Lit Bits: May 22, 2016

From the recent medical literature...

1. The Opioid Epidemic: Trends, Regulations, and Alternatives

A. Opioid Prescriptions Drop for First Time in Two Decades

By ABBY GOODNOUGH and SABRINA TAVERNISE. New York Times. May 20, 2016

WASHINGTON — After years of relentless growth, the number of opioid prescriptions in the United States is finally falling, the first sustained drop since OxyContin hit the market in 1996.

For much of the past two decades, doctors were writing so many prescriptions for the powerful opioid painkillers that, in recent years, there have been enough for every American adult to have a bottle. But for each of the past three years — 2013, 2014 and 2015 — prescriptions have declined, a review of several sources of data shows.

Experts say the drop is an important early signal that the long-running prescription opioid epidemic may be peaking, that doctors have begun heeding a drumbeat of warnings about the highly addictive nature of the drugs and that federal and state efforts to curb them are having an effect.

“The culture is changing,” said Dr. Bruce Psaty, a researcher at the University of Washington in Seattle who studies drug safety. “We are on the downside of a curve with opioid prescribing now.”

IMS Health, an information firm whose data on prescribing is used throughout the health care industry, found a 12 percent decline in opioid prescriptions nationally since a peak in 2012. Another data company, Symphony Health Solutions, reported a drop of about 18 percent during those years. Opioid prescriptions have fallen in 49 states since 2013, according to IMS, with some of the sharpest decreases coming in West Virginia, the state considered the center of the opioid epidemic, and in Texas and Oklahoma. (Only South Dakota showed an increase.)

So far, fewer prescriptions have not led to fewer deaths: fatal overdoses from opioids have continued to rise, taking more than 28,000 lives in 2014, according to the most recent federal health data. That number includes deaths from both prescription painkillers, like Percocet, Vicodin and OxyContin, and heroin, an illegal opioid whose use has been rising as access to prescription drugs has tightened.

While experts agree that the decline is real, they differ on what it means for patients. Some say opioid prescribing has been too loose for too long, and that it must be tightened, even if that means extra hurdles for patients in pain.

“The urgency of the epidemic, its devastating consequences, demands interventions that in some instances may make it harder for some patients to get their medication,” said Dr. Nora Volkow, the director of the National Institute on Drug Abuse. “We need to set up a system to make sure they are covered. But we cannot continue the prescription practice of opioids the way we have been. We just can’t.”

Others argue that efforts to rein in prescribing have gone too far and are penalizing patients who take the medicines responsibly and need them for relief.

“The climate has definitely shifted,” said Dr. Daniel B. Carr, the director of Tufts Medical School’s program on pain research education and policy. “It is now one of reluctance, fear of consequences and encumbrance with administrative hurdles. A lot of patients who are appropriate candidates for opioids have been caught up in that response.”

Opioid painkillers present a uniquely difficult public policy puzzle, in part because they became so essential to so many Americans and health officials remained deadlocked for years over how to handle them.

In the past, prescribing of opioids was limited, often aimed at the pain that comes after surgery or with terminal illnesses like cancer. But it took off in the 1990s, as drug companies and medical experts argued that opioids could be used to treat chronic conditions like back pain without addicting patients. Medical residents began learning that pain was the “fifth vital sign” — a body function to be assessed after temperature, heart rate, respiration rate and blood pressure — and that opioids could help mitigate it safely. Sales of the drugs exploded, rising to nearly $10 billion in 2015, from $1 billion in 1992, according to IMS.

But recently, some doctors say they have detected a shift in the attitudes of some patients toward opioids.

“It used to be that people would come in and sometimes be quite insistent” about receiving opioids, said Dr. Wanda Filer, the president of the American Academy of Family Physicians. But in the past year or two, she said, “I think we’ve seen some dampening of that effect. It’s all anecdotal, but I’m hearing it state by state, all around.”

Nationally, some of the biggest declines have been in the prescribing of hydrocodone, according to IMS and Symphony Health. These drugs, which include brands like Vicodin and Lortab, remain the most broadly prescribed opioids, often given after routine dental work or other minor procedures. Prescriptions for OxyContin declined, but those for generic oxycodone went up, IMS data showed. The data measures numbers of prescriptions, not pills, but is a rough proxy for Americans’ use of opioids….

The remainder of the essay: http://www.nytimes.com/2016/05/21/health/opioid-prescriptions-drop-for-first-time-in-two-decades.html

B. Limiting the Duration of Opioid Prescriptions: Balancing Excessive Prescribing and the Effective Treatment of Pain

Bateman BT, et al. JAMA Intern Med. 2016;176(5):583-584.

Prescription opioid misuse is a major public health issue in the United States. Since the late 1990s, sales of prescription opioids have risen 4-fold, and the rates of admissions for substance use treatment and of death from opioid overdose have grown proportionately.1 In response, training programs about the appropriate prescribing of opioid therapy have been developed, prescription monitoring programs implemented, and access to naloxone facilitated to reduce deaths among people who overdose. In general, these strategies focus on detecting and preventing harm in those who are already dependent on or misusing opioids. Although the impact of many of these programs is uncertain, the opioid epidemic continues to grow.

A more radical policy approach is to restrict the amount of opioids in first-time prescriptions to just a few days’ supply, perhaps 3 to 7 days. Recently, this strategy attracted much attention as a central component of legislation from the Governor of Massachusetts, Charlie Baker, which he signed into law on March 14, 2016.2 As part of a package of related interventions, the new Massachusetts law limits first-time prescriptions for opioids to 7 days, with specific exceptions, such as prescriptions for cancer pain or palliative care. In New York City, many hospital emergency departments have adopted voluntary guidelines that call for practitioners to prescribe no more than 3 days’ supply of short-acting opioids. Other states have imposed limits on the supply and dose of prescribed opioids, although these are not nearly as restrictive as the limits being implemented in Massachusetts.3

Mandated limits on opioid prescriptions for acute pain could promote safer use. First, it would reduce the exposure of first-time users to these addictive substances following episodes of acute pain. For some patients who come to misuse opioids, their euphoria or sedating effects are initially experienced in the context of routine medical care. There are countless anecdotes of patients who take opioids for a minor orthopedic injury or some other acute pain condition and then go on to use prescription opioids nonmedically. A recent population-based study suggested that 6% of incident opioid users progress to long-term use.4 Another study found that patients who received opioids following minor surgery were 44% more likely to become long-term opioid users compared to those who did not.5 Decreasing the initial amount dispensed may lessen the risk that patients develop an affinity for these drugs and transition to chronic use or misuse.

Second, mandated limits would more clearly align the amount of opioid prescribed with the amount actually needed and thereby substantially reduce the amount of unused opioid medication introduced into the community. Physicians often write prescriptions for opioids that are greatly in excess of what patients actually take for acute pain, and patients often keep the leftover medication. For example, a survey of adults in Utah estimated that in the previous 12 months, 1 in 5 state residents were prescribed an opioid medication.6 Of those who filled a prescription for an opioid, 72% had leftover pills and nearly three-quarters of those with leftover pills kept them. This equates to approximately 10% of the adult population of Utah who held on to leftover opioids over just a 1-year period. Leftover medications are an important source of opioids that are misused or diverted.7

Restricting the amount of opioids that can be prescribed will not address all of the contributing factors to the opioid epidemic, such as misuse or diversion among patient who are already chronically using opioids. It is also uncertain how many pills patients need to take to initiate an opioid use disorder. Perhaps clinicians should rethink the indications for opioids in any quantity, and reserve the medications for only truly severe pain.

Legislating limits on opioid prescriptions would create important challenges…

The remainder of the essay: http://archinte.jamanetwork.com/article.aspx?articleid=2511328

C. As Opioid Prescribing Guidelines Tighten, Mindfulness Meditation Holds Promise for Pain Relief

Jacob JA. JAMA. 2016 May 20 [Epub ahead of print]

Try nonpharmacologic and nonopioid therapies first, the Centers for Disease Control and Prevention (CDC) recommended in a recently published opioid prescribing guideline for primary care clinicians in outpatient settings (Dowell D et al. JAMA. 2016;315[15]:1624-1645). The CDC’s call for nonpharmacologic approaches may serve to heighten clinician interest in nonpharmacologic strategies for managing chronic pain, such as mindfulness-based stress reduction (MBSR), commented Steven Stanos, DO, medical director for the Swedish Pain Services at Swedish Medical Center in Seattle, and president-elect of the American Academy of Pain Medicine.

“Hopefully, the [CDC guideline] will be a good push to get physicians to start thinking about [behavioral-based pain management therapies] in primary care,” Stanos said.

In mindfulness meditation, a person is taught to become aware of his or her breathing, thoughts, and physical sensations in the present moment and view them without judgment (Tang YY and Leve LD. Transl Behav Med. 2016;6[1]:63-72). Limited research indicates that mindfulness meditation for pain management therapy has promise (Lee C et al. Pain Med. 2014;15:S21-39). However, pain management researchers note that research gaps need to be filled and better ways of referring patients to mindfulness meditation programs established before physicians can add the therapy to clinical practice.

“Learning for who and how [mindfulness] can work is at the very early stage,” said Josephine Briggs, MD, director of the National Institutes of Health’s National Center for Complementary and Integrative Health (NCCIH).

Recently, 2 large randomized trials showed that mindfulness meditation can help reduce chronic low back pain. Researchers at the Group Health Research Institute in Seattle randomized 342 adults with chronic lower back pain into 3 groups: 1 participated in 8 weekly 2-hour MBSR sessions that included meditation and yoga, another took part in 8 weekly 2-hour sessions using cognitive behavioral therapy (CBT) training to teach participants how to change their thoughts about pain, and a third was a usual care group (Cherkin DC et al. JAMA. 2016;315[12]:1240-1249). The MBSR and CBT groups also continued with their usual medical care, and participants received materials and instructions to practice between sessions. After 26 weeks, 43.6% of adults in the MBSR group had experienced clinically meaningful reduction in pain compared with 44.9% in the CBT group and 26.6% who received only usual care, which included anti-inflammatory medications, opioids, or physical therapy.

Another study involving 282 older adults at the University of Pittsburgh School of Medicine showed that mindfulness meditation could help reduce chronic low back pain. The intervention group was offered 8 weekly mindfulness meditation sessions, followed by 6 monthly sessions. At the 6-month mark, 44.4% of the intervention group experienced at least a 30% decrease in their current chronic low back pain compared with 25.2% of the control group (Morone NE et al. JAMA Intern Med. 2016;176[3]:329-337).

Such studies highlight how mind-body therapies like mindfulness meditation can be used to shift chronic pain treatment from a “biomedical disease model” to a “patient-centered” model focused on “patient engagement in daily self-management,” a recent JAMA editorial noted (Goyal M et al. JAMA. 2016;315[12]:1236-1237).

These studies and others also illustrate that pain is a complex phenomenon involving more than a direct nerve impulse from the affected tissue or limb to the somatic sensory cortex, Briggs explained. A person’s thoughts and emotions also play a role in pain perception, she said.

“That’s one of the reasons why there is growing recognition that learning strategies to diffuse or reduce the emotions associated with pain and the fear associated with pain may help give people a better sense of control [over their pain],” Briggs said.

Mindfulness meditation helps calm the fear that pain awakens, said Eric Schoomaker, MD, PhD, professor and vice chair for leadership, programs, and centers in the department of military and emergency medicine, Uniformed Services University of the Health Sciences in Bethesda, Maryland. Schoomaker also serves on the NCCIH advisory council.

“We catastrophize pain,” Schoomaker said. He explained that patients construct their own narratives of why they are in pain, how the pain felt in the past, and how it might feel in the future. Those thoughts can exacerbate sensations of pain, he noted. Mindfulness meditation helps patients, he added, by teaching patients how to observe their thoughts about pain without judgment or emotion…

The remainder of the essay (free): http://jama.jamanetwork.com/article.aspx?articleid=2524308

2. Misanalysis of Urinalysis: A Teachable Moment

Holroyd KB, et al. JAMA Intern Med. 2016;176(4):432-433.

A 64-year-old woman with a history of Bertolotti syndrome* causing chronic low back pain presented to the ED because she was experiencing medication withdrawal symptoms. She had recently stopped her home tramadol and tizanidine, no longer desiring to take any medications she viewed as habit forming. Within 24 hours of discontinuation, the patient developed cough, weakness, rhinorrhea, myalgias, and nausea—symptoms that had occurred for her in the past on stopping these medications. Notably, a review of her gastrointestinal symptoms was negative for any abdominal pain or diarrhea. On presentation she was hypertensive to 150/70 mm Hg and tachycardic to 115 beats per minute (bpm) but was afebrile. Findings from a complete physical examination and a chest radiograph were normal. Her laboratory test results were unremarkable, including a normal white blood cell (WBC) count. Although the patient did not complain of any urinary symptoms, a urinalysis was performed, which showed 4 epithelial cells per high-power field (hpf), 10 WBC/hpf, large leukocyte esterase, negative nitrites, and rare bacteria. She was prescribed a 7-day course of cefpodoxime, 100 mg twice a day, for a suspected urinary tract infection and discharged. Urine cultures were not ordered.

The patient’s initial presenting symptoms resolved; however, after 4 to 5 days she had an abrupt onset of watery diarrhea. The frequency of her bowel movements rapidly increased to 10 per day, in conjunction with the new onset of lower abdominal pain. Six days after her initial presentation, the patient developed a high fever (39.2°C) and again presented to the emergency department, where she remained febrile with a blood pressure of 105/71 mm Hg, heart rate of 128 bpm, and respiratory rate of 20 breaths per minute. Laboratory work revealed a new leukocytosis of 19.3 K/mm3. A repeated urinalysis once again showed pyuria and few bacteria. After fluid resuscitation and empirical parenteral antibiotics, the patient was admitted for treatment of sepsis, meeting the criteria of fever, heart rate, and leukocytosis. Owing to her recent antibiotic use, oral vancomycin was empirically started to treat Clostridium difficile colitis. The following day, stool polymerase chain reaction results were positive for C difficile toxin. Over the patient’s 4-day hospital stay the frequency of her diarrhea decreased, her fever and leukocytosis resolved, and she was discharged in stable condition and prescribed oral vancomycin.

This case exemplifies the consequences that can arise from antibiotic overuse in the setting of asymptomatic pyuria and misinterpretation of urinalyses. A recent study1 at the University of Toronto showed that 62% of patients admitted to the medicine service received a urinalysis despite 85% of these patients having no symptoms of a urinary tract infection (UTI). While a urinalysis is an inexpensive and quick way to evaluate for UTI, it still has many limitations. The presence of asymptomatic pyuria among healthy middle-aged women in the community is approximately 8.7%,2 and therefore urinalysis results must be interpreted in the context of the patient’s clinical presentation. Even in elderly populations, nonspecific symptoms are not to be used for diagnosis of UTI. Patients must still have burning pain, increased frequency, or increased urgency.3

Because our patient was not having any of these symptoms, her probability of having a UTI was very low. Thus, any diagnostic testing for UTI should not have affected treatment and should not have been performed.4 While there was no urine culture sent on the patient, a positive result would still not have warranted treatment. A Cochrane Review5 of 9 clinical trials examining treatment of asymptomatic bacteriuria concluded that treatment does not decrease the frequency of symptomatic infection yet significantly increases the number of adverse events, including diarrhea, rash, dizziness, candidiasis, swollen mouth, and vertigo. In addition, treatment may actually increase the risk of future symptomatic UTIs.

The patient in this case initially presented without urinary symptoms and was treated based on a single urinalysis mildly positive for WBCs and bacteria. Potentially as a result of this treatment, she returned with a severe C difficile infection, leading to a preventable illness and costly inpatient hospitalization. Neither treatment of nor screening for asymptomatic pyuria or bacteriuria is recommended in nonpregnant adults, with the exception of persistent catheter-acquired bacteriuria or patients undergoing urologic procedures involving mucosal bleeding or transurethral prostate resection. Heightened awareness of the diagnostic effectiveness of tests such as urinalysis and interpretation of results in the context of the patient’s pretest probability of disease would likely result in decreased iatrogenic adverse effects and more judicious use of health care resources.

References: http://archinte.jamanetwork.com/article.aspx?articleid=2498848

* Bertolotti syndrome: a total or partial unilateral or bilateral fusion of the transverse process of the lowest lumbar vertebra to the sacrum

3. Chewing Gum Test for Jaw Claudication in Giant-Cell Arteritis

Kuo C, et al. N Engl J Med 2016; 374:1794-1795.

Claudication of the jaw is a specific symptom with high predictive value for giant-cell arteritis.1 However, a standardized clinical test to differentiate claudication from other causes of jaw pain is lacking. We report two cases in which a “chewing gum test” for jaw claudication showed abnormal results.

In the first case, a woman, 61 years of age, who had received a clinical diagnosis of giant-cell arteritis 2 years earlier, presented with recurrence of pain in her right jaw, temporal headache, and lethargy after having been weaned from oral prednisolone therapy. The findings from a clinical examination were normal. She was asked to chew gum at the rate of one chew per second. After 2 minutes of chewing, she reported an ache in her right jaw that was similar to what she had felt 2 years earlier. The pain disappeared with rest but could be reproduced consistently after 2 to 3 minutes of chewing. The dose of her oral prednisolone therapy was increased, and her subjective symptoms resolved. The chewing gum test was repeated a few days later and showed normal results; no jaw ache was reported after 4 minutes of chewing.

In the second case, a woman, 77 years of age, presented with a 1-week history of vague temporal headache, blurred vision, and unsteady gait. Neuroimaging showed bilateral posterior circulation infarcts that involved the occipital lobes. She had an elevated erythrocyte sedimentation rate of 32 mm per hour, and her C-reactive protein level was 23 mg per liter. She reported no other symptoms of giant-cell arteritis, including claudication of the jaw. The findings from an ocular examination were normal. The temporal arteries were nontender and pulsatile. However, she reported an ache in her left jaw after 2 to 3 minutes of chewing gum at the rate of one chew per second. Findings from a biopsy of the temporal artery were consistent with a diagnosis of giant-cell arteritis (Figure 1).

On further questioning, the patient reported that her diet consisted mainly of soft-boiled vegetables. After prednisolone treatment, the patient reported no further jaw pain on the chewing gum test several months later.

Giant-cell arteritis is a potentially life-threatening and sight-threatening condition that remains difficult to diagnose and has no validated diagnostic criteria.2 Claudication of the jaw is reported in less than 50% of patients at presentation.1,3 Underreporting of jaw claudication may be a consequence of modern diets that require less mastication effort, particularly in the elderly population. The two cases reported here show that the chewing gum test (i.e., chewing gum at the rate of one chew per second) may be a simple and repeatable test for jaw claudication and allow for a better characterization of this symptom. In our patients, claudication of the jaw appeared after 2 to 3 minutes of chewing and resolved after prednisolone treatment. Further research is warranted to validate the chewing gum test for jaw claudication.

Image and references: http://www.nejm.org/doi/full/10.1056/NEJMc1511420

4. Pediatric Corner

A. Comparison of Prediction Rules and Clinician Suspicion for Identifying Children with Clinically Important Brain Injuries after Blunt Head Trauma.

Atabaki SM, et al. Acad Emerg Med. 2016 May;23(5):566-75.

OBJECTIVE: Children with minor head trauma frequently present to emergency departments (EDs). Identifying those with traumatic brain injuries (TBIs) can be difficult, and it is unknown whether clinical prediction rules outperform clinician suspicion. Our primary objective was to compare the test characteristics of the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules to clinician suspicion for identifying children with clinically important TBIs (ciTBIs) after minor blunt head trauma. Our secondary objective was to determine the reasons for obtaining computed tomography (CT) scans when clinical suspicion of ciTBI was low.

METHODS: This was a planned secondary analysis of a previously conducted observational cohort study conducted in PECARN to derive and validate clinical prediction rules for ciTBI among children with minor blunt head trauma in 25 PECARN EDs. Clinicians recorded their suspicion of ciTBI before CT as below 1, 1-5, 6-10, 11-50, or greater than 50%. We defined ciTBI as 1) death from TBI, 2) neurosurgery, 3) intubation for more than 24 hours for TBI, or 4) hospital admission of 2 nights or more associated with TBI on CT. To avoid overfitting of the prediction rules, we performed comparisons of the prediction rules and clinician suspicion on the validation group only. On the validation group, we compared the test accuracies of clinician suspicion greater than 1% versus having at least one predictor in the PECARN TBI age-specific prediction rules for identifying children with ciTBIs (one rule for children less than 2 years [preverbal], the other rule for children above 2 years [verbal]).

RESULTS: In the parent study, we enrolled 8,627 children to validate the prediction rules, after enrolling 33,785 children to derive the prediction rules. In the validation group, clinician suspicion of ciTBI was recorded in 8,496/8,627 (98.5%) patients, and 87 (1.0%) had ciTBIs. CT scans were obtained in 2,857 (33.6%) patients in the validation group for whom clinician suspicion of ciTBI was recorded, including 2,099/7,688 (27.3%) of those with clinician suspicion of ciTBI of less than 1% and 758/808 (93.8%) of those with clinician suspicion above 1%. The PECARN prediction rules were significantly more sensitive than clinician suspicion above 1% of ciTBI for preverbal (100% [95% confidence interval {CI} = 86.3% to 100%] vs. 60.0% [95% CI = 38.7% to 78.9%]) and verbal children (96.8% [95% CI = 88.8% to 99.6%] vs. 64.5% [95% CI = 51.3% to 76.3%]). Prediction rule specificity, however, was lower than clinician suspicion above 1% for preverbal children (53.6% [95% CI = 51.5% to 55.7%] vs. 92.4% [95% CI = 91.2% to 93.5%]) and verbal children (58.2% [95% CI = 56.9% to 59.4%] vs. 90.6% [95% CI = 89.8% to 91.3%]). Of the 7,688 patients in the validation group with clinician suspicion recorded as less than 1%, CTs were nevertheless obtained in 2,099 (27.3%). Three of 16 (18.8%) patients undergoing neurosurgery had clinician suspicion of ciTBI less than 1%.

CONCLUSIONS: The PECARN TBI prediction rules had substantially greater sensitivity, but lower specificity, than clinician suspicion of ciTBI for children with minor blunt head trauma. Because CT ordering did not follow clinician suspicion of less than 1%, these prediction rules can augment clinician judgment and help obviate CT ordering for children at very low risk of ciTBI.

Full-text (free): http://onlinelibrary.wiley.com/doi/10.1111/acem.12923/full

B. Half-strength apple juice can help some kids get through stomach flu

NEW YORK | BY WILL BOGGS MD (Reuters Health)

When little kids have the stomach flu and need to drink fluids, half-strength apple juice – and whatever fluid the child prefers - can be as effective as expensive electrolyte solutions, researchers say.

The treatment of stomach flu, or gastroenteritis, usually focuses on replacing fluids lost through diarrhea or vomiting, but the electrolyte solutions are relatively expensive and kids often don't like the way they taste.

“In many high-income countries, the use of dilute apple juice and preferred fluids may be an appropriate alternative to electrolyte maintenance solution use in children with mild gastroenteritis and minimal dehydration,” Dr. Steven D. Freedman from University of Calgary in Alberta, Canada told Reuters Health by email.

Freedman’s team studied 647 children ages six months to five years old who came to the emergency department with mild dehydration from stomach flu.

Half the children were given half-strength apple juice followed by their favorite drink, and half received an apple-flavored electrolyte solution, the researchers reported in the Journal of the American Medical Association.

Twenty-five percent of the kids who drank the electrolyte solution still needed intravenous (IV) fluids or other additional treatment, compared to only about 17 percent of the kids who drank apple juice and their favorite drink.

Two-year-olds and older children responded best to apple juice, but even the younger group fared slightly better with apple juice than with the electrolyte solution.

In addition, children treated with apple juice required fewer IV fluids and had lower hospitalization rates than children treated with the electrolyte solution.

"These results challenge the recommendation to routinely administer electrolyte maintenance solution when diarrhea begins," the researchers say.

But apple juice is not always the best treatment. “Our study specifically excluded high-risk children, and such children should continue to receive electrolyte maintenance solution,” Freedman said. “This would include children younger than six months of age, those with moderate to severe dehydration, children receiving care in a region where severe disease and dehydration are common, and those at risk for electrolyte abnormalities.” He also favors electrolyte solutions for children with other significant medical conditions.

Reference: Freedman SB, et al. Effect of Dilute Apple Juice and Preferred Fluids vs Electrolyte Maintenance Solution on Treatment Failure Among Children With Mild Gastroenteritis: A Randomized Clinical Trial. JAMA. 2016;315(18):1966-1974.

Abstract: http://jama.jamanetwork.com/article.aspx?articleid=2518402

C. Babies less likely to get flu if mom gets vaccinated during pregnancy

Research showed infants ages 6 months and younger were 70% less likely to get the flu if their moms got the flu vaccine during pregnancy, compared with those whose mothers were not vaccinated. The study, published in Pediatrics, also found an 80% decrease in flu-related hospitalizations among infants whose mothers were vaccinated during pregnancy.

Abstract: http://pediatrics.aappublications.org/content/early/2016/04/30/peds.2015-2360

D. BRUE, the new ALTE: American Academy of Pediatrics refines guideline on what's called a 'brief resolved unexplained event’

Temporarily Turning Blue Sometimes Normal for Babies

MONDAY, April 25, 2016 (HealthDay News) -- It's a heart-stopping moment experienced by many parents -- they discover their baby has turned blue, is breathing irregularly, or won't respond to a gentle wake-up nudge. Yet, mere seconds later the infant is back to normal.

Fortunately, these events are less dire than one might think. But they're also more common, an expert panel from the American Academy of Pediatrics (AAP) concluded.

The AAP panel has coined a new term for these events, to reflect the fact that they are rarely associated with a serious underlying medical problem. The new term, "brief resolved unexplained events" or BRUE, replaces the previous term, "apparent life-threatening events" or ALTE, said Dr. Joel Tieder, lead author of the new AAP clinical practice guideline. Tieder is an associate professor of medicine at Seattle Children's Hospital.

A BRUE is transient in nature, and has no clear cause, the new guideline said.

BRUE episodes happen in babies younger than 1 year of age when one or more of the following conditions occurs:

• Turning blue or pale
• Irregular, decreased or halted breathing
• A marked change in muscle tone
• Unresponsiveness.

The episode must last less than a minute, and then resolve itself on its own, the panel said.

"Infants probably do these things regularly and we don't know it," said Dr. Ian Holzman, chief of newborn medicine at Mount Sinai Hospital in New York City. "I think that's the gist of it. This is something that's not a disease, not a sickness. It happens, and you don't have to get crazy about it."

Tieder explained that the term ALTE was applied to these events back in the 1980s, when doctors thought they might be precursors to sudden infant death syndrome (SIDS). But ALTE was poorly defined and led to many children being hospitalized and receiving unnecessary testing, Tieder said. Pediatricians would draw blood, attach EKG wires and order radiation-laden imaging scans, but often found nothing wrong with the child.

"Those tests oftentimes didn't lead to a diagnosis, and when they did lead to a diagnosis it wasn't something that wasn't a treatable diagnosis," Tieder said. "We really had to ask the question, are we doing more harm for these families than good?" In addition, research has since determined that these events are not related to SIDS, Tieder added, noting that this finding is very reassuring for parents. BRUE will be applied to cases based on more tightly defined criteria than those given to ALTE, he said.

Pediatricians can diagnose an event as BRUE only after performing a physical examination and taking a medical history, which is another marked change from the way ALTE was applied, Tieder explained. Doctors often diagnosed ALTE based solely on what they were told by the parent or caregiver. The truth is, these sort of events just happen to babies, the AAP panel concluded.

Tieder noted a key study that tracked about 1,000 infants over a couple of weeks on home monitors. "When you look at those kids, even the healthy kids, these types of events were quite common," he said. But, he added, they're not always seen in the health care setting.

The BRUE episodes are related to things that occur regularly to infants. "Infants don't come with a manual, and they do things parents wouldn't expect," Tieder said. For example, it's part of normal infant physiology to stop breathing for brief periods, or to occasionally turn blue at the mouth or feet, he said. Sometimes infants sleep so deeply that they appear unresponsive.

Holzman doesn't expect any controversy over the new term BRUE, although there may be a short period of "rocky disagreements for what needs to be done for children who are now BRUE."

The AAP expert panel recommends against subjecting kids with "low-risk" BRUE to hospitalization or testing. Babies with "high-risk" BRUE are those who:

• Were born premature,
• Are younger than 2 months old,
• Have had repeated BRUE episodes,
• Have had an event that lasted longer than one minute or required CPR from a trained medical professional,
• Had a finding of concern in their physical exam or medical history.

These "high-risk" kids should be given a closer look to make sure nothing's wrong, Tieder said.

Although the new term is meant to reassure parents, babies should still be examined by a doctor following what appears to be a BRUE episode, Tieder and Holzman said. "The important part is that the baby otherwise seems fine, but I think it still merits some other person making sure the child is healthy," Holzman said.

The new AAP clinical guideline was released online April 25 and published in the May print issue of the journal Pediatrics.

The new AAP Guidelines (full-text free): http://pediatrics.aappublications.org/content/early/2016/04/21/peds.2016-0591

E. Free eBooks on Pediatric EM

1. PEM Guides 2.0 by Michael Mojica, MD, NYU Langone Medical Center

The author writes: “PEM (Pediatric Emergency Medicine) Guides was developed as a point of care resource in our pediatric emergency departments at Bellevue Hospital Center and NYU Langone Medical Center. The PEM Guides focus on the essential diagnostic, treatment and disposition decisions.”

Link: https://itunes.apple.com/us/book/pem-guides/id1039923332?mt=11

2. EM Cases Digest Volume 2: Pediatric Emergencies

EM Cases Digest Volume 2 has officially been released and available for download exclusively here on the EM Cases website. This will be the second release of six Free Open Access Medical Education eBooks that will cover six pillars of Emergency Medicine. Each one is designed specifically to maximize your EM learning with interactive cases, Q&As, pearls & pitfalls, updates, images, videos, links to top-notch resources and references drawn from the library of more than 150 EM Cases podcasts to date. The EM Cases Team in collaboration with 9 authors has been working diligently over the past year to bring you this second eBook of the series.

Emergency Medicine Cases (EM Cases) is a free online medical education podcast, medical blog and website dedicated to providing online emergency medicine education and CME for physicians, residents, students nurses and paramedics. We are Canada’s most listened to emergency medicine podcast with thousands of subscribers, well over a million and a half podcast downloads since 2010 and are proudly part of the #FOAMed community.

Link: http://emergencymedicinecases.com/em-cases-digest/

5. ECG Evolution in a Woman Presenting with Alcohol Withdrawal Seizures and Cocaine Use

Chou J, et al. JAMA Intern Med. 2016;176(5):693-695.

A postmenopausal woman with a history of alcohol abuse complicated by withdrawal seizures (last occurring 4 months prior), crack cocaine abuse, and depression was brought into the emergency department for altered mental status after 3 witnessed seizures. Her partner stated that the evening prior, she did not drink alcohol but did snort cocaine.

She was afebrile and arousable but not oriented. Her heart rate was 85 beats per minute and blood pressure was 135/90 mm Hg. Cardiopulmonary examination results were within normal limits, and neurologic examination revealed no focal deficits. Results from complete blood cell count and electrolyte panel were normal, and a urine toxicology screen was positive for cocaine. Results from a noncontrast head computed tomographic (CT) scan were normal. Her initial electrocardiography (ECG) test showed normal sinus rhythm with Q waves in the anterior leads and early repolarization (Figure, A). Over the next 7 hours, her mental status improved, and she remained seizure-free. The patient was about to be discharged when ST-segment elevations were noted on the MCL3 telemetry lead. A 12-lead ECG demonstrated ST-segment elevations in leads V3 to V6 (Figure, B). On further questioning, the patient reported a 1-day history of mild, constant, nonradiating, non–nitroglycerin-responsive chest ache at rest but denied exertional chest pain. Her troponin level, drawn when the ST-segment elevations were noted, was 3.2 ng/mL.

Despite these ECG changes, the patient denied any crushing or pressure-like chest pain and was in no acute distress. Bedside ultrasonography demonstrated dyskinesis of the left ventricular apex. She was transferred to the cardiology service for monitoring, given aspirin, 325 mg, atorvastatin, 80 mg, and begun on a heparin drip. She was not taken emergently to cardiac catheterization, given the atypical history and quality of chest discomfort and the ultrasonographic finding of left apical ballooning, which was highly suspicious, but not diagnostic for stress (takotsubo) cardiomyopathy. Repeated ECG 4 hours later demonstrated persistent ST-segment elevations in V3, as well as new T-wave inversions (TWIs) in leads V4 to V6 (Figure, C). The troponin level decreased to 2.6 ng/mL. A transthoracic echocardiogram revealed akinesis of the left ventricular apex, apical ballooning, and a hyperdynamic base; the ejection fraction was 40% to 45%. The patient underwent coronary angiography the next morning, which demonstrated diffuse nonobstructive coronary disease without evidence of vasospasm. Given these findings, the patient’s clinical presentation was consistent with stress cardiomyopathy, and the heparin drip was discontinued. Another ECG 48 hours after initial presentation demonstrated deepening and more diffuse TWIs and a prolonged QT interval (Figure, D).

Over the next day, the patient was free of chest pain. Further medical history revealed that she was under considerable family and financial stress, and was being evicted from her apartment. She had recently increased her alcohol consumption and crack cocaine use to help deal with these issues. At discharge, the patient was prescribed metoprolol succinate, 25 mg, and lisinopril, 5 mg, and counseled regarding her polysubstance abuse. Given her poor medication compliance, she was not prescribed anticoagulation drugs. An echocardiogram performed 3 months later demonstrated complete normalization of the left ventricular wall motion and ejection fraction…

Images, discussion of stress cardiomyopathy, and references (free): http://archinte.jamanetwork.com/article.aspx?articleid=2504180

6. Association of Fluid Resus Initiation within 30 Minutes of Severe Sepsis and Septic Shock Recognition with Reduced Mortality and Length of Stay.

Leisman D, et al. Ann Emerg Med 2016 Apr 14 [Epub ahead of print]

STUDY OBJECTIVE: We evaluate the association of intravenous fluid resuscitation initiation within 30 minutes of severe sepsis or septic shock identification in the emergency department (ED) with inhospital mortality and hospital length of stay. We also compare intravenous fluid resuscitation initiated at various times from severe sepsis or septic shock identification's association with the same outcomes.

METHODS: This was a review of a prospective, observational cohort of all ED severe sepsis or septic shock patients during 13 months, captured in a performance improvement database at a single, urban, tertiary care facility (90,000 ED visits/year). The primary exposure was initiation of a crystalloid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification. Secondary analysis compared intravenous fluid initiated within 30, 31 to 60, or 61 to 180 minutes, or when intravenous fluid resuscitation was initiated at greater than 180 minutes or not provided.

RESULTS: Of 1,866 subjects, 53.6% were men, 72.5% were white, mean age was 72 years (SD 16.6 years), and mean initial lactate level was 2.8 mmol/L. Eighty-six percent of subjects were administered intravenous antibiotics within 180 minutes; 1,193 (64%) had intravenous fluid initiated within 30 minutes. Mortality was lower in the within 30 minutes group (159 [13.3%] versus 123 [18.3%]; 95% confidence interval [CI] 1.4% to 8.5%), as was median hospital length of stay (6 days [95% CI 6 to 7] versus 7 days [95% CI 7 to 8]). In multivariate regression that included adjustment for age, lactate, hypotension, acute organ dysfunction, and Emergency Severity Index score, intravenous fluid within 30 minutes was associated with lower mortality (odds ratio 0.63; 95% CI 0.46 to 0.86) and 12% shorter length of stay (hazard ratio=1.14; 95% CI 1.02 to 1.27). In secondary analysis, mortality increased with later intravenous fluid resuscitation initiation: 13.3% (≤30 minutes) versus 16.0% (31 to 60 minutes) versus 16.9% (61 to 180 minutes) versus 19.7% (beyond 180 minutes). Median hospital length of stay also increased with later intravenous fluid initiation: 6 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 8 days) versus 8 days (95% CI 7 to 9 days).

CONCLUSION: The time of intravenous fluid resuscitation initiation was associated with improved mortality and could be used as an easier obtained alternative to intravenous fluid completion time as a performance indicator in severe sepsis and septic shock management.

7. Wells Rule and d-Dimer Testing to Rule Out PE: A Systematic Review and Individual-Patient Data Meta-analysis.

van Es N, et al. Ann Intern Med. 2016 May 17. doi: 10.7326/M16-0031. [Epub ahead of print]

Background: The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear.

Purpose: To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older.

Data Sources: MEDLINE and EMBASE from 1 January 1988 to 13 February 2016.

Study Selection: 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing.

Data Extraction: Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool.

Data Synthesis: The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged over 50 years) d-dimer thresholds; their 3-month incidence of symptomatic venous thromboembolism (failure rate) was also estimated. Overall, efficiency increased from 28% to 33% when the age-adjusted (instead of the fixed) d-dimer threshold was applied. This increase was more prominent in elderly patients (12%) but less so in inpatients (2.6%). The failure rate of age-adjusted d-dimer testing was less than 3% in all examined subgroups.

Limitation: Post hoc analysis, between-study differences in patient characteristics, use of various d-dimer assays, and limited statistical power to assess failure rate.

Conclusion: Age-adjusted d-dimer testing is associated with a 5% absolute increase in the proportion of patients with suspected PE in whom imaging can be safely withheld compared with fixed d-dimer testing. This strategy seems safe across different high-risk subgroups, but its efficiency varies.

8. Urgent Care Needs among Nonurgent Visits to the ED

Hsia RY, et al. JAMA Intern Med 2016 Apr 18 [Epub ahead of print]

The goal of triage is to prioritize patients who need to be seen most urgently; it is essential for providing the highest quality of care to the sickest patients.1 We sought to determine whether a triage determination of nonurgent status in the emergency department (ED) effectively ruled out the possibility of serious pathologic conditions, as indicated by visits resulting in diagnostic screening, procedures, hospitalization, or death, and compared these findings with visits deemed as urgent from triage.
 
The National Hospital Ambulatory Medical Care Survey is a national multistage probability sample survey of patient visits to the ED. These data contain triage scores for each ED visit as assessed by a triage nurse on arrival based on a scale of 1 to 5, with 1 being immediate, 2 emergent, 3 urgent, 4 semi-urgent, and 5 nonurgent.2 We compared characteristics and outcomes of visits from January 1, 2009, to December 31, 2011, labeled as nonurgent (category 5) with characteristics and outcomes of visits with all other labels (categories 1-4), which we labeled as urgent visits. We focused on nonelderly adults aged 18 to 64 years and excluded visits for which triage scores were missing or where the patient left before triage or medical screening. This study was deemed exempt from human subjects review at the University of California San Francisco.
 
We analyzed 59 293 observations from 2009 to 2011, representing 240 million visits. A total of 218.49 million visits (92.5%) were deemed urgent at triage and 17.76 million visits (7.5%) as nonurgent. A total of 33.82 million visits (15.5%) deemed urgent arrived by ambulance, compared with 1.19 million visits (6.7%) considered nonurgent. Diagnostic services, such as blood tests, electrocardiograms, and imaging, were provided in 8.45 million nonurgent visits (47.6%) (any blood tests: weighted, 18.8% [95% CI, 15.5%-22.1%]; electrocardiograms: 5.8% [95% CI, 4.3%-7.2%]; and any imaging: 28.5% [95% CI, 24.9%-32.0%]), and procedures, such as intravenous fluids, casting, and splinting, were performed in 5.76 million nonurgent visits (32.4%) (intravenous fluids: weighted, 12.6% [95% CI, 9.7%-15.6%]; casting: 0.6% [95% CI, 0.2%-1.0%]; and splinting: 6.2% [95% CI, 5.2%-7.3%]). In comparison, diagnostic services were provided in 163.49 million urgent visits (74.8%) (any blood tests: weighted, 46.2% [95% CI, 44.7%-47.6%]; electrocardiograms: 18.7% [95% CI, 17.8%-19.6%]; and any imaging: 49.0% [95% CI, 47.7%-50.3%]), and procedures were performed in 107.89 million urgent visits (49.4%) (intravenous fluids: weighted, 31.7% [95% CI, 30.2%-33.3%]; casting: 0.3% [95% CI, 0.2%-0.3%]; and splinting: 5.6% [95% CI, 5.3%-5.9%]) (P  less than  .001 for all comparisons) (Table 1).
 
A total of 776 000 nonurgent visits (weighted, 4.4% [95% CI, 3.1%-5.7%]) resulted in admissions and of these, 126 000 (16.2%; weighted, 0.7% (95% CI, 0.1%-1.3%]) were admissions to critical care units. A total of 27.86 million urgent visits (weighted, 12.8% [95% CI, 11.7%-13.8%]) resulted in admissions (P  less than  .001), of which only 2.91 million (10.5%; weighted, 1.3% (95% CI, 1.2%-1.5%]) (P = .32) were admissions to critical care units. Overall, 1.01 million nonurgent visits (weighted, 5.7% [95% CI, 4.2%-7.1%]) resulted in admission or transfer, compared with 32.49 million urgent visits (weighted, 14.9% [95% CI, 13.8%-15.9%]) (P  less than  .001) (Table 2).
 
When we examined the chief symptoms reported at nonurgent visits, 6 of the top 10 reasons—back symptoms, abdominal pain, sore throat, headache, chest pain, and low back pain—were also in the top 10 symptoms reported at urgent visits. In addition, when the top 10 diagnoses from nonurgent visits were analyzed, 5 were identical to those at urgent visits (backache, lumbago, acute upper respiratory infection, cellulitis, and acute pharyngitis).
 
Our study found that a nontrivial proportion of ED visits that were deemed nonurgent arrived by ambulance, received diagnostic services, had procedures performed, and were admitted to the hospital, including to critical care units. Certainly, not all of these data necessarily indicate that these services were required, and they could signal overuse or a lack of availability of primary care physicians.3 However, to some degree, our findings indicate that either patients or health care professionals do entertain a degree of uncertainty that requires further evaluation before diagnosis. That half of the top 10 diagnoses, among over 14 000 International Classification of Diseases, Ninth Revision codes, are found in both nonurgent and urgent visits shows that 50% of these visits are virtually indistinguishable from each other.
 
There are certain limitations to this study. Specifically, while the National Hospital Ambulatory Medical Care Survey uses a 5-level triage score, not all hospitals do. The National Hospital Ambulatory Medical Care Survey therefore rescales visits to hospitals that do not use a 5-level triage score, and also imputes missing values. When we repeated our analysis without imputed values, we found similar results.
 
The original intention of triage—to predict the amount of time a patient could safely wait to be seen in the ED—was never intended to completely rule out the possibility of severe illness in a patient considered nonurgent. However, the rhetoric behind the term nonurgent has been often politicized to mean inappropriate, which has implications for both the patient and health care system when these 2 terms are conflated. Our findings highlight the lack of certainty of nonurgent status even when it is determined prospectively by a provider at triage and suggest that caution must be taken when using triage scores beyond their intended purpose.

9. Research warns of overtreatment with heart disease risk calculator

A Kaiser Permanente study published in the Journal of the American College of Cardiology found that patients may be receiving unnecessary treatment for heart disease risk based on guidelines issued in 2013. Researchers examined data from more than 300,000 Kaiser members, finding that the risk calculator overestimates five-year risk of heart problems by five- to sixfold.

Essay in Time Magazine: http://time.com/4313978/heart-disease-stroke-risk/

Reference: Rana JS, et al. Accuracy of the Atherosclerotic Cardiovascular Risk Equation in a Large Contemporary, Multiethnic Population. J Am Coll Cardiol. 2016 May 10;67(18):2118-30.

Abstract: The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood.

Objectives: The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care.

Methods: The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels less than 70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus.

Results: Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk less than 2.50%; 0.65% for predicted risk 2.50% to less than 3.75%; 0.90% for predicted risk 3.75% to less than 5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64).

Conclusions: In a large, contemporary “real-world” population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups.

Full-text (free): http://www.sciencedirect.com/science/article/pii/S0735109716010251

10. Images in Clinical Practice

Splenosis Mimicking Cancer

http://www.nejm.org/doi/full/10.1056/NEJMicm1512086

Diaphragmatic Hernia Causing Lung Collapse

http://www.nejm.org/doi/full/10.1056/NEJMicm1415660

Hair-on-End Sign

http://www.nejm.org/doi/full/10.1056/NEJMicm1510045

Petaloid Cataract

http://www.nejm.org/doi/full/10.1056/NEJMicm1507349

Aortocoronary Saphenous-Vein–Graft Aneurysms

http://www.nejm.org/doi/full/10.1056/NEJMicm1508440

11. High single-dose vancomycin loading is not associated with increased nephrotoxicity in ED sepsis patients.

Rosini JM, et al. Acad Emerg Med. 2016 Feb 6 [Epub ahead of print]

OBJECTIVE: Vancomycin loading doses are recommended, however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (over 20 mg/kg) versus lower doses (≤20 mg/kg).

METHODS: A retrospective cohort study was performed in three academic EDs.

INCLUSION CRITERIA: age ≥ 18 years, IV vancomycin order, and hospital admission.

EXCLUSION CRITERIA: no documented weight, hemodialysis-dependent, inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (over 20 mg/kg) vs. low dose (≤20 mg/kg).

RESULTS: A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs 11.1%). After adjusting for age, gender, and initial SCr, the risk of high dose vancomycin compared to low dose was decreased for the development of nephrotoxicity (RR=0.60; 95% CI: 0.44, 0.82).

CONCLUSION: Initial dosing of vancomycin over 20 mg/kg, was not associated with an increased rate of nephrotoxicity compared with lower doses. Findings from this study support compliance with initial weight-based vancomycin loading doses.

Full-text (free): http://onlinelibrary.wiley.com/doi/10.1111/acem.12934/full

12. Out-of-Hospital Cardiac Arrest — Are Drugs Ever the Answer?

Joglar JA, et al. N Engl J Med 2016; 374:1781-1782.

Editorial on Kudenchuk PJ, et al. Resuscitation Outcomes Consortium (ROC) Investigators. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016; 374(18):1711-22. Full-text (free): http://www.nejm.org/doi/full/10.1056/NEJMoa1514204#t=article 

Out-of-hospital cardiac arrest accounts for approximately 356,000 deaths per year in the United States,1 with many patients having ventricular fibrillation or pulseless ventricular tachycardia as the presenting rhythm. In an effort to reduce mortality, the American Heart Association (AHA) developed the “Chain of Survival,”2 including early cardiopulmonary resuscitation (CPR), rapid defibrillation, and “effective advanced life support” as central links in management. However, the rate of survival of out-of-hospital cardiac arrest with good neurologic function remains poor, averaging just 8.5%.1 Geographic variation exists, and higher rates of survival are reported in specific locations such as aircraft3 and casinos.4

Defibrillation is effective at terminating most sustained ventricular fibrillation or pulseless ventricular tachycardia, but the arrhythmia persists in some patients, and many have immediate recurrence. Antiarrhythmic medication, typically intravenous amiodarone or lidocaine, is often used with the goal of restoring and maintaining a stable rhythm. Both agents have a class IIb recommendation in the 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,5 which states that these drugs “may be considered” for ventricular fibrillation or pulseless ventricular tachycardia that “is unresponsive to CPR, defibrillation, and a vasopressor therapy.”5 The uncertainty in these recommendations is based on previous trials6,7 that were not powered to make comparisons with respect to overall survival and that showed no survival benefit. Furthermore, all previous trials of intravenous amiodarone were potentially undermined by a formulation that included a solvent that causes hypotension; thus, the effect purely of the drug had not been evaluated. In this context, the Resuscitation Outcomes Consortium (ROC) conducted a trial to address an important question: are drugs the answer? The results of this trial are now reported by Kudenchuk et al.8 in the Journal.

The ROC is a network of regional centers across North America, supported by the National Institutes of Health and other organizations, that allows for well-powered randomized studies of out-of-hospital cardiac arrest and trauma. The trial is the first randomized, multicenter, double-blind comparison of intravenous saline placebo versus amiodarone versus lidocaine, along with standard care, in patients with out-of-hospital cardiac arrest and ventricular fibrillation or pulseless ventricular tachycardia that recurs or persists after one or more electrical shocks. Although the lidocaine preparation is standard, the formulation of amiodarone with a solvent that does not cause hypotension (Nexterone, Baxter Healthcare) is novel and allows for isolated evaluation of the pharmacologic effect of the drug.

In the trial, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival to hospital discharge (the primary outcome) or favorable neurologic function at discharge (the secondary outcome) than the rate with placebo among the 3026 patients studied. On the other hand, there were nonsignificant differences between each drug and placebo in the survival rate (a difference of 3.2 percentage points for amiodarone vs. placebo and 2.6 percentage points for lidocaine vs. placebo). Further evidence of an antiarrhythmic effect was the significant benefit of both drugs over placebo in several measures: fewer shocks were administered after the first dose of the trial drug; fewer patients received rhythm-control medications during hospitalization; and fewer patients required CPR during hospitalization.

How might we explain the negative results of the trial? One possibility, as the authors suggest, is that the trial was underpowered for the smaller-than-predicted drug effect. A further possibility is that drug delivery was provided too late to overcome the metabolic consequences of prolonged arrest. Rates of conversion to sinus rhythm and survival rates are highest immediately after out-of-hospital cardiac arrest, with up to 74% survival among patients with ventricular fibrillation or pulseless ventricular tachycardia if a shock is administered within 3 minutes.4 This brief “electrical phase” is followed by a “hemodynamic phase”; however, after 10 minutes, the “metabolic phase” dominates and the chances of survival are reduced.9

For the vast majority of the trial patients (for whom emergency medical services [EMS] personnel were not present at the time of arrest), the mean time to drug treatment was 19.3 minutes — well into the metabolic phase. What if the drug therapy were administered sooner, as we might presume would occur for the substantial subgroup (66%) whose arrest was witnessed by a bystander? For these patients, the rate of survival to hospital discharge was significantly higher with amiodarone (27.7%) or lidocaine (27.8%) than with placebo (22.7%) — a clinically important difference of 5 percentage points.

What can we conclude from the current trial, and how might we modify care for out-of-hospital cardiac arrest with ventricular fibrillation or pulseless ventricular tachycardia that either recurs or persists despite electrical shock? The data do not support the use of amiodarone or lidocaine for all patients, but, although they are not absolutely conclusive, the data suggest that EMS personnel should consider these agents when the arrest is witnessed. There is no signal from the data as to which drug might be preferable, however.

We commend the ROC investigators for their efforts to provide scientific evidence to support emergency care, and we agree with the Institute of Medicine recommendations10 that research must continue, with efforts to coordinate emergency care and quickly implement best practices on the basis of contemporary data. Finally, we emphasize the benefit of bystander-initiated CPR, for which the current trial showed an absolute survival benefit of almost 10 percentage points, eclipsing any effect of drug intervention.

13. Treatment with Prothrombin Complex Concentrate to Enable Emergency LP in Patients Receiving Vitamin K Antagonists.

Laible M et al. Ann Emerg Med 2016 Apr 14 [Epub ahead of print]

STUDY OBJECTIVE: Lumbar punctures are frequently necessary in neurologic emergencies, but effective oral anticoagulation with vitamin K antagonists represents a contraindication. We report the effectiveness of prothrombin complex concentrates to reverse vitamin K antagonist to enable emergency lumbar punctures, as well as evaluate lumbar puncture- and prothrombin complex concentrates-related complications.

METHODS: Consecutive patients treated with prothrombin complex concentrates between December 2004 and June 2014 to enable emergency lumbar puncture were included. International normalized ratio (INR) before and after prothrombin complex concentrates treatment and the time between start of reversal treatment and lumbar puncture were recorded. A target INR of less than or equal to 1.5 was defined as effective prothrombin complex concentrates treatment. Bleeding events, thromboembolic events, and allergic reactions after prothrombin complex concentrates treatment were identified and classified as "related," "probably," "possibly," "unlikely related," or "not related" to the lumbar puncture and prothrombin complex concentrates infusion.

RESULTS: Thirty-seven patients were included (64.9% men; median age 76.0 years; interquartile range [IQR] 71.0 to 84.0 years). The intervention with prothrombin complex concentrates was effective in 33 of 37 patients (89.2%; 95% confidence interval [CI], 78.4% to 97.3%). The median INR was 2.2 (IQR 1.8 to 2.9; 95% CI, 1.9 to 2.5) before and 1.3 (IQR 1.2 to 1.4; 95% CI, 1.2 to 1.3) after prothrombin complex concentrates treatment. The median time between start of prothrombin complex concentrates treatment and lumbar puncture was 135 minutes (IQR 76 to 266 minutes; 95% CI, 84 to 198 minutes). One clinically irrelevant intracranial subdural hematoma "related" to the lumbar puncture developed. No allergic reaction was observed, but 2 of 37 patients (5.4%; 95% CI, 0% to 13.5%) experienced a thromboembolic event (1 ischemic stroke, classified "unlikely related," and 1 myocardial infarction, "possibly related" to prothrombin complex concentrates treatment).

CONCLUSION: Reversing the effect of vitamin K antagonist with prothrombin complex concentrates to enable emergency lumbar puncture appears effective and safe, particularly in regard to bleeding events.

See also “Risk of Procedural Hemorrhage”

Wolfe KS, et al. Thorax. 2 February 2016 [Epub ahead of print] (from Lit Bits: Feb 209, 2016)

Excerpt on LP

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

Full-text (free): http://www.sciencedirect.com/science/article/pii/S0012369216005171

14. Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis.

Rodrigues FB, et al. BMJ. 2016 Apr 18;353:i1754.

OBJECTIVES:  To evaluate the efficacy and safety of endovascular treatment, particularly adjunctive intra-arterial mechanical thrombectomy, in patients with ischaemic stroke.

DESIGN:  Systematic review and meta-analysis.

DATA SOURCES:  Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, SciELO, LILACS, and clinical trial registries from inception to December 2015. Reference lists were crosschecked.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES:  Randomised controlled trials in adults aged 18 or more with ischaemic stroke comparing endovascular treatment, including thrombectomy, with medical care alone, including intravenous recombinant tissue plasminogen activator (rt-PA). Trial endpoints were functional outcome (modified Rankin scale scores of ≤2) and mortality at 90 days after onset of symptoms. No language or time restrictions applied.

RESULTS:  10 randomised controlled trials (n=2925) were included. In pooled analysis endovascular treatment, including thrombectomy, was associated with a higher proportion of patients experiencing good (modified Rankin scale scores ≤2) and excellent (scores ≤1) outcomes 90 days after stroke, without differences in mortality or rates for symptomatic intracranial haemorrhage, compared with patients randomised to medical care alone, including intravenous rt-PA. Heterogeneity was high among studies. The more recent studies (seven randomised controlled trials, published or presented in 2015) proved better suited to evaluate the effect of adjunctive intra-arterial mechanical thrombectomy on its index disease owing to more accurate patient selection, intravenous rt-PA being administered at a higher rate and earlier, and the use of more efficient thrombectomy devices. In most of these studies, more than 86% of the patients were treated with stent retrievers, and rates of recanalisation were higher (over 58%) than previously reported. Subgroup analysis of these seven studies yielded a risk ratio of 1.56 (95% confidence interval 1.38 to 1.75) for good functional outcomes and 0.86 (0.69 to 1.06) for mortality, without heterogeneity among the results of the studies. All trials were open label. Risk of bias was moderate across studies. The full results of two trials are yet to be published.

CONCLUSIONS:  Moderate to high quality evidence suggests that compared with medical care alone in a selected group of patients endovascular thrombectomy as add-on to intravenous thrombolysis performed within six to eight hours after large vessel ischaemic stroke in the anterior circulation provides beneficial functional outcomes, without increased detrimental effects.

Full-text (free): http://www.bmj.com/content/353/bmj.i1754

15. Study Identifies 5 Strategies to Spark Patient Motivation

March 29, 2016 02:15 pm Paula Haas – Primary care physicians increasingly are assessed on patient outcomes even though many outcomes are determined largely by the patient, not the physician. But physicians sometimes struggle with motivating patients to make health-enhancing changes.

A research study (www.annfammed.org) published in the March/April issue of Annals of Family Medicine identified five strategies that may help. The strategies show promise in supporting patient activation, which has been shown to be associated with outcomes including better self-management and clinical indicators, fewer hospitalizations and lower health care costs.

The study, "Supporting Patient Behavior Change: Approaches Used by Primary Care Clinicians Whose Patients Have an Increase in Activation Levels," defined patient activation as having the knowledge, confidence and skills to take care of one's health and health care.

Using data from an accountable care organization, researchers aggregated data on change in the patient activation measure (PAM) scores for 7,144 patients to the primary care clinician level. The patients all had two PAM scores between 2010 and 2012, and were chosen based on their baseline scores being below the highest of four levels of scores.

"We found the top-performing clinicians most frequently reported using five strategies when they worked with patients on behavior change," lead researcher Jessica Greene, Ph.D., associate dean for research and a professor at the George Washington University School of Nursing, told AAFP News.

The five key strategies were:

1. Emphasizing patient ownership. The top-performing clinicians described emphasizing that patients own their health, Greene said. "One clinician told her patients, 'I'm here to coach you, not to make you better. You make yourself better; I can't do that for you.'"

2. Partnering with patients. The top performers described working with patients to co-create goals and strategies for behavior change and to solve problems, Greene said. "These clinicians acknowledged that they don't know their patients' lives outside the clinic and that patients can best decide which goals and strategies are most appealing or feasible."

3. Identifying small steps. The top performers helped patients identify small steps toward change, initially setting the bar low so the patient could achieve the goal, said Greene. "The patient then had some confidence when the bar was set a little higher for the next step." Many of the top performers said they would ask a patient who resisted change to identify just one small change. "The patient almost always could describe one thing they could do to get healthier," said Greene.

4. Scheduling frequent follow-ups. Following up with patients frequently was part of the coaching role the top performers assumed. Some had patients come in for face-to-face visits, while others used their electronic medical record system to communicate with patients, said Greene. "A few said they felt a tension about asking a patient to make frequent follow-up visits because they didn't want the patient to have to spend more money."

5. Showing care and concern. "Some of these top-performing clinicians told patients they wanted them to be healthy enough to play with their grandchildren," Greene said. "The clinicians wanted patients to make changes so their lives would be better, not just change to please the clinician."

Very few of the bottom-performing clinicians reported using these five strategies…

The rest of the essay: http://www.aafp.org/news/practice-professional-issues/20160329motivationstudy.html

The study (full-text free): http://www.annfammed.org/content/14/2/148.full.pdf+html

16. Association of Guideline-concordant Acute Asthma Care in the ED with Shorter Hospital Length of Stay: A Multicenter Observational Study.

Hasegawa K, et al. Acad Emerg Med. 2016 May;23(5):616-22.

OBJECTIVES: The objectives were to determine whether guideline-concordant emergency department (ED) management of acute asthma is associated with a shorter hospital length of stay (LOS) among patients hospitalized for asthma.

METHODS: A multicenter chart review study of patients aged 2-54 years who were hospitalized for acute asthma at one of the 25 U.S. hospitals during 2012-2013. Based on level A recommendations from national asthma guidelines, we derived four process measures of ED treatment before hospitalization: inhaled β-agonists, inhaled anticholinergic agents, systemic corticosteroids, and lack of methylxanthines. The outcome measure was hospital LOS.

RESULTS: Among 854 ED patients subsequently hospitalized for acute asthma, 532 patients (62%) received care perfectly concordant with the four process measures in the ED. Overall, the median hospital LOS was 2 days (interquartile range = 1-3 days). In the multivariable negative binomial model, patients who received perfectly concordant ED asthma care had a significantly shorter hospital LOS (-17%, 95% confidence interval [CI] = -27% to -5%, p = 0.006), compared to other patients. In the mediation analysis, the direct effect of guideline-concordant ED asthma care on hospital LOS was similar to that of primary analysis (-16%, 95% CI = -27% to -5%, p = 0.005). By contrast, the indirect effect mediated by quality of inpatient asthma care was not significant, indicating that the effect of ED asthma care on hospital LOS was mediated through pathways other than quality of inpatient care.

CONCLUSION: In this multicenter observational study, patients who received perfectly concordant asthma care in the ED had a shorter hospital LOS. Our findings encourage further adoption of guideline-recommended emergency asthma care to improve patient outcomes.

Full-text (free): http://onlinelibrary.wiley.com/doi/10.1111/acem.12920/full

17. Predicting Outcomes in Drowning

Submersion duration may be the most important factor.

Quan L et al. Predicting outcome of drowning at the scene: A systematic review and meta-analyses. Resuscitation 2016 May 3 [Epub ahead of print]

OBJECTIVE: To identify factors available to rescuers at the scene of a drowning that predict favourable outcomes.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: PubMed, Embase and Cochrane Library were searched (1979-2015) without restrictions on age, language or location and references lists of included articles.

STUDY SELECTION: Cohort and case-control studies reporting submersion duration, age, water temperature, salinity, emergency services response time and survival and/or neurological outcomes were eligible. Two reviewers independently screened articles for inclusion, extracted data, and assessed quality using GRADE. Variables for all factors, including time and temperature intervals, were categorized using those used in the articles. Random effects meta-analyses, study heterogeneity and publication bias were evaluated.

RESULTS: Twenty-four cohort studies met the inclusion criteria. The strongest predictor was submersion duration. Meta-analysis showed that favourable outcome was associated with shorter compared to longer submersion durations in all time cutoffs evaluated: ≤5-6min: risk ratio [RR]=2.90; (95% confidence interval [CI]: 1.73, 4.86); ≤10-11min: RR=5.11 (95% CI: 2.03, 12.82); ≤15-25min: RR=26.92 (95% CI: 5.06, 143.3). Favourable outcomes were seen with shorter EMS response times (RR=2.84 (95% CI: 1.08, 7.47)) and salt water versus fresh water 1.16 (95% CI: 1.08, 1.24). No difference in outcome was seen with victim's age, water temperatures, or witnessed versus unwitnessed drownings.

CONCLUSIONS: Increasing submersion duration was associated with worse outcomes. Submersion durations less than 5min were associated with favourable outcomes, while those beyond 25min were invariably fatal. This information may be useful to rescuers and EMS systems deciding when to perform a rescue versus a body recovery.

18. Oral Anticoagulants: Exploring the Newer Agents

A. Which Oral Anticoagulant for Atrial Fibrillation?

Med Lett Drugs Ther. 2016 Apr 11;58(1492):45-6.

Direct-to-consumer advertisements continue to urge patients who take warfarin (Coumadin, and others) for atrial fibrillation to ask their doctors about the benefits of one or another of the newer oral anticoagulants.

WARFARIN — In patients with nonvalvular atrial fibrillation, warfarin reduces the risk of thromboembolic stroke by about 60%.1 If necessary, vitamin K, prothrombin complex concentrate, or fresh frozen plasma can reverse its anticoagulant effect.2 Drawbacks of warfarin include unpredictability and variability in dosage requirements, dietary restrictions, interactions with many other drugs, and the need for close monitoring to keep the international normalized ratio (INR) in the therapeutic range (2-3).

DIRECT ORAL ANTICOAGULANTS — The direct thrombin inhibitor dabigatran etexilate (Pradaxa) and the direct factor Xa inhibitors apixaban (Eliquis), edoxaban (Savaysa), and rivaroxaban (Xarelto) do not require routine monitoring of coagulation times and they have fewer drug interactions than warfarin.

Drawbacks of the direct oral anticoagulants include absence of any method for monitoring the extent of their anticoagulant effect, short half-lives that increase the risk of thrombosis with missed doses, lack of data on their use in patients with end-stage renal disease, and higher drug costs.

Efficacy – In the pivotal clinical trials against warfarin that led to their approval by the FDA, all of the direct oral anticoagulants were at least noninferior to warfarin for prevention of stroke or systemic embolism in patients with atrial fibrillation. In patients taking warfarin, the INR was in the therapeutic range only 55-65% of the time.3-6 Edoxaban was less effective than warfarin for prevention of stroke or systemic embolism in patients with a CrCl above 95 mL/min; it was more effective in those with a CrCl between 50 and 80 mL/min.7

Bleeding – All of the direct oral anticoagulants had significantly lower rates of intracranial bleeding and hemorrhagic stroke than warfarin in the pivotal clinical trials. Compared to warfarin, the rates of major bleeding with dabigatran and rivaroxaban were similar and the rates with apixaban and edoxaban were significantly lower.

Reversibility – In 2015, the FDA approved idarucizumab (Praxbind) for urgent reversal of the anticoagulant effect of dabigatran.8 No specific antidote is available in the US for the three direct factor Xa inhibitors, but in one study in healthy volunteers, an investigational synthetic product (andexanet alfa) reversed the anticoagulant effects of apixaban and rivaroxaban within minutes.9 The results of some studies suggest that the anticoagulant effects of all of the direct oral anticoagulants may be reversed by prothrombin complex concentrate.10

CONCLUSION — The direct oral anticoagulants dabigatran (Pradaxa), apixaban (Eliquis), edoxaban (Savaysa), and rivaroxaban (Xarelto) have been at least as effective as warfarin (Coumadin, and others) in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation, and they appear to be safer. Patients well controlled on warfarin (INR stable in the therapeutic range) could stay on it. For all others, one of the direct oral anticoagulants might be a better choice. Head-to-head comparisons of the new drugs are lacking.

References and tables: http://secure.medicalletter.org/TML-article-1492a

B. Coagulation assessment with the new generation of oral anticoagulants

Pollack CV. Emerg Med J  2016;33:423-430  

Long-term oral anticoagulant (OAC) therapy is used for the treatment and prevention of thrombosis and thromboembolism. As OAC use is so widespread, emergency physicians are likely to encounter patients on anticoagulant therapy in the emergency department (ED) on a regular basis, either for the same reasons as the population in general or as a result of the increased bleeding risk that OAC use entails.

The vitamin K antagonist warfarin has been the standard OAC for several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply ‘NOACs’) have become available for long-term use. Protocols for assessing and managing warfarin-treated patients in the ED are well established and include international normalised ratio (INR) testing, which helps guide patient management. However, the INR does not give an accurate evaluation of coagulation status with NOACs, and alternative tests are therefore needed for use in emergency settings. This paper discusses what information the INR provides for a patient taking warfarin and which coagulation tests can guide the physician when treating patients on one of the NOACs, as well as other differences in emergency anticoagulation management.

Full-text (free): http://emj.bmj.com/content/33/6/423.full

19. Emergency care of acute ischemic stroke patients in the Kaiser Permanente Southern California Integrated Health System.

Sauser-Zachrison K, et al. Perm J. 2016 March 25 [Epub ahead of print].

CONTEXT: Tissue plasminogen activator (tPA) is underutilized for treatment of acute ischemic stroke.

OBJECTIVE: To determine whether the probability of tPA administration for patients with ischemic stroke in an integrated health care system improved from 2009 to 2013, and to identify predictors of tPA administration.

DESIGN: Retrospective analysis of all ischemic stroke presentations to 14 Emergency Departments between 2009 and 2013. A generalized linear mixed-effects model identified patient and hospital predictors of tPA.

MAIN OUTCOME MEASURES: Primary outcome was tPA administration; secondary outcomes were door-to-imaging and door-to-needle times and tPA-related bleeding complications.

RESULTS: Of the 11,630 patients, 3.9% received tPA. The likelihood of tPA administration increased with presentation in 2012 and 2013 (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.26-2.43; and OR = 2.58; 95% CI = 1.90-3.51), female sex (OR = 1.27; 95% CI = 1.04-1.54), and ambulance arrival (OR = 2.17; 95% CI = 1.76-2.67), and decreased with prior stroke (OR = 0.47; 95% CI = 0.25-0.89) and increased age (OR = 0.98; 95% CI = 0.97-0.99). Likelihood varied by Medical Center (pseudo-intraclass correlation coefficient 13.5%). Among tPA-treated patients, median door-to-imaging time was 15 minutes (interquartile range, 9-23 minutes), and door-to-needle time was 73 minutes (interquartile range, 55-103 minutes). The rate of intracranial hemorrhage was 4.2% and 0.9% among tPA- and non-tPA treated patients (p less than 0.001).

CONCLUSION: Acute ischemic stroke care improved over time in this integrated health system. Better understanding of differences in hospital performance will have important quality-improvement and policy implications.

Full-text (free): http://www.thepermanentejournal.org/issues/2016/spring/6138-kaiser-permanente-southern-california.html

20. Applying Organizational Learning Research to Accountable Care Organizations

Nembhard IM, et al. Med Care Res Rev. March 30, 2016

To accomplish the goal of improving quality of care while simultaneously reducing cost, Accountable Care Organizations (ACOs) need to find new and better ways of providing health care to populations of patients. This requires implementing best practices and improving collaboration across the multiple entities involved in care delivery, including patients.

In this article, we discuss seven lessons from the organizational learning literature that can help ACOs overcome the inherent challenges of learning how to work together in radically new ways. The lessons involve setting expectations, creating a supportive culture, and structuring the improvement efforts. For example, with regard to setting expectations, framing the changes as learning experiences rather than as implementation projects encourages the teams to utilize helpful activities, such as dry runs and pilot tests. It is also important to create an organizational culture where employees feel safe pointing out improvement opportunities and experimenting with new ways of working. With regard to structure, stable, cross-functional teams provide a powerful building block for effective improvement efforts. The article concludes by outlining opportunities for future research on organizational learning in ACOs.

21. Managing migraine in complicated patients

Prettypaul C, et al. Acad Life in Emerg Med. 2016 May 18.

Case vignette: A 42-year-old female presents at 10 pm with a throbbing right frontal headache associated with nausea, vomiting, photophobia, and phonophobia. The headache is severe, rated as “10” on a 0 to 10 triage pain scale. The headache began gradually while the patient was at work at 2 pm. Since 2 pm, she has taken 2 tablets of naproxen 500 mg and 2 tablets of sumatriptan 100 mg without relief.

The patient has a diagnosis of migraine without aura. She reports 12 attacks per month. The headache is similar to her previous migraine headaches. She is forced to present to an Emergency Department (ED) on average 2 times per month for management of migraine refractory to oral therapy. She reports a history of dystonic reactions and akathisia after receiving IV dopamine antagonists during a previous ED visit. The physical exam is non-contributory including a normal neurological exam, normal visual fields and fundoscopic exam, and no signs of a head or face infection. When you are done evaluating her, the patient reports that she usually gets relief with 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM, and asks that you administer her usual treatment. What do you do?

Background

Migraine is a neurological disorder characterized by recurrent painful headaches and abnormal processing of sensory input resulting in symptoms such as photophobia, phonophobia, and osmophobia [1]. Central to disease pathogenesis is abnormal activation of nociceptive pathways [2]. Disease severity ranges from mild to severe. Patients at one end of the spectrum have rare episodic headaches. On the other end are patients who have headaches on more days than not, patients who are functionally impaired by their headaches, and patients who frequently cannot participate fully in work or social activities. Chronic migraine, a sub-type of migraine defined by ≥15 days with headache for at least 3 consecutive months, is experienced by 1-3% of the general population [3].

ED use for treatment of migraine is common. 1.2 million patients present to U.S. ED’s annually for management of this primary headache disorder [4]. Parenteral opioids are used to treat the acute headache in slightly more than 50% of all ED visits [4]. Multiple authorities have cautioned against the use of opioids for migraine [5,6]. However, the frequent use of opioids has continued unabated, despite the publication in the EM, neurology, and headache literature of dozens of randomized controlled trials (RCTs) demonstrating safety and efficacy of parenteral alternatives, most notably dopamine antagonists and non-steroidal anti-inflammatory drugs [7].

Opioids have been associated with a variety of poor outcomes in migraine patients including:

1. Progression of the underlying migraine disorder from episodic to chronic migraine [8]

2. Increased frequency of return visits to ED [9]

3. Less responsiveness to subsequent treatment with triptans [10]

4. Less frequent headache relief than patients who received dihydroergotamine or dopamine antagonists [11]

In contrast, a high quality, ED-based RCT did not demonstrate more harm from 1 or 2 doses of meperidine than from dihydroergotamine [12]. Hydromorphone, the parenteral opioid currently used most commonly in U.S. EDs [4], has never been studied experimentally in migraine patients. However, given the wide range of parenteral alternatives, the possibility that opioids may worsen the underlying migraine disorder, and the fact that they are less efficacious than other treatments, opioids should not be offered as first- or second-line therapy for patients who present de novo to an ED with an acute migraine (assuming no contraindications to alternative medications).

Questions

1) Other than opioids, what parenteral therapies can be offered to this patient?

2) Does the fact that this patient makes frequent use of the ED indicate an unmet medical need?

3) Should the patient be administered 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM as she wishes?

The rest of the discussion here (full-text free): https://www.aliem.com/2016/managing-migraine-headaches-complicated-patients/

22. TIA Management: Timely Specialty Care is Best

A. Inpatient Stroke Unit Better than General Ward

Patients with TIA have better survival outcomes when admitted to an inpatient specialized stroke unit.

Cadilhac DA et al. Neurology 2016 May 4 [Epub ahead of print]

OBJECTIVES: To investigate differences in management and outcomes for patients admitted to the hospital with TIA according to care on a stroke unit (SU) or alternate ward setting up to 180 days post event.

METHODS: TIA admissions from 40 hospitals participating in the Australian Stroke Clinical Registry during 2010-2013 were assessed. Propensity score matching was used to assess outcomes by treatment group including Cox proportional hazards regression to compare survival differences and other appropriate multivariable regression models for outcomes including health-related quality of life and readmissions.

RESULTS: Among 3,007 patients with TIA (mean age 73 years, 54% male), 1,110 pairs could be matched. Compared to management elsewhere in hospitals, management in an SU was associated with improved cumulative survival at 180 days post event (hazard ratio 0.57, 95% confidence interval 0.35-0.94; p = 0.029), despite not being statistically significant at 90 days (hazard ratio 0.66, 95% confidence interval 0.33-1.31; p = 0.237). Overall, there were no differences for being discharged on antihypertensive medication or with a care plan, and the 90- to 180-day self-reported outcomes between these groups were similar. In subgroup analyses of 461 matched pairs treated in hospitals in one Australian state (Queensland), patients treated in an SU were more often prescribed aspirin within 48 hours (73% vs 62%, p less than 0.001) and discharged on antithrombotic medications (84% vs 71%, p less than 0.001) than those not treated in an SU.

CONCLUSIONS: Hospitalized patients with TIA managed in SUs had better survival at 180 days than those treated in alternate wards, potentially through better management, but further research is needed.

B. Outcomes of Admitted vs. Discharged ED Patients with TIA

For patients who are discharged, outcomes are better when they are referred for follow-up specialty care.

Kapral MK, et al. Neurology 2016;86(17):1582-9.

OBJECTIVE: To evaluate the care and outcomes of patients with TIA or minor stroke admitted to the hospital vs discharged from the emergency department (ED).

METHODS: We used the Ontario Stroke Registry to create a cohort of patients with minor ischemic stroke/TIA who presented to the hospital April 1, 2008, to March 31, 2009, or April 1, 2010, to March 31, 2011, in the province of Ontario, Canada. We compared processes of care and outcomes (death or recurrent stroke/TIA) in patients admitted to the hospital and discharged with and without stroke prevention clinic follow-up.

RESULTS: In our sample of 8,540 patients, the use of recommended interventions was highest in admitted patients, followed by discharged patients referred to prevention clinics, followed by those discharged without clinic referral. Eight percent of nonadmitted patients returned to the hospital with recurrent stroke/TIA within 1 week of the index event. One-year stroke case-fatality was similar in admitted and discharged patients (adjusted hazard ratio 1.11; 95% confidence interval 0.92-1.34). Among patients discharged from EDs, referral to a stroke prevention clinic was associated with a markedly lower risk of mortality (adjusted hazard ratio 0.49; 95% confidence interval 0.38-0.64).

CONCLUSIONS: Patients with minor ischemic stroke or TIA discharged from the ED are less likely than admitted patients to receive timely stroke care interventions. Among discharged patients, referral to a stroke prevention clinic is associated with improved processes of care and lower mortality. Additional strategies are needed to improve access to high-quality outpatient TIA care.

23. Diagnostic Errors Related to Acute Abdominal Pain in the ED

Medford-Davis L, et al. Emerg Med J. 2016;33(4):253-259.

Objective Diagnostic errors in the emergency department (ED) are harmful and costly. We reviewed a selected high-risk cohort of patients presenting to the ED with abdominal pain to evaluate for possible diagnostic errors and associated process breakdowns.

Design We conducted a retrospective chart review of ED patients over 18 years at an urban academic hospital. A computerised 'trigger' algorithm identified patients possibly at high risk for diagnostic errors to facilitate selective record reviews. The trigger determined patients to be at high risk because they: (1) presented to the ED with abdominal pain, and were discharged home and (2) had a return ED visit within 10 days that led to a hospitalisation. Diagnostic errors were defined as missed opportunities to make a correct or timely diagnosis based on the evidence available during the first ED visit, regardless of patient harm, and included errors that involved both ED and non-ED providers. Errors were determined by two independent record reviewers followed by team consensus in cases of disagreement.

Results Diagnostic errors occurred in 35 of 100 high-risk cases. Over two-thirds had breakdowns involving the patient–provider encounter (most commonly history-taking or ordering additional tests) and/or follow-up and tracking of diagnostic information (most commonly follow-up of abnormal test results). The most frequently missed diagnoses were gallbladder pathology (n=10) and urinary infections (n=5).

Conclusions Diagnostic process breakdowns in ED patients with abdominal pain most commonly involved history-taking, ordering insufficient tests in the patient–provider encounter and problems with follow-up of abnormal test results.

Full-text (free p registration): http://www.medscape.com/viewarticle/860704

24. Micro Bits

A. Why You Can't Lose Weight on a Diet

By Sandra Aamodt. New York Times, May 8, 2016

The problem isn't willpower. It's neuroscience. You can't - and shouldn't - fight back.

Full-text (free): http://www.nytimes.com/2016/05/08/opinion/sunday/why-you-cant-lose-weight-on-a-diet.html

B. Adverse events associated with oral fluoroquinolone use

1. Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study

Conclusions: Contrary to previous reports, oral fluoroquinolone treatment was not associated with an increased risk of serious arrhythmia in the general adult populations of Denmark and Sweden. Given the statistical power of the study, even small increases in relative and absolute risk could be ruled out. Since ciprofloxacin was the most commonly used fluoroquinolone in our study, we cannot exclude that intraclass differences influence the risk of serious arrhythmia associated with other less frequently used fluoroquinolones.

Full-text: http://www.bmj.com/content/352/bmj.i843

2. Fluoroquinolones to carry updated warnings over risk of muscle, nerve injury

Manufacturers of fluoroquinolones are being required by the FDA to update their boxed warnings to state that risks associated with the antibiotic drugs, such as nerve and muscle damage, often outweigh their benefits when other treatment options are available. The antibiotics are intended for the treatment of uncomplicated urinary tract infections, sinusitis and bronchitis.

C. Dietary fats: a new look at old data challenges established wisdom

It is widely accepted that diets rich in polyunsaturated fats protect against heart disease. Recently, the Global Burden of Disease team reported that each year insufficient intake of omega-6 polyunsaturated fats, the most common subgroup of polyunsaturated fats, results in over 700 000 deaths from coronary heart disease.1 Or does it? A linked study by Ramsden and colleagues (doi:10.1136/bmj.i1246) adds to the doubts around the health benefits of replacing saturated fat with polyunsaturated fats.2

This new study re-examines recovered data from a double blind randomised controlled trial that took place 45 years ago. The Minnesota Coronary Experiment (MCE) followed 9423 participants from state mental hospitals and a nursing home for 4.5 years. The trial tested whether replacement of saturated fat with vegetable oil rich in linoleic acid (an omega-6 polyunsaturated fat) reduces the risk of coronary heart disease and death through a reduction in serum cholesterol concentration.

As expected, the diet enriched with linoleic acid lowered serum cholesterol concentration. But it did not reduce mortality: in fact participants in the intervention group had a higher mortality than controls. The pooled results of the MCE and four similar trials failed to find any reduction in mortality from coronary heart disease.3 4 5 6

These unexpected results proved difficult to stomach for researchers at the time. The trial ended in 1973, but it took until 1989 for the results to be published.7 The authors reported no differences between the treatment and control groups for cardiovascular events, cardiovascular deaths, or total mortality, but immediately added that “a favorable trend for all these end-points occurred in some younger age groups.” In contrast, Ramsden and colleagues now suggest the possibility of increased risk of death in older adults among the participants given more linoleic acid.2 The findings of the two teams of authors do not differ fundamentally, but their interpretation does.

In the past decade, old certainties regarding dietary fats have been questioned, and some have been abandoned. Last year, US dietary guidelines removed dietary cholesterol and total fat as risk factors worth worrying about.8 With these new findings,2 9 the recommendation to consume less than 10% of calories per day from saturated fats will be under increased scrutiny.10

How did researchers come to believe so firmly in the “diet-heart hypothesis,” which holds that eating foods high in cholesterol and saturated fat leads to heart disease?...

The rest of the essay: http://www.bmj.com/content/353/bmj.i1512

D. International Validity of the HOSPITAL Score to Predict 30-Day Potentially Avoidable Hospital Readmissions

Conclusions and Relevance  The HOSPITAL score identified patients at high risk of 30-day potentially avoidable readmission with moderately high discrimination and excellent calibration when applied to a large international multicenter cohort of medical patients. This score has the potential to easily identify patients in need of more intensive transitional care interventions to prevent avoidable hospital readmissions.

Link: http://archinte.jamanetwork.com/article.aspx?articleid=2498847

E. Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis: A Randomized Trial

Conclusion: Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis.

Abstract: http://annals.org/article.aspx?articleid=2522435

F. Gradual Versus Abrupt Smoking Cessation: A Randomized, Controlled Noninferiority Trial

Conclusion: Quitting smoking abruptly is more likely to lead to lasting abstinence than cutting down first, even for smokers who initially prefer to quit by gradual reduction.

 Abstract: http://annals.org/article.aspx?articleid=2501853

G. Mechanical Symptoms and Arthroscopic Partial Meniscectomy in Patients With Degenerative Meniscus Tear: A Secondary Analysis of a Randomized Trial

Conclusion: Resection of a torn meniscus has no added benefit over sham surgery to relieve knee catching or occasional locking. These findings question whether mechanical symptoms are caused by a degenerative meniscus tear and prompt caution in using patients' self-report of these symptoms as an indication for APM.

Abstract: http://annals.org/article.aspx?articleid=2490532

H. Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants

Conclusion: The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent.

Abstract: http://www.nejm.org/doi/full/10.1056/NEJMoa1514210

I. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years

Conclusions and Relevance  Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.

Full-text: http://jama.jamanetwork.com/article.aspx?articleid=2524266

J. Macrolide antibiotics and the risk of ventricular arrhythmia in older adults

Interpretation: Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated.

Full-text: http://www.cmaj.ca/content/188/7/E120.full

K. Physical activity may reduce risk of 13 cancers, study says

A study in JAMA Internal Medicine linked higher levels of physical activity to risk reductions of between 10% and 42% for 13 of 26 cancers examined. The data on more than 1.4 million people found the strongest connection for gastroesophageal and hematologic cancers, researchers said.

Abstract: http://archinte.jamanetwork.com/article.aspx?articleid=2521826

L. Swaddling tied to increased risk of SIDS

Swaddling infants may increase their risk of sudden infant death syndrome (SIDS) during sleep, an analysis of previous research suggests.

Overall, babies wrapped in light cloth or blankets, a practice known as swaddling, were about 38 percent more likely to die of SIDS than infants who didn’t get swaddled, researchers report in the journal Pediatrics.

Abstract: http://pediatrics.aappublications.org/content/early/2016/05/05/peds.2015-3275

M. When you take acetaminophen, you don't feel others' pain as much: The popular painkiller reduces empathy, study finds

Essay: https://www.sciencedaily.com/releases/2016/05/160510084257.htm

Mischkowski M, et al. From Painkiller to Empathy Killer: Acetaminophen (Paracetamol) Reduces Empathy for Pain. Social Cognitive and Affective Neuroscience, 2016; nsw057 DOI: 10.1093/scan/nsw057

Abstract: http://scan.oxfordjournals.org/content/early/2016/05/02/scan.nsw057.abstract