted Chest Compressions during CPR.

Nichol G, et al. N Engl J Med. 2015 Nov 9. [Epub ahead of print]

Background During cardiopulmonary resuscitation (CPR) in patients with out-of-hospital cardiac arrest, the interruption of manual chest compressions for rescue breathing reduces blood flow and possibly survival. We assessed whether outcomes after continuous compressions with positive-pressure ventilation differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations.

Methods This cluster-randomized trial with crossover included 114 emergency medical service (EMS) agencies. Adults with non-trauma-related cardiac arrest who were treated by EMS providers received continuous chest compressions (intervention group) or interrupted chest compressions (control group). The primary outcome was the rate of survival to hospital discharge. Secondary outcomes included the modified Rankin scale score (on a scale from 0 to 6, with a score of ≤3 indicating favorable neurologic function). CPR process was measured to assess compliance.

Results Of 23,711 patients included in the primary analysis, 12,653 were assigned to the intervention group and 11,058 to the control group. A total of 1129 of 12,613 patients with available data (9.0%) in the intervention group and 1072 of 11,035 with available data (9.7%) in the control group survived until discharge (difference, -0.7 percentage points; 95% confidence interval [CI], -1.5 to 0.1; P=0.07); 7.0% of the patients in the intervention group and 7.7% of those in the control group survived with favorable neurologic function at discharge (difference, -0.6 percentage points; 95% CI, -1.4 to 0.1, P=0.09). Hospital-free survival was significantly shorter in the intervention group than in the control group (mean difference, -0.2 days; 95% CI, -0.3 to -0.1; P=0.004).

Conclusions In patients with out-of-hospital cardiac arrest, continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions. (Funded by the National Heart, Lung, and Blood Institute and others; ROC CCC number, NCT01372748 .).

12. Images in Clinical Practice

Left Main Coronary Artery Stent Migration

Central Retinal-Vein Occlusion

Treponema pallidum — The Great Imitator

Tension Pneumoperitoneum

Man with Chest Pain

Young Boy with Shedding Nails

Discussion: That’s Some Weird Nail Polish You Got There!

Woman with Mass on Her Back

Woman with Abdominal Pain and Diarrhea

Amaurosis Fugax Caused by a Branch Retinal Artery Embolus

Mistaken STEMI

13. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity

Siegal DM, et al. N Engl J Med 2015 Nov 11 [Epub ahead of print]

Background Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors.

Methods Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti-factor Xa activity, which is a measure of factor Xa inhibition by the anticoagulant.

Results Among the apixaban-treated participants, anti-factor Xa activity was reduced by 94% among those who received an andexanet bolus (24 participants), as compared with 21% among those who received placebo (9 participants) (P less than 0.001), and unbound apixaban concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter (P less than 0.001); thrombin generation was fully restored in 100% versus 11% of the participants (P less than 0.001) within 2 to 5 minutes. Among the rivaroxaban-treated participants, anti-factor Xa activity was reduced by 92% among those who received an andexanet bolus (27 participants), as compared with 18% among those who received placebo (14 participants) (P less than 0.001), and unbound rivaroxaban concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter (P less than 0.001); thrombin generation was fully restored in 96% versus 7% of the participants (P less than 0.001). These effects were sustained when andexanet was administered as a bolus plus an infusion. In a subgroup of participants, transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed, which resolved within 24 to 72 hours. No serious adverse or thrombotic events were reported.

Conclusions Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects.

Editorial: Antidote for Factor Xa Anticoagulants

14. Can You Multitask? Evidence and Limitations of Task Switching and Multitasking in Emergency Medicine

Skaugset LM, et al. Ann Emerg Med 2015 Nov 13 [Epub ahead of print]

Emergency physicians work in a fast-paced environment that is characterized by frequent interruptions and the expectation that they will perform multiple tasks efficiently and without error while maintaining oversight of the entire emergency department. However, there is a lack of definition and understanding of the behaviors that constitute effective task switching and multitasking, as well as how to improve these skills. This article reviews the literature on task switching and multitasking in a variety of disciplines—including cognitive science, human factors engineering, business, and medicine—to define and describe the successful performance of task switching and multitasking in emergency medicine. Multitasking, defined as the performance of two tasks simultaneously, is not possible except when behaviors become completely automatic; instead, physicians rapidly switch between small tasks. This task switching causes disruption in the primary task and may contribute to error. A framework is described to enhance the understanding and practice of these behaviors.

15. Stroke risk stratification in acute dizziness presentations: A prospective imaging-based study.

Kerber KA, et al. Neurology. 2015 Oct 28 [Epub ahead of print]

OBJECTIVE: To estimate the ability of bedside information to risk stratify stroke in acute dizziness presentations.

METHODS: Surveillance methods were used to identify patients with acute dizziness and nystagmus or imbalance, excluding those with benign paroxysmal positional vertigo, medical causes, or moderate to severe neurologic deficits. Stroke was defined as acute infarction or intracerebral hemorrhage on a clinical or research MRI performed within 14 days of dizziness onset. Bedside information comprised history of stroke, the ABCD2 score (age, blood pressure, clinical features, duration, and diabetes), an ocular motor (OM)-based assessment (head impulse test, nystagmus pattern [central vs other], test of skew), and a general neurologic examination for other CNS features. Multivariable logistic regression was used to determine the association of the bedside information with stroke. Model calibration was assessed using low (less than 5%), intermediate (5% to less than 10%), and high (≥10%) predicted probability risk categories.

RESULTS: Acute stroke was identified in 29 of 272 patients (10.7%). Associations with stroke were as follows: ABCD2 score (continuous) (odds ratio [OR] 1.74; 95% confidence interval [CI] 1.20-2.51), any other CNS features (OR 2.54; 95% CI 1.06-6.08), OM assessment (OR 2.82; 95% CI 0.96-8.30), and prior stroke (OR 0.48; 95% CI 0.05-4.57). No stroke cases were in the model's low-risk probability category (0/86, 0%), whereas 9 were in the moderate-risk category (9/94, 9.6%) and 20 were in the high-risk category (20/92, 21.7%).

CONCLUSION: In acute dizziness presentations, the combination of ABCD2 score, general neurologic examination, and a specialized OM examination has the capacity to risk-stratify acute stroke on MRI.

16. Lidocaine with morphine for ED patients with acute renal colic improves nausea control: a double-blind, RCT

Firouzian A, et al. Amer J Emerg Med. 2015 November 18 [Epub ahead of print]

Renal colic (RC) is a common clinical presentation in the emergency department (ED). Prompt and effective pain control is one of the first responsibilities of emergency physicians. The aim of this study was to evaluate the analgesic effect of adding lidocaine to morphine compared to morphine alone in patients presenting to the ED with RC.

In a double-blind, randomized controlled trial a total of 110 adults’ patients of both sexes, aged 18-50 years, who presented to the ED with signs and symptoms suggestive of RC were randomly assigned into 1 of 2 groups. Patients in group A received morphine (0.1 mg/kg) plus lidocaine (1.5 mg/kg), while those in group B received morphine (0.1 mg/kg) plus normal saline 0.9% as placebo. All patients were asked to rate the intensity of their pain and nausea on a 0-10 point Visual Analogue Scale (VAS) at before and 5, 10, 30, 60, and 120 minutes after intervention.

There was a statistically significant time trend decline in both groups for both pain and nausea scores (P less than  0.01). Repeated measures analysis showed a significant effect for the interaction between group and time of persistent pain (P = 0.034), but there was no significant group effect in this regard (P = 0.146). Median times to being pain-free in the group receiving morphine plus lidocaine and in the group taking morphine alone were 87.02 minutes (95% CI: 74.23-94.82) and 100.12 minutes (95%CI: 89.95-110.23), respectively (P = 0.071). Repeated-measures analysis also showed a significant group effect for nausea (P = 0.038), but there was no interaction between group and time in this regard (P = 0.243). The median nausea-free times in the group receiving morphine plus lidocaine and the group receiving morphine alone were 26.6 minutes (95% CI: 14.16-39.03) and 58.33 minutes (95% CI: 41.85-74.82), respectively. This time difference was statistically significant (P less than  0.001).

Using lidocaine may be recommended as an effective, safe, and inexpensive adjuvant to morphine in improving nausea and reducing the time needed to achieve pain and nausea relief in patients visiting the ED with acute RC.

17. Identifying Patients Suitable for DC after a Single-Presentation High-Sensitivity Trop Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays.

Carlton EW, et al. Ann Emerg Med. 2015;66(6):635–645.e1

STUDY OBJECTIVE: We compare the ability of 5 established risk scores to identify patients with suspected acute coronary syndromes who are suitable for discharge after a modified single-presentation high-sensitivity troponin result.

METHODS: This was a prospective observational study conducted in a UK district general hospital emergency department. Consecutive adults recruited with suspected acute coronary syndrome for whom attending physicians determined evaluation with serial troponin testing was required. Index tests were definitions of low risk applied to modified Goldman, Thrombolysis in Myocardial Infarction (TIMI), Global Registry of Acute Cardiac Events (GRACE), History, ECG, Age, Risk Factors, Troponin (HEART), and Vancouver Chest Pain Rule risk scores, incorporating either high-sensitivity troponin T or I results. The endpoint was acute myocardial infarction within 30 days. A test sensitivity threshold for acute myocardial infarction of 98% was chosen. Clinical utility was defined as a negative predictive value greater than or equal to 99.5% and identification of greater than 30% suitable for discharge.

RESULTS: Nine hundred fifty-nine patients underwent high-sensitivity troponin T analysis and 867 underwent high-sensitivity troponin I analysis. In the high-sensitivity troponin T group, 79 of 959 (8.2%) had an acute myocardial infarction and 66 of 867 (7.6%) in the high-sensitivity troponin I group. Two risk scores (GRACE less than 80 and HEART ≤3) did not have the potential to achieve a sensitivity of 98% with high-sensitivity troponin T, and 3 scores (Goldman ≤1, TIMI ≤1, and GRACE less than 80) with high-sensitivity troponin I. A TIMI score of 0 or less than or equal to 1 and modified Goldman score less than or equal to 1 with high-sensitivity troponin T, and TIMI score of 0 and HEART score of less than or equal to 3 with high-sensitivity troponin I had the potential to achieve a negative predictive value greater than or equal to 99.5% while identifying greater than 30% of patients as suitable for immediate discharge.

CONCLUSION: With established risk scores, it may be possible to identify greater than 30% of patients suitable for discharge, with a negative predictive value greater than or equal to 99.5% for the diagnosis of acute myocardial infarction, using a single high-sensitivity troponin test result at presentation. There is variation in high-sensitivity troponin assays, which may have implications in introducing rapid rule-out protocols.

18. Accuracy of Peripheral Thermometers for Estimating Temperature: A Systematic Review and Meta-analysis.

Niven DJ, et al. Ann Intern Med. 2015 Nov 17;163(10):768-77.

BACKGROUND: Body temperature is commonly used to screen patients for infectious diseases, establish diagnoses, monitor therapy, and guide management decisions.

PURPOSE: To determine the accuracy of peripheral thermometers for estimating core body temperature in adults and children.

DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL Plus from inception to July 2015.

STUDY SELECTION: Prospective studies comparing the accuracy of peripheral (tympanic membrane, temporal artery, axillary, or oral) thermometers with central (pulmonary artery catheter, urinary bladder, esophageal, or rectal) thermometers.

DATA EXTRACTION: 2 reviewers extracted data on study characteristics, methods, and outcomes and assessed the quality of individual studies.

DATA SYNTHESIS: 75 studies (8682 patients) were included. Most studies were at high or unclear risk of patient selection bias (74%) or index test bias (67%). Compared with central thermometers, peripheral thermometers had pooled 95% limits of agreement (random-effects meta-analysis) outside the predefined clinically acceptable range (± 0.5 °C), especially among patients with fever (-1.44 °C to 1.46 °C for adults; -1.49 °C to 0.43 °C for children) and hypothermia (-2.07 °C to 1.90 °C for adults; no data for children). For detection of fever (bivariate random-effects meta-analysis), sensitivity was low (64% [95% CI, 55% to 72%]; I2 = 95.7%; P less than 0.001) but specificity was high (96% [CI, 93% to 97%]; I2 = 96.3%; P less than 0.001). Only 1 study reported sensitivity and specificity for the detection of hypothermia.

LIMITATIONS: High-quality data for some temperature measurement techniques are limited. Pooled data are associated with interstudy heterogeneity that is not fully explained by stratified and metaregression analyses.

CONCLUSION: Peripheral thermometers do not have clinically acceptable accuracy and should not be used when accurate measurement of body temperature will influence clinical decisions.

19. Comparison of Two Sepsis Recognition Methods in a Pediatric ED.

Balamuth F, et al. Acad Emerg Med. 2015 Nov;22(11):1298-306.

OBJECTIVES: The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED).

METHODS: This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared.

RESULTS: Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively.

CONCLUSIONS: The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities.

20. Prevalence and Clinical Import of Thoracic Injury Identified by Chest CT but Not CXR in Blunt Trauma: Multicenter Prospective Cohort Study.

Langdorf MI, et al. Ann Emerg Med 2015;66(6):589–600.

STUDY OBJECTIVE: Chest computed tomography (CT) diagnoses more injuries than chest radiography, so-called occult injuries. Wide availability of chest CT has driven substantial increase in emergency department use, although the incidence and clinical significance of chest CT findings have not been fully described. We determine the frequency, severity, and clinical import of occult injury, as determined by changes in management. These data will better inform clinical decisions, need for chest CT, and odds of intervention.

METHODS: Our sample included prospective data (2009 to 2013) on 5,912 patients at 10 Level I trauma center EDs with both chest radiography and chest CT at physician discretion. These patients were 40.6% of 14,553 enrolled in the parent study who had either chest radiography or chest CT. Occult injuries were pneumothorax, hemothorax, sternal or greater than 2 rib fractures, pulmonary contusion, thoracic spine or scapula fracture, and diaphragm or great vessel injury found on chest CT but not on preceding chest radiography. A priori, we categorized thoracic injuries as major (having invasive procedures), minor (observation or inpatient pain control over 24 hours), or of no clinical significance. Primary outcome was prevalence and proportion of occult injury with major interventions of chest tube, mechanical ventilation, or surgery. Secondary outcome was minor interventions of admission rate or observation hours because of occult injury.

RESULTS: Two thousand forty-eight patients (34.6%) had chest injury on chest radiography or chest CT, whereas 1,454 of these patients (71.0%, 24.6% of all patients) had occult injury. Of these, in 954 patients (46.6% of injured, 16.1% of total), chest CT found injuries not observed on immediately preceding chest radiography. In 500 more patients (24.4% of injured patients, 8.5% of all patients), chest radiography found some injury, but chest CT found occult injury. Chest radiography found all injuries in only 29.0% of injured patients. Two hundred and two patients with occult injury (of 1,454, 13.9%) had major interventions, 343 of 1,454 (23.6%) had minor interventions, and 909 (62.5%) had no intervention. Patients with occult injury included 514 with pulmonary contusions (of 682 total, 75.4% occult), 405 with pneumothorax (of 597 total, 67.8% occult), 184 with hemothorax (of 230 total, 80.0% occult), those with greater than 2 rib fractures (n=672/1,120, 60.0% occult) or sternal fracture (n=269/281, 95.7% occult), 12 with great vessel injury (of 18 total, 66.7% occult), 5 with diaphragm injury (of 6, 83.3% occult), and 537 with multiple occult injuries. Interventions for patients with occult injury included mechanical ventilation for 31 of 514 patients with pulmonary contusion (6.0%), chest tube for 118 of 405 patients with pneumothorax (29.1%), and 75 of 184 patients with hemothorax (40.8%). Inpatient pain control or observation greater than 24 hours was conducted for 183 of 672 patients with rib fractures (27.2%) and 79 of 269 with sternal fractures (29.4%). Three of 12 (25%) patients with occult great vessel injuries had surgery. Repeated imaging was conducted for 50.6% of patients with occult injury (88.1% chest radiography, 11.9% chest CT, 7.5% both). For patients with occult injury, 90.9% (1,321/1,454) were admitted, with 9.1% observed in the ED for median 6.9 hours. Forty-four percent of observed patients were then admitted (4.0% of patients with occult injury).

CONCLUSION: In a more seriously injured subset of patients with blunt trauma who had both chest radiography and chest CT, occult injuries were found by chest CT in 71% of those with thoracic injuries and one fourth of all those with blunt chest trauma. More than one third of occult injury had intervention (37.5%). Chest tubes composed 76.2% of occult injury major interventions, with observation or inpatient pain control greater than 24 hours in 32.4% of occult fractures. Only 1 in 20 patients with occult injury was discharged home from the ED. For these patients with blunt trauma, chest CT is useful to identify otherwise occult injuries.

21. Malpractice Litigation and Testicular Torsion: A Legal Database Review.

Colaco M, et al. J Emerg Med. 2015;49(6):849–854.

BACKGROUND: The litigious nature of the American medical environment is a major concern for physicians, with an estimated annual cost of $10 billion.

OBJECTIVE: The purpose of this study is to identify causes of litigation in cases of testicular torsion and what factors contribute to verdicts or settlements resulting in indemnity payments.

METHODS: Publicly available jury verdict reports were retrieved from the Westlaw legal database (Thomson Reuters, New York, NY). In order to identify pertinent cases, we used the search terms "medical malpractice" and "testicular torsion" with date ranging from 2000 to 2013. Jury verdicts, depositions, and narrative summaries were evaluated for their medical basis, alleged malpractice, findings, and indemnity payment(s) (if any).

RESULTS: Fifty-two cases were identified that were relevant to this study. Fifty-one percent of relevant cases were found in favor of the defendant physician, with the remaining 49% involving an indemnity payment (13% of which were settled). The most commonly sued medical providers were emergency physicians (48% of defendants), with urologists being second most common and making up 23% of the defendant pool. Emergency physicians were significantly more likely to make indemnity payments than urologists.

CONCLUSION: Testicular torsion is a delicate condition and requires expertise in evaluation and treatment. When emergency physicians choose not to consult an urologist for possible torsion, they leave themselves open to litigation risk. When an urologist is involved in torsion litigation, they are rarely unsuccessful in their defense. Finally, ultrasound is no guarantee for success against litigation.

22. Choose to Be Grateful. It Will Make You Happier.

Arthur C Brooks. New York Times. Nov 21, 2015

TWENTY-FOUR years ago this month, my wife and I married in Barcelona, Spain. Two weeks after our wedding, flush with international idealism, I had the bright idea of sharing a bit of American culture with my Spanish in-laws by cooking a full Thanksgiving dinner.

Easier said than done. Turkeys are not common in Barcelona. The local butcher shop had to order the bird from a specialty farm in France, and it came only partially plucked. Our tiny oven was too small for the turkey. No one had ever heard of cranberries.

Over dinner, my new family had many queries. Some were practical, such as, “What does this beast eat to be so filled with bread?” But others were philosophical: “Should you celebrate this holiday even if you don’t feel grateful?”

I stumbled over this last question. At the time, I believed one should feel grateful in order to give thanks. To do anything else seemed somehow dishonest or fake — a kind of bourgeois, saccharine insincerity that one should reject. It’s best to be emotionally authentic, right? Wrong. Building the best life does not require fealty to feelings in the name of authenticity, but rather rebelling against negative impulses and acting right even when we don’t feel like it. In a nutshell, acting grateful can actually make you grateful.

For many people, gratitude is difficult, because life is difficult. Even beyond deprivation and depression, there are many ordinary circumstances in which gratitude doesn’t come easily. This point will elicit a knowing, mirthless chuckle from readers whose Thanksgiving dinners are usually ruined by a drunk uncle who always needs to share his political views. Thanks for nothing.

Beyond rotten circumstances, some people are just naturally more grateful than others. A 2014 article in the journal Social Cognitive and Affective Neuroscience identified a variation in a gene (CD38) associated with gratitude. Some people simply have a heightened genetic tendency to experience, in the researchers’ words, “global relationship satisfaction, perceived partner responsiveness and positive emotions (particularly love).” That is, those relentlessly positive people you know who seem grateful all the time may simply be mutants.

But we are more than slaves to our feelings, circumstances and genes. Evidence suggests that we can actively choose to practice gratitude — and that doing so raises our happiness…

The remainder of the essay:

23. Book Recommendation

Sherry Turkle (MIT), Reclaiming Conversation: The Power of Talk in a Digital Age (New York: Penguin Press, 2015).

Renowned media scholar Sherry Turkle investigates how a flight from conversation undermines our relationships, creativity, and productivity—and why reclaiming face-to-face conversation can help us regain lost ground.

Sherry Turkle is Abby Rockefeller Mauzé Professor of the Social Studies of Science and Technology in the Program in Science, Technology, and Society at MIT and the founder (2001) and current director of the MIT Initiative on Technology and Self. Professor Turkle received a joint doctorate in sociology and personality psychology from Harvard University and is a licensed clinical psychologist.

24. Micro Bits

A. IT in the ED: Emergency Physicians Explore Their Inner Geeks

Emergency physicians tend to be the MacGyvers of the medical world. They must think quickly and decisively, maintain a wide variety of medical skills, and under stressful conditions find creative solutions to problems. So it seems natural that an emergency physician would not simply accept using a clunky information system that slows things down.

A new breed of emergency informaticists has emerged, and they’re educating themselves about what’s under the hood of their electronic medical record systems so they can be tweaked to do good instead of evil: to access key information about new patients, get tips on the best care, and document the visit, rather than introducing time-wasting and potentially dangerous steps into providers’ work flow.

Thus, we have the field of emergency informatics. Emergency physicians interested in a basic grounding in the topic have been taking the online 10×10 course in Biomedical and Health Informatics for Emergency Physicians, sponsored by Oregon Health & Science University. The 10×10 informatics course is designed for physicians and nurses of all backgrounds; an emergency medicine–specific version has been available for the past 5 years, in partnership with the American College of Emergency Physicians (ACEP) (which publishes this journal). The course culminates in an in-person session at the fall ACEP Scientific Assembly…

B. Lower BP targets may reduce risk of cardiac events, study finds

Data from the SPRINT trial showed a target systolic blood pressure of 120 reduced mortality, heart attack, heart failure and stroke rates, compared with the current recommendations of 140 for people younger than 60 and 150 for elderly patients. The study was presented at the American Heart Association annual meeting and published in the New England Journal of Medicine. A related report in the Journal of the American College of Cardiology estimates that at least 16.8 million Americans could benefit from therapy to reduce BP to the lower levels studied in the SPRINT trial.

C. Angioplasty does not improve stable heart disease outcomes, study finds

People with stable heart disease and chest pain should try medications and lifestyle modification before turning to angioplasty, according to findings published in the New England Journal of Medicine. The study followed patients for 15 years and found that patients who undergo angioplasty and stenting fare no better than those who make lifestyle changes and take a regimen of statins, hypertension drugs and aspirin. Researcher William Boden, M.D., said it's important that patients getting angioplasty understand it will not help them live longer or avoid a heart attack.

D. Exercise and Health: Dose and Response, Considering Both Ends of the Curve

Regular exercise is the most effective way to prevent disease; exercise also can help treat many of the chronic illnesses that plague America.47 Exercise is necessary for optimal health, and for health, moderate exercise is sufficient.

We know much more about the minimum daily requirement for exercise than about the maximum safe limit. But we do know that each individual does have a limit, which increases with proper training but decreases with age and when illness or injury intervenes. Individuals who choose to push toward their limit should do so with informed consent, knowing that some experts worry they may risk cardiac damage, while others believe intense exercise may attenuate the health benefits of more moderate exercise.

Walking, jogging, and running will all promote good health, but no one should mistake health as the reason to run a marathon. Still, there are valid personal reasons for high-level exercise; if marathon running seems right for you, just be sure to do it right.

Edward Stanley, the Earl of Derby, got it right in 1873 when he said that those who think they have not time for bodily exercise will sooner or later have to find time for illness.

E. Inpatient PPI use tied to infection, death risk

A study in the Journal of General Internal Medicine found that proton-pump inhibitors, frequently prescribed in hospital settings to prevent stomach bleeding, may be linked to greater mortality from hospital-acquired infections. The study used a simulation based on inpatient data to explore risk, finding that those who start PPIs while hospitalized have a 90% higher risk of death, while patients who previously took PPIs and continue during a hospital stay have 79% increased risk. Patients taking PPIs may develop pneumonia or Clostridium difficile infection.

F. CDC: Uninsured rate continues to decline

The proportion of Americans without health insurance was about 9% in the first half of this year, compared with 16% in 2010, according to the CDC's National Center for Health Statistics. About 28.5 million US residents were still without health insurance this year, the survey found.

G. Study links moderate coffee consumption to lower risk of death

Researchers found people who drank one to five cups of coffee daily, whether caffeinated, decaffeinated or both, were less likely to die from type 2 diabetes, heart disease, neurological diseases or suicide, but not cancer, compared with those who didn't drink coffee. The findings in Circulation were based on data from more than 200,000 participant.

H. Patients may benefit when surgical residents scrub in

There is no danger and it might even be beneficial to have surgical residents join senior physicians in the operating room, data show. Rates of complications were similar in cases that included residents, compared with those involving only senior physicians, and 30-day mortality risk was 7% lower, according to a study published in the Journal of the American College of Surgeons. Surgical residents may help attending surgeons to improve proper preoperative decision-making and act as an additional safety checkpoint, said senior study author Faek Jamali.

I. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children with a History of Such Illnesses: A RCT

J. Study highlights risks of off-label prescribing

About 12% of prescriptions written are off-label, and about 80% of those off-label prescriptions are not supported by strong scientific evidence, researchers report in JAMA Internal Medicine. Although no difference was seen in the side effect rates for on-label and off-label prescriptions backed by strong scientific evidence, the risk of adverse effects associated with off-label prescriptions not backed by strong scientific evidence was 54% higher than for on-label prescriptions supported by such evidence, the study found.