Monday, March 23, 2015

Lit Bits: Mar 23, 2015

1. Thrombolysis in acute ischaemic stroke: time for a rethink?

A. Evidence Shaky for Efficacy beyond 3 Hours

Alper BS, et al. BMJ 2015;350:h1075

As the UK regulator reviews alteplase in ischaemic stroke, Brian Alper and colleagues interpret the evidence to suggest increased mortality with uncertain benefit for its use beyond three hours

Systematic reviews and guidelines conclude that thrombolysis with alteplase (t-PA) up to 4.5 hours after the onset of ischaemic stroke is beneficial. It is reported to increase the likelihood of being functionally independent and not increase the 90 day risk of mortality. In the US the licence, or marketing authorisation, for alteplase is limited to 0-3 hours after onset of stroke,1 but some other countries—including the UK and Australia—have extended the licence to 4.5 hours.2 3 4 

Irrespective of licensing, most major stroke guidelines support use of alteplase up to 4.5 hours after stroke onset,5 6 7 8 9 10 11 12 13 14 15 16 although several emergency medicine associations do not recommend it (box).17 18 19 20 21

We believe that current guidance is based on uncertain evidence and that urgent reconsideration of the available data is essential to guide policy decisions on use of alteplase to manage acute stroke. In the UK the Medicines and Healthcare Regulatory Agency is planning to establish an expert working group to analyse all relevant sources of evidence and reassess the balance of benefits and risks for alteplase.22

We examined the most comprehensive sources of evidence and advice that working clinicians are likely to turn to for guidance on whether to use alteplase after stroke: a national clinical practice guideline published in 2013,5 the Cochrane review updated in 2014,23 and an individual patient data meta-analysis published in 2014.24 Each of these sources suggests that alteplase is more beneficial than harmful when given 3-4.5 hours after the onset of ischaemic stroke. We tried to verify the data supporting these conclusions. We do not examine evidence or recommendations for the use of alteplase up to three hours after stroke…

The remainder of the review (full-text free):

B. ACEP — Minus the Neurologists — Tempers its tPA Policy

Shaw G. Emerg Med News. 2015;37(3):1,33

A draft of a new clinical policy from the American College of Emergency Physicians (ACEP) takes a much more conservative approach on using intravenous tPA for managing acute ischemic stroke in the emergency department than the current guidelines, which were approved in 2012.

Those guidelines provoked a fair amount of controversy, with some emergency physicians saying the treatment was too risky and had little potential for benefit. (“The ‘Biggest, Baddest’ Controversy in EM,” EMN 2013;35[4]:1;

A year later, an article in the British Medical Journal questioned the reliability of the guidelines, calling them more industry marketing than tools of evidence-based medicine. (2013;346:f3830.) That report also questioned some of the committee members' conflicts of interest, some undeclared, and the “committee stacking” of the joint American Academy of Neurology-ACEP panel with experts with known viewpoints on a particular side of an issue. Seven of eight members of the AAN-ACEP committee, the BMJ article said, had previously spoken or written on the benefits of tPA for stroke, and “[n]ot one skeptic was included on the panel.” (“Conflicts of Interest on Guidelines Ramp Up tPA Controversy,” EMN 2013;35[10]:1;

ACEP announced last year that it would begin working on an independent policy on tPA for stroke, and that result, now in draft form, diverges from the policy it formulated with the AAN. In answer to critical question 1, “Is IV tPA safe and effective for acute ischemic stroke patients if given within 3 hours of symptom onset?” the 2015 draft, obtained by Emergency Medicine News, offers the following recommendations:

Level A recommendations. The increased risk of symptomatic intracerebral hemorrhage (approximately 7% compared to a baseline of 1%) must be considered when deciding whether to administer IV tPA to acute ischemic stroke patients.

Level B recommendations. With a goal to improve functional outcomes, IV tPA may be given to carefully selected acute ischemic stroke patients within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication.

Level C recommendations. Shared decision-making between the patient (and/or their surrogate) and a member of the healthcare team must include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation.)” (Download the draft at

The front-loading of hemorrhage risk as a level A recommendation and the cautious “may be given to carefully selected acute ischemic stroke patients” language in the level B recommendation stand in stark contrast to the 2012 document, which does not mention the increased risk of ICH in response to critical question 1 at all. Instead, it says: “In order to improve functional outcomes, IV tPA should be offered to acute ischemic stroke patients who meet National Institute of Neurological Disorders and Stroke (NINDS) inclusion/exclusion criteria and can be treated within 3 hours after symptom onset.” (Italics added.)

Members of the ACEP tPA policy subcommittee, chaired by Michael D. Brown, MD, MSc, declined to comment on the draft because it is still being reviewed, and they noted that revisions are likely before it is submitted to the ACEP Board of Directors for consideration, something they speculated should happen by June.

Non-committee members, however, weren't reluctant to share their opinions. David Newman, MD, the director of clinical research in emergency medicine at Mt. Sinai School of Medicine in New York City, praised the draft as a “tremendous improvement” in process and content.
“The process of developing this policy has been and is transparent. Anybody can take a good look at how the document was developed step-by-step, and that wasn't the case before,” he said. “This is an immense leap forward, and I think everybody's happy about that, whether they agree or disagree with the actual product. People are happy that the process adheres to the IOM's standards for the development of clinical practice guidelines.” …

2. Lost in Translation: Physician Understanding and Communication of Risk to Patients with Possible ACS Is Unacceptable and in Dire Need of Resuscitation

Hess EP. Ann Emerg Med. 2015 Mar 6 [Epub ahead of print]

In this (forthcoming) issue of Annals, Newman et al1 (link to abstract below) reports the results of a matched-pair survey study designed to assess risk communication between physicians and patients being admitted to the hospital for possible acute coronary syndrome. Four hundred twenty-five such patients and their physicians completed matched-pair surveys querying perceived and communicated current risk for myocardial infarction and future risk of mortality from myocardial infarction at home versus in the hospital. Post hoc application of risk prediction models on the patient cohort indicated a mean risk for death or myocardial infarction of less than 2% within 30 days. Physicians’ median estimate of 30-day adverse event risk was 5% (95% confidence interval 3% to 7%), and patients’ median estimate was 8% (95% confidence interval 5% to 11%). Despite physicians’ lower median estimate of risk, 63% of patients reported that their estimate of risk remained the same or increased after speaking with their physician. Patients’ median estimate of mortality risk after myocardial infarction was 80% if they were to go home and 10% if they were to stay in the hospital; physicians corresponding risk estimates were 15% and 10%, respectively. So not only did both physicians and patients substantially overestimate the current risk of myocardial infarction and future risk of mortality but also the data suggest poor physician communication in that agreement between patients and physicians did not improve after discussion.

What is one to make of these data? Despite several validated approaches to assessing patients’ short-term risk of major adverse cardiac events that are readily available and feasible to calculate,2-5 physicians’ risk estimates in this study were grossly inaccurate. These data suggest that physicians are not using validated prediction models in their usual clinical practice. In the absence of reliable, quantifiable risk estimates to guide decisionmaking, by process of elimination other factors must be influencing decisionmaking in regard to patients with possible acute coronary syndrome, such as one’s usual pattern of practice, local practice protocols, and fear of litigation, in addition to other potentially perverse factors such as financial incentives.

Not only were physicians’ risk estimates inaccurate but also they were not effectively communicated to their patients. Risk communication in a busy emergency department (ED) setting to patients with various levels of health literacy and education who may have a different cultural and ethnic background than their provider is far from straightforward. Both physicians and patients may have difficulty understanding and using numeric information, leading to what has been referred to as “collective statistical illiteracy.”6 Furthermore, in part because of patients’ difficulty with health literacy and numeracy, physicians often resort to using verbal qualifiers when communicating risk (eg, your future risk of heart attack is “low”), and studies have shown that interpretation of these imprecise terms is highly variable.7 For example, low risk to a physician might mean less than 5%, whereas to a patient it might mean less than 25%. Though beyond the scope of this editorial to describe in detail, there are several evidence-based approaches for risk communication of health information, such as use of absolute rather than relative risks, diagrams and pictographs to communicate risk and benefit information, and a consistent denominator when comparing risk and benefits of alternative management strategies, among others.8

Risk communication is a key element of shared decisionmaking, a collaborative process in which patients and providers make health care decisions together, taking into account the best scientific evidence available, as well as the patient’s values and preferences.9 To facilitate shared decisionmaking for patients with possible acute coronary syndrome, Newman et al1 suggests that calibration of physician risk to improve accuracy is a key component. Developing approaches that facilitate accurate risk communication and comprehension and allaying patient anxiety before engaging them in the decisionmaking process are also critical.

Decision aids, interventions or tools that facilitate shared decisionmaking and patient engagement in health care decisions have been developed for a number of medical conditions and decisions, some of which are frequently encountered in the ED setting.10-12 They have been shown to increase patient knowledge, increase the accuracy of risk perception, and decrease patients’ uncertainty related to feeling uninformed.13 Standards for decision aid design have been developed in an effort to overcome several of the challenges pointed out by the current investigation,14 including physician comprehension of risk, risk communication using evidence-based approaches, and transparent communication of the risks and benefits of alternative management strategies to patients. Additional work is needed to determine which decisions in the ED setting are appropriate for shared decisionmaking, to prioritize these conditions according to their potential effect, and to develop and test contextually sensitive approaches to risk communication.

3. Outcomes in presyncope patients: a prospective cohort study.

Thiruganasambandamoorthy V, et al. Ann Emerg Med. 2015;65(3):268-276.e6

Serious adverse events were noted in 5% of all patients presenting to the ED with presyncope and in 2% of those discharged to home.

STUDY OBJECTIVE: Presyncope is the sudden onset of a sense of impending loss of consciousness without losing consciousness (which differentiates it from syncope). Our goals are to determine the frequency of emergency department (ED) presyncope visits, management, 30-day outcomes, and emergency physicians' outcome prediction.

METHODS: Our prospective study at 2 academic EDs included adults with presyncope and excluded patients with syncope, mental status changes, seizure, and significant trauma. We collected patient characteristics, ED management, cause (vasovagal, orthostatic, cardiac, or unknown) at the end of the ED visit, and 30-day outcomes. Serious outcomes included death, arrhythmia, myocardial infarction, structural heart disease, pulmonary embolism, and hemorrhage. We also collected physicians' confidence in assigning the cause and their prediction probability for 30-day serious outcomes.

RESULTS: Presyncope constituted 0.5% of ED visits. We enrolled 881 patients: mean age 55.5 years, 55.9% women, and 4.7% hospitalized. Among 780 patients with 30-day follow-up, 40 (5.1%) experienced serious outcomes: death 0.3%, cardiovascular 3.1%, and noncardiac 1.8%. Of the 840 patients discharged home, 740 had follow-up data and 14 patients (1.9%) experienced serious outcomes after ED disposition. The area under the receiver operating characteristic curve for physician prediction probability was 0.58 (95% confidence interval 0.38 to 0.78). The incidence of serious outcomes was similar, whereas physician diagnostic confidence and prediction probability varied among the 4 causal groups.

CONCLUSION: Presyncope can be caused by serious underlying conditions. Emergency physicians had difficulty predicting patients at risk for serious outcomes after ED discharge. Future studies are needed to identify risk factors for serious outcomes after ED disposition.

4. Endovascular Therapy for Ischemic Stroke Finally Looks Good  

A. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection.

Campbell BC, et al; EXTEND-IA Investigators. N Engl J Med. 2015 Mar 12;372(11):1009-1018.

Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes.

We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days.

The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P less than 0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.

In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome.

B. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke.

Goyal M, et al. N Engl J Med. 2015 Mar 12;372(11):1019-1030.

Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation.

We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis).

The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P less than 0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P less than 0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75).

Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality.

C. Christmas Comes Early for Endovascular Therapy in Stroke

Radecki R. EM Lit of Note. Posted February 12, 2015

The key take-home, however, is endovascular therapy for acute stroke has probably finally arrived.  After a decade-and-a-half of generally failed trials, it seems the devices and patient selection have finally improved to the point of clinical utility.  For patients with collateral flow and one of these accessible lesions, it seems clear this therapy should be provided – and neither time of onset or tPA use matter as much as viable brain tissue.  But the obvious key, as shown in MR-CLEAN, is patient selection – ESCAPE only managed to enroll 1.4 patients per month per center, while EXTEND-IA screened 7,798 stroke patients over two years to come up with 70.  This therapy is very much so not for everyone – though, no doubt, Covidien hopes it will become so beyond the eligibility population identified here.

But, for the first time ever, if I were to have one of these specific types of heavily disabling strokes, this is probably the first advanced stroke intervention I'd willingly choose.

5. Better performance on length-of-stay benchmarks associated with reduced risk following ED discharge: an observational cohort study

Schull M, et al. CJEM 2015 Feb 09 [Epub ahead of print]

Introduction Emergency department (ED) crowding is associated with adverse outcomes. Several jurisdictions have established benchmarks and targets for length-of-stay (LOS) to reduce crowding. An evaluation has been conducted on whether performance on Ontario’s ED LOS benchmarks is associated with reduced risk of death or hospitalization.

Methods A retrospective cohort study of discharged ED patients was conducted using population-based administrative data from Ontario (April 2008 to February 2012). For each ED visit, the proportion of patients seen during the same shift that met ED LOS benchmarks was determined. Performance was categorized as less than 80%, 80% to 90%, 90% to 95%, and 95%–100% of same-shift ED patients meeting the benchmark. Logistic regression models analysed the association between performance on ED LOS benchmarks and 7-day death or hospitalization, controlled for patient and ED characteristics and stratified by patient acuity.

Results From 122 EDs, 2,295,256 high-acuity and 1,626,629 low-acuity visits resulting in discharge were included. Deaths and hospitalizations within 7 days totalled 1,429 (0.062%) and 49,771 (2.2%) among high-acuity, and 220 (0.014%) and 9,005 (0.55%) among low-acuity patients, respectively. Adverse outcomes generally increased among patients seen during shifts when a lower proportion of ED patients met ED LOS benchmarks. The adjusted odds ratios (and 95% confidence intervals) among high- and low-acuity patients seen on shifts when less than 80% met ED benchmarks (compared with ≥95%) were, respectively, 1.32 (1.05–1.67) and 1.84 (1.21–2.81) for death, and 1.13 (1.08–1.17) and 1.40 (1.31–1.49) for hospitalization.

Conclusions Better performance on Ontario’s ED LOS benchmarks for each shift is associated with a 10%–45% relative reduction in the odds of death or admission 7 days after ED discharge.

Full-text (free):  Then select pdf or HTML for full-text.

6. The Use of Subdissociative-dose Ketamine for Acute Pain in the ED.

Sin B, et al. Acad Emerg Med. 2015 Mar;22(3):251-7.

OBJECTIVES: Ketamine is a well-known anesthetic with its use trailing back to the 1960s. It has antagonistic effects at the N-methyl-d-aspartate receptor. There is emerging literature to suggest the use of subdissociative-dose ketamine (SDDK) for pain reduction. This evidence-based review evaluates the evidence regarding the use of SDDK for acute pain control in the emergency department (ED).

METHODS: The MEDLINE and EMBASE databases were searched. Randomized controlled trials (RCTs) that described or evaluated the use of SDDK for acute pain in the ED were included. Literature was excluded if it was not published in English. Duplicate articles, unpublished reports, abstracts, and review articles were also excluded. Quality assessment and evaluation of literature were evaluated based on the GRADE criteria. The primary outcome of interest in this review was the difference in pain score from baseline to cutoff time as specified in the studies. Secondary outcome measures were the incidence of adverse events and reduction in the amount of adjuvant opioids consumed by patients who received SDDK.

RESULTS: Four RCTs met the inclusion criteria, which enrolled a total of 428 patients. Three adult trials and one pediatric trial were identified. The level of evidence for the individual trials ranged from low to moderate. A significant reduction in pain scores was only found in two of the four trials. One trial found a significant reduction in mean pain scores when ketamine was compared to morphine (p less than 0.05). Another trial reported a significant decrease in mean distress scores, favoring SDDK over fentanyl (1.0 vs. 2.7, p less than 0.05). One trial found a significant reduction in the amount of morphine consumed, favoring ketamine over placebo (0.14 mg/kg, 95% confidence interval [CI] = 0.13 to 0.16 mg/kg vs. 0.2 mg/kg, 95% CI = 0.18 to 0.22 mg/kg; p less than 0.001). An emergence phenomenon was reported in one trial.

CONCLUSIONS: Four RCTs with methodologic limitations failed to provide convincing evidence to either support or refute the use of SDDK for acute pain control in the ED.

7. Changes in ED Use among Young Adults after the Patient Protection and Affordable Care Act’s Dependent Coverage Provision

Antwi YA, et al. Ann Emerg Med. 2015 Mar 10 [Epub ahead of print]

Study objective
Since September 2010, the Patient Protection and Affordable Care Act has allowed young adults to remain as dependents on their parents’ private health plans until age 26 years. This insurance expansion could improve the efficiency of medical care delivery by reducing unnecessary emergency department (ED) use. We evaluated the effect of this provision on ED use among young adults.

We used a nationally representative ED visit database of more than 17 million visits from 2007 to 2011. Our analysis compared young adults aged 19 to 25 years (the age group targeted by the law) with slightly older adults aged 27 to 29 years (control group), before and after the implementation of the law.

The quarterly ED-visit rate decreased by 1.6 per 1,000 population (95% confidence interval 1.2 to 2.1) among targeted young adults after the implementation of the provision, relative to a comparison group. The decrease was concentrated among women, weekday visits, nonurgent conditions, and conditions that can be treated in other settings. We found no effect among weekend visits or visits due to injuries or urgent conditions. The provision also changed the health insurance composition of ED visits; the fraction of privately insured young adults increased, whereas the fraction of those insured through Medicaid and those uninsured decreased.

The Patient Protection and Affordable Care Act dependent coverage expansion was associated with a statistically significant yet modest decrease in ED use, concentrated in the types of ED visits that were likely to be responsive to changes to insurance status. In response to the law, young adults appeared to have altered their visit pattern to reflect a more efficient use of medical care.

8. Comparative effectiveness of diagnostic testing strategies in ED patients with CP: an analysis of downstream testing, interventions, and outcomes.

Foy AJ, et al. JAMA Intern Med. 2015 Mar 1;175(3):428-36.

IMPORTANCE: Patients presenting to the emergency department (ED) with chest pain whose evaluation for ischemia demonstrates no abnormalities receive further functional or anatomical studies for coronary artery disease; however, comparative evidence for the various strategies is lacking and multiple testing options exist.

OBJECTIVE: To compare chest pain evaluation pathways based on their association with downstream testing, interventions, and outcomes for patients in EDs.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of health insurance claims data for a national sample of privately insured patients from January 1 to December 31, 2011. Individuals with a primary or secondary diagnosis of chest pain in the ED were selected and classified into 1 of 5 testing strategies: no noninvasive testing, exercise electrocardiography, stress echocardiography, myocardial perfusion scintigraphy, or coronary computed tomography angiography.

MAIN OUTCOMES AND MEASURES: The proportion of patients in each group who received a cardiac catheterization, coronary revascularization procedure, or future noninvasive test as well as those who were hospitalized for an acute myocardial infarction (MI) during 7 and 190 days of follow-up.

RESULTS: In 2011, there were 693 212 ED visits with a primary or secondary diagnosis of chest pain, accounting for 9.2% of all ED encounters. After application of the inclusion and exclusion criteria, 421 774 patients were included in the final analysis; 293 788 individuals did not receive an initial noninvasive test and 127 986 did, representing 1.7% of all ED encounters. Overall, the percentage of patients hospitalized with an MI was very low during both 7 and 190 days of follow-up (0.11% and 0.33%, respectively). Patients who did not undergo initial noninvasive testing were no more likely to experience an MI than were those who did receive testing. Compared with no testing, exercise electrocardiography, myocardial perfusion scintigraphy, and coronary computed tomography angiography were associated with significantly higher odds of cardiac catheterization and revascularization procedures without a concomitant improvement in the odds of experiencing an MI.

CONCLUSIONS AND RELEVANCE: Patients with chest pain evaluated in the ED who do not have an MI are at very low risk of experiencing an MI during short- and longer-term follow-up in a cohort of privately insured patients. This low risk does not appear to be affected by the initial testing strategy. Deferral of early noninvasive testing appears to be reasonable.

Here’s the opener of the related editorial:
Stress Testing in the ED: Not Which Test but Whether Any Test Should Be Done

Redberg RF. JAMA Intern Med. 2015;175(3):436.

Chest pain is one of the most challenging symptoms for emergency medicine physicians to evaluate. They must identify patients with cardiac ischemia without subjecting all patients, the overwhelming majority of whom do not have ischemia, to unnecessary testing. Most patients evaluated in the emergency department (ED) for chest pain who have normal electrocardiogram findings and negative results of cardiac biomarker tests do not have cardiac ischemia. Thus, the question should not be what further testing to perform, but should any further testing be done in the ED…

9. Young Patients with Suspected Uncomplicated Renal Colic are Unlikely to Have Dangerous Alternative Diagnoses or Need Emergent Intervention

Schoenfeld EM, et al. West J Emerg Med 2015 Mar 13 [Epub ahead of print]

Introduction: In the United States there is debate regarding the appropriate first test for new-onset renal colic, with non-contrast helical computed tomography (CT) receiving the highest ratings from both Agency for Healthcare Research and Quality and the American Urological Association. This is based not only on its accuracy for the diagnosis of renal colic, but also its ability to diagnose other surgical emergencies, which have been thought to occur in 10-15% of patients with suspected renal colic, based on previous studies. In younger patients, it may be reasonable to attempt to avoid immediate CT scan if concern for dangerous alternative diagnosis is low, based on the risks of radiation from CT scans, and particularly in light of evidence that patients with renal colic have a very high likelihood of having multiple CT scans in their lifetimes. The objective is to determine the proportion of patients with a dangerous alternative diagnosis in adult patients age 50 and under presenting with uncomplicated (non-infected) suspected renal colic, and also to determine what proportion of these patients undergo emergent urologic intervention.

Methods: Retrospective chart review of 12 months of patients age 18-50 presenting with “flank pain,” excluding patients with end stage renal disease, urinary tract infection, pregnancy and trauma. Dangerous alternative diagnosis was determined by CT scan.

Results: Two hundred and ninety-one patients met inclusion criteria. One hundred and fifteen patients had renal protocol CT scans, and zero alternative emergent or urgent diagnoses were identified (one-sided 95% CI 0-2.7%). Of the 291 encounters, there were 7 urologic procedures performed upon first admission (2.4%, 95% CI [1.0-4.9%]). The prevalence of kidney stone by final diagnosis was 58.8%.

Conclusion: This small sample suggests that in younger patients with uncomplicated renal colic, the benefit of immediate CT scan for suspected renal colic should be questioned. Further studies are needed to determine which patients benefit from immediate CT scan for suspected renal colic, and which patients could undergo alternate imaging such as ultrasound.

10. Arterial puncture using insulin needle is less painful than with standard needle: a randomized crossover study.

Ibrahim I, et al. Acad Emerg Med. 2015 Mar;22(3):315-20.

OBJECTIVES: Arterial punctures are important procedures performed by emergency physicians in the assessment of ill patients. However, arterial punctures are painful and can create anxiety and needle phobia in patients. The pain score of radial arterial punctures were compared between the insulin needle and the standard 23-gauge hypodermic needle.

METHODS: In a randomized controlled crossover design, healthy volunteers were recruited to undergo bilateral radial arterial punctures. They were assigned to receive either the insulin or the standard needle as the first puncture, using blocked randomization. The primary outcome was the pain score measured on a 100-mm visual analogue scale (VAS) for pain, and secondary outcomes were rate of hemolysis, mean potassium values, and procedural complications immediately and 24 hours postprocedure.

RESULTS: Fifty healthy volunteers were included in the study. The mean (±standard deviation) VAS score in punctures with the insulin needle was lower than the standard needle (23 ± 22 mm vs. 39 ± 24 mm; mean difference = -15 mm; 95% confidence interval = -22 mm to -7 mm; p less than 0.001). The rates of hemolysis and mean potassium value were greater in samples obtained using the insulin needle compared to the standard needle (31.3% vs. 11.6%, p = 0.035; and 4.6 ±0.7 mmol/L vs. 4.2 ±0.5 mmol/L, p = 0.002). Procedural complications were lower in punctures with the insulin needle both immediately postprocedure (0% vs. 24%; p less than 0.001) and at 24 hours postprocedure (5.4% vs. 34.2%; p = 0.007).

CONCLUSIONS: Arterial punctures using insulin needles cause less pain and fewer procedural complications compared to standard needles. However, due to the higher rate of hemolysis, its use should be limited to conditions that do not require a concurrent potassium value in the same blood sample.

11. Images (and a Video) in Clinical Practice

Adult Intussusception
This report presents the case of a 37-year-old man with multiple Emergency Department visits for abdominal pain and with negative results for prior imaging studies, who was eventually diagnosed with intussusception after 5 years of recurrent symptoms. The case is followed by a review of the literature.

Cecal Diverticulitis

Descending Necrotizing Mediastinitis in an Infant

Acute PEG Tube Erosion

Penile Fracture

Passage of a Sialolith

Femoral-Head Dislocation to the Scrotum

Disseminated Zoster

Putting On and Removing Personal Protective Equipment

12. Targeted temperature management: It is not yet time to change your target temperature

Clinkarda D, et al. CJEM 2015 Feb 05 [Epub ahead of print]

Bottom Line: Based on previous RCTs showing survival benefit, a strong safety profile, and the failure of this study to show superiority, a change in the current target temperature aiming at 33°C (91.4°F) may not be warranted.

Background: Two randomized control trials (RCTs) suggested that targeted temperature management (TTM) (previously referred to as therapeutic hypothermia) to a target of 32°C–34°C (89.6°F–93.2°F) post-cardiac arrest is associated with improved mortality and neurologic function in ventricular fibrillation and ventricular tachycardia arrests.1,2 One trial failed to show the benefit from cooling patients presenting with pulseless electrical activity (PEA) and asystole.3 Both the 2009 and 2012 Cochrane Reviews concluded: “With conventional cooling methods... patients were 55% more likely to leave the hospital without major brain damage.”4 However, a meta-analysis by Nielson et al.5 (2012) described the overall quality of evidence as low and suggested that a large-scale clinical trial should be conducted. Nielson et al.5 hypothesized that the benefits demonstrated by TTM may come from the prevention of fever rather than from the induction of hypothermia.5 The reviewed study was designed to evaluate whether the degree of temperature reduction affects outcomes…

[Then follows a review of the design, methods, and results of Nielson N, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med 2013;369:2197-2206.]

This study addresses a contentious issue in post-resuscitative care of whether the benefits of current protocols are due to hypothermia or simply fever prevention. The trial included more TTM patients than all previous studies combined due to an impressive international collaboration.

This superiority trial was powered to detect an 11% absolute mortality difference between the 36°C (96.8°F) group and the 33°C (91.4°F) group (a relative risk reduction of 20%). A negative superiority trial should not be interpreted as proof that no difference exists between interventions. For example, there may have been an absolute risk reduction of 5%, but this would not have been detected with the given sample size. An equivalence or noninferiority trial design is necessary to correctly conclude that 33°C (91.4°F) is not better than 36°C (96.8°F).6 Failure to demonstrate superiority is not the same as proving equivalence; therefore, the proper interpretation of this failed superiority trial would be that there was no benefit from raising the target temperature from 33°C (91.4°F) to 36°C (96.8°F). This finding may be the result of a number of design features that make the 33°C (91.4°F) and 36°C (96.8°F) groups appear similar, potentially minimizing the effect of temperature on the primary outcome.

[Then follows a critique of the patient population and treatment.]

Despite the impressive trial size and other aforementioned strengths, clinicians should be cautious about changing their practices from the current American Heart Association guidelines of cooling to 32°C–34°C (89.6°F–93.2°F).8 There are now two positive and two negative trials on the survival benefit of TTM post-cardiac arrest, each with methodologic differences.1,2,4,9 Both negative trials included PEA and asystolic arrests, whereas both positive trials excluded them. This study does suggest important clinical concepts that deserve further investigation, in particular, the optimal temperature of therapeutic hypothermia and the acceptable delay in achieving the target temperature.

Full-text (free): Then select pdf or HTML for the full-text.

13. Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease

Douglas PS, et al. New Engl J Med 2015 Mar 14 [Epub ahead of print]

Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care.

We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure.

The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P=0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P less than 0.001).

In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years.

14. Comparison of long-term neurological outcomes in adults with traumatic ICH admitted to the ICU versus the floor

Nishijima DK, et al. West J Emerg Med 2015 March 2 [Epub ahead of print]

The objective of this study was to compare long-term neurological outcomes in low-risk patients with traumatic intracranial hemorrhage (tICH) admitted to the ICU versus patients admitted to the floor.

Methods This retrospective study was conducted at a Level 1 trauma center from October 1, 2008 to February 1, 2013. We defined low-risk patients as: age less than 65 years, isolated head injury, normal admission mental status, and no shift or swelling on initial head CT. Clinical data were abstracted from a trauma registry and linked to a brain injury database. Extended Glasgow Outcome Scale (GOS-E) score at six months was compared between patients admitted to the ICU and patients admitted to the floor. We did a risk-adjusted analysis of the influence of floor admission on a normal GOS-E.

One hundred fifty one patients were identified; 45 (30%) were admitted to the floor and 106 (70%) to the ICU. Twenty-three (51%; 95% CI 36-66%) patients admitted to the floor and 55 (52%; 95% CI 42-62%) patients admitted to the ICU had a normal GOS-E. On adjusted analysis, the odds ratio for floor admission was 0.77 (95% CI 0.36-1.64) for a normal GOS-E at six months.

Long-term neurological outcomes in low-risk patients with tICH were not markedly different between patients admitted to the ICU and those admitted to the floor. However, we were unable to demonstrate non-inferiority on adjusted analysis. Future work aimed at a larger, prospective cohort may better evaluate the relative impacts of admission type on outcomes.

15. Four-factor PCC vs plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial

Goldstein JN, et al. The Lancet 2015 February 26 [Epub ahead of print]

Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures.

In a multicentre, open-label, phase 3b randomised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure. We randomly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC (Beriplex/Kcentra/Confidex; CSL Behring, Marburg, Germany) or plasma, with dosing based on international normalised ratio (INR) and weight. The primary endpoint was effective haemostasis, and the co-primary endpoint was rapid INR reduction (≤1·3 at 0·5 h after infusion end). The analyses were intended to evaluate, in a hierarchical fashion, first non-inferiority (lower limit 95% CI greater than −10% for group difference) for both endpoints, then superiority (lower limit 95% CI above 0%) if non-inferiority was achieved. Adverse events and serious adverse events were reported to days 10 and 45, respectively. This trial is registered at, number NCT00803101.

181 patients were randomised (4F-PCC n=90; plasma n=91). The intention-to-treat efficacy population comprised 168 patients (4F-PCC, n=87; plasma, n=81). Effective haemostasis was achieved in 78 (90%) patients in the 4F-PCC group compared with 61 (75%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 14·3%, 95% CI 2·8–25·8). Rapid INR reduction was achieved in 48 (55%) patients in the 4F-PCC group compared with eight (10%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 45·3%, 95% CI 31·9–56·4). The safety profile of 4F-PCC was generally similar to that of plasma; 49 (56%) patients receiving 4F-PCC had adverse events compared with 53 (60%) patients receiving plasma. Adverse events of interest were thromboembolic adverse events (six [7%] patients receiving 4F-PCC vs seven [8%] patients receiving plasma), fluid overload or similar cardiac events (three [3%] patients vs 11 [13%] patients), and late bleeding events (three [3%] patients vs four [5%] patients).

4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures.

16. Trial of Early, Goal-Directed Resuscitation for Septic Shock

The Promise Study confirms what we learned from Process and Arise

Mouncey PR, et al. N Engl J Med. 2015 Mar 17. [Epub ahead of print]

Background Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains.

Methods We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days.

Results We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.

Conclusions In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome.

17. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections.

Miller LG, et al. N Engl J Med. 2015 Mar 19;372(12):1093-103.

BACKGROUND: Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.

METHODS: We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.

RESULTS: A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.

CONCLUSIONS: We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses.

18. The Screened & Examined Podcast Takes on Dr. Oz

In an earlier Lit Bits (Dec 27, 2014), we included this important article from the BMJ: Televised medical talk shows—what they recommend and the evidence to support their recommendations: a prospective observational study. Full-text:

Dustin Ballard, MD, MBE, emergency physician, clinical researcher, author, and co-chair of the KP CREST Network, explores this topic further on the opening session of his new podcast.

Ballard D. Emerg Med News. 2015;37(3A).

Podcasting is the new blogging — it's easy, virtually free, and anyone can do it. That does not mean, of course, that anyone will actually listen. Since I am as much of a sucker for a fad as the next guy, I have decided to join the podcasting movement. But I am also savvy enough to just go ahead and skip the part where no one listens. So while you can choose to listen [], this pod is going to print no matter what. Here goes....

DB: Welcome to The Medically Clear Podcast. You are fortunate enough to join us for our inaugural broadcast. And depending on how this goes, perhaps you will be joining us for our final one as well. I am Dustin Ballard, an emergency physician, writer, and researcher, and “it” is known quite simply as the Fabulous “Creature” of the Literature.
Each episode I will be asking the “Creature” to pick a notable recent addition to the literature, and then flush and suss it out for us. We'll get to our inaugural article in a moment, but first, Creature, can you tell us a little bit more about yourself and your prolific podcasting resume?

CREATURE: Well, thanks, Dustin. You are too kind. I must admit that today does represent a milestone in my podcasting career. It's, in fact, my very first podcast.

DB: Excellent and welcome to the world of podcasting. So Creature, our featured science this week is from the British Medical Journal (2014;349:g7346), and addresses how medical television media packages evidence for health consumers. OK, let's start our Knowledge Translate segment and ask you to drop a Synopsis Bomb regarding this study.

CREATURE: A synopsis bomb? That sounds explosive. How about instead I just skim the paper and point out any methodological land mines I come across?

DB: That'll do…

19. Harms of CT scanning prior to surgery for suspected appendicitis

Rogers W, et al. Evid Based Med 2015;20:3-4  

Abdominal pain in young adults is a common symptom in the emergency department (ED) and most young patients who require surgery are suffering from appendicitis. Ten years ago patients suspected of having appendicitis went to surgery without any sort of imaging; today however CT scanning has become a reflexive part of the workup of young people with suspected appendicitis. In this commentary, we raise concerns about the harm/benefit ratio of routinely performing an abdominal CT scan on an otherwise healthy patient who presents to the ED with lower abdominal pain suggestive of appendicitis. We use published data to compare the long-term mortality risks from abdominal CT scanning in individuals younger than 50 with the mortality risks associated with an appendectomy that removes a normal appendix (a ‘negative’ appendectomy).

Morbidity and mortality risks of negative appendectomy
Although it is commonly assumed that there are significant risks associated with a negative appendectomy, the actual risk is negligible. The safety of negative appendectomy is evident in data describing surgical mortality from the UK National Health Service (NHS) laparoscopic appendectomy study, in which there were no deaths in 234 402 patients below the age of 49 who underwent that surgery.1 Appendectomies are associated with a 2–5% incidence of postoperative intra-abdominal wound infections.2 The risk of infection after a negative appendectomy is probably much lower since the resected appendix is not infected but the incidence of deep infection in these cases has not been studied. The other major morbidity of appendectomy is small bowel obstruction which occurs in less than 1% of cases. The advent of newer, less invasive surgical techniques and the broad range of anaesthesia safety initiatives have dramatically decreased the mortality and morbidity associated with appendectomy.

Morbidity and mortality risks of abdominal CT scan
Abdominal CT scanning is not without risks. The Board on Radiation Effect Research is sponsored by the National Research Council of the National Academies of Sciences. This board has studied data describing populations exposed to medical, environmental and occupational radiation as well as those exposed to radiation from the two atomic bomb explosions in Japan at the end of WW II. Based on this long term, large scale follow-up data the board has concluded that a 45-year-old patient exposed to 15 mSv of radiation experiences a 1:1250 additional risk for future mortality from cancer.3 Though the radiation dosage of CT scans varies, the average effective radiation dose of a single abdominal CT scan is 8–11 mSv.4

Of note, this risk statistic does not account for the increased risk of developing non-fatal cancer. Furthermore the risk of later cancer is much higher for younger patients. Acute appendicitis occurs most frequently in patients aged 10–19 years old,5 a group which is 10 times more sensitive to risk from radiation when compared to adults.6 An Israeli study investigating the relationship between CT scans in patients under the age of 18 and future cancer mortality risk concluded that CT scans alone performed on the paediatric population will cause a 0.29% increase in baseline future cancer mortality.7

Harms of CT scans are not limited to the increased future cancer mortality risk. Other potential harms include contrast dye-induced nephropathy and hypersensitivity reactions. Contrast dye-induced nephropathy, defined as a greater than 25% increase in serum creatinine levels after contrast administrations, occurs in 11% of patients undergoing CT scans. Renal failure occurs in 1% of those patients, 0.7% of those who develop renal failure die as a result.8

Estimating the risks and benefits of routine CT scanning for suspected appendicitis in young people
Extrapolation of data from a recent retrospective study of CT scanning and negative appendectomy9 rates allow us to estimate the risks and benefit of routine CT imaging of young patients with suspected appendicitis. At the institution studied in the article 2000 abdominal CT scans lead to 58 appendectomies. The Biological Effects of Ionizing Radiations (BEIR V) exposure data predict that 2000 CT scans would lead to at least one cancer death. Before CT scanning began at this institution approximately 23% of appendectomies showed no evidence of appendicitis, now the preoperative scan rate is 97.5% and as a result only 1.7% of appendectomies show no evidence of appendicitis. The benefit therefore of universal scanning was to avoid 12 negative appendectomies, this at the cost of one radiation-induced cancer death. One cancer death from imaging to prevent no surgical deaths from negative appendectomy is a trade-off that should lead us to question reflexive CT scanning of patients we suspect of having appendicitis.

It is unfortunate that there are no randomised trials comparing the management of suspected appendicitis with and without CT scanning. As CT scanners capable of imaging the abdomen became more available, their use in the evaluation of patients with abdominal pain grew rapidly and the advantages of increased diagnostic precision were far more evident than the risks. It is clear that from a diagnostic perspective the 98.3% specificity of CT scanning is far better than the 77% specificity achieved by clinician based purely on clinical judgment.9 A randomised study to compare risks and benefits of CT scanning versus clinical judgment would only be instructive if it followed patient outcomes for decades to make sure that the long-term complications of radiation exposure were accurately assessed.

The best diagnosticians among us rely on a detailed history, a careful examination, judicious use of testing and imaging and an intuition which can only be gained by experience. Unfortunately this approach to diagnosis has been supplanted by a blind faith in technology and a belief that an incorrect diagnosis represents a failure on the part of the clinician that could have been avoided if only a few more tests had been run. This reliance on testing and quest for perfection represents a new risk to patients. The principle stated in the Hippocratic oath, to do no harm, suggests that we should avoid routine CT scanning for likely cases of appendicitis in youth.

References (and full-text, free):

20. Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis

Rambaud-Althaus C, et al. Lancet 2015 Mar 10 [Epub ahead of print]

Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia.

We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged less than 5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis.

We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26–0·89; specificity 0·59, 0·29–0·84) and lower chest wall indrawing (four studies; 0·48, 0·16–0·82; 0·72, 0·47–0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45–2·48), grunting (1·78, 1·10–2·88), chest indrawing (1·76, 0·86–3·58), and nasal flaring (1·75, 1·20–2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09–0·96), history of fever (0·53, 0·41–0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23–0·83).

Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy.

21. Cervical Spine Clearance in Obtunded Patients after Blunt Traumatic Injury: A Systematic Review

Badhiwala JH, et al. Ann Intern Med.  2015;162(6):429-437.

Background: Cervical spine clearance protocols are controversial for unconscious patients after blunt traumatic injury and negative findings on computed tomography (CT).

Purpose: To review evidence about the utility of different cervical spine clearance protocols in excluding significant cervical spine injury after negative CT results in obtunded adults with blunt traumatic injury.

Data Sources: MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library were searched from January 2000 through November 2014.

Study Selection: English-language studies that examined patients with negative CT results having confirmatory routine testing with magnetic resonance imaging (MRI), dynamic radiography, or clinical examination and that reported outcome measures of missed cervical spine injury, need for operative stabilization, or prolonged use of cervical collars.

Data Extraction: Independent reviewers evaluated the quality of studies and abstracted the data according to a predefined protocol.

Data Synthesis: Of 28 observational studies (3627 patients) that met eligibility criteria, 7 were prospective studies (1686 patients) with low risk of bias and well-interpreted, high-quality CT scans. These 7 studies showed that 0% of significant injuries were missed after negative CT results. The overall studies using confirmatory routine testing with MRI showed incidence rates of 0% to 1.5% for cervical spine instability (16 studies; 1799 patients), 0% to 7.3% for need for operative fixation (17 studies; 1555 patients), and 0% to 29.5% for prolonged collar use (16 studies; 1453 patients).

Limitations: Most studies were retrospective. Approaches to management of soft tissue changes with collars varied markedly.

Conclusion: Cervical spine clearance in obtunded adults after blunt traumatic injury with negative results from a well-interpreted, high-quality CT scan is probably a safe and efficient practice.

22. Investigating and managing suspected PE in an outpatient [clinic!] setting: the Leicester experience

Vali Y, et al. Thorax. 2015 Mar;70(3):291-3..

Having established an ambulatory service for patients with suspected and proven PE, we reviewed our outcomes. All patients referred from June 2010 to May 2012 were analysed. Of 971 patients referred, 905 underwent complete assessment (66 admitted as ineligible). 754 (77.7%) patients were discharged and required no follow-up. 96 (10.6%) patients had PE confirmed of whom 70 (72.9%) were managed as outpatients. 14 (1.6%) patients have died since attending the clinic; no death was related to PE. This audit shows that ambulatory investigation and management of selected low risk patients with suspected PE is safe and reduces hospital admissions.

23. Micro Bits

A. Iodinated Contrast Prior to Thrombolysis Was Not Associated With Worse Intracranial Hemorrhage

B. Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

Kids can't take peanut butter to school. Some airlines no longer serve peanuts because of fear of anaphylaxis among passengers. These developments are just the tip of the iceberg as the prevalence of peanut allergy among children continues to increase worldwide, especially in westernized countries. In the United States alone, the prevalence has more than quadrupled in the past 13 years, growing from 0.4% in 1997 to 1.4% in 20081 to more than 2% in 2010.2 Peanut allergy has become the leading cause of anaphylaxis and death related to food allergy in the United States.3

C. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial

D. Improving patient knowledge and safe use of opioids: a randomized controlled trial.

E. Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial.

F. Ambulatory vital signs in the workup of pulmonary embolism using a standardized 3-minute walk test

G. Cardiac Screening With Electrocardiography, Stress Echocardiography, or Myocardial Perfusion Imaging: Advice for High-Value Care From the American College of Physicians

H. AMI: What’s in a name?

Type 1 and Type 2 MIs

I. ADHD medications are misused by 1 in 6 college students

Seventeen percent of college students have used stimulants prescribed to treat attention-deficit/hyperactivity disorder without a prescription or taken bigger doses than prescribed, according to a meta-analysis published in Clinical Child and Family Psychology Review. Students often got the medications from their friends.

J. Viruses account for majority of childhood pneumonia cases in U.S.

A study in the New England Journal of Medicine revealed 66% of pneumonia cases in more than 2,000 children were associated with viral infections, while 8% were linked to bacterial infection and 7% were tied to both. Researchers also found patients younger than 2 years were at higher risk of the lung infection, with cases reaching up to 62 per 10,000 children annually.

K. Music as Medicine

Music is important for many physicians -- but can doctors use music to promote the health and well-being of their patients? A variety of studies suggest the answer may be yes. Some are blinded, randomized trials, but most are relatively small and brief. Still, they present an interesting group of observations.