First Edition

CDC Issues New Opioid Prescribing Guideline

BY SHARON WORCESTER

Frontline Medical News

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released by the Centers for Disease Control and Prevention (CDC).

The 12 recommendations included in the guideline, which is available at http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1er.htm, center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the US government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr Tom Frieden, noted that “overprescribing opioids—largely for chronic pain—is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain—and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day)—died within 2.5 years of the first prescription.

Dr Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients—the vast majority of patients—the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services (HHS). A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and...death,” she said.

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers (PCPs)—who account for about half of all opioid prescriptions—a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacological therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

“In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain (available at http://stacks.cdc.gov/view/cdc/38025), and a Web site (http://www.cdc.gov/drugoverdose/prescribing/resources.html) with additional tools for implementing the recommendations within the guideline.

Patients of PCPs who follow these new guidelines and alter their opioid prescribing practices might subsequently present more frequently to the ED seeking opioid pain medications.

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. ePub: 15 March 2016. doi:http://dx.doi.org/10.15585/mmwr.rr6501e1er.

Legalization of Marijuana in Colorado Is Followed by an Increase in Marijuana-related ED Visits by Nonresidents

BY JEFF BAUER

FROM N ENGL J MED

"Marijuana tourism”—when individuals travel to a state where marijuana is legal for purpose of consuming the drug—may be responsible for a steep increase in marijuana-related visits by out-of-state residents observed at a Colorado ED from 2013 to 2014. Colorado legalized marijuana in 2012, and retail sales began in 2014.

Researchers looked at the rates of marijuana-related visits (determined by International Classification of Diseases, Ninth Revision codes) to the ED of a single urban academic hospital hospital in Aurora, CO from 2012 to 2014. Researchers compared the rate of such visits by Colorado residents versus out-of-state residents based on the ZIP code patients provided when they registered in the ED.

The rate of marijuana-related ED visits among out-of-state residents roughly doubled from 85 per 10,000 visits in 2013 to 168 per 10,000 visits in 2014. The rate of such visits among Colorado residents did not change significantly during that time: it was 106 per 10,000 visits in 2013 and 112 per 10,000 visits in 2014. From 2012 to 2013—before marijuana was legalized—the rate of marijuana-related ED visits did not change significantly among Colorado residents or out-of-state residents.

Statewide, according to data from the Colorado Hospital Association, the rate of marijuana-related ED visits by out-of-state residents increased from 112 per 10,000 visits in 2013 to 163 per 10,000 visits in 2014. Among Colorado residents, this rate increased from 86 per 10,000 visits in 2013 to 101 per 10,000 visits in 2014.

Kim HS, Hall KE, Genco EK, Van Dyke M, Barker E, Monte AA. Marijuana tourism and emergency department visits in Colorado. N Engl J Med. 2016;374(8):797-798. doi:10.1056/NEJMc1515009.

CDC Issues New Opioid Prescribing Guideline

BY SHARON WORCESTER

Frontline Medical News

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released by the Centers for Disease Control and Prevention (CDC).

The 12 recommendations included in the guideline, which is available at http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1er.htm, center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the US government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr Tom Frieden, noted that “overprescribing opioids—largely for chronic pain—is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain—and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day)—died within 2.5 years of the first prescription.

Dr Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients—the vast majority of patients—the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services (HHS). A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and...death,” she said.

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers (PCPs)—who account for about half of all opioid prescriptions—a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacological therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

“In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain (available at http://stacks.cdc.gov/view/cdc/38025), and a Web site (http://www.cdc.gov/drugoverdose/prescribing/resources.html) with additional tools for implementing the recommendations within the guideline.

Patients of PCPs who follow these new guidelines and alter their opioid prescribing practices might subsequently present more frequently to the ED seeking opioid pain medications.

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. ePub: 15 March 2016. doi:http://dx.doi.org/10.15585/mmwr.rr6501e1er.

Legalization of Marijuana in Colorado Is Followed by an Increase in Marijuana-related ED Visits by Nonresidents

BY JEFF BAUER

FROM N ENGL J MED

"Marijuana tourism”—when individuals travel to a state where marijuana is legal for purpose of consuming the drug—may be responsible for a steep increase in marijuana-related visits by out-of-state residents observed at a Colorado ED from 2013 to 2014. Colorado legalized marijuana in 2012, and retail sales began in 2014.

Researchers looked at the rates of marijuana-related visits (determined by International Classification of Diseases, Ninth Revision codes) to the ED of a single urban academic hospital hospital in Aurora, CO from 2012 to 2014. Researchers compared the rate of such visits by Colorado residents versus out-of-state residents based on the ZIP code patients provided when they registered in the ED.

The rate of marijuana-related ED visits among out-of-state residents roughly doubled from 85 per 10,000 visits in 2013 to 168 per 10,000 visits in 2014. The rate of such visits among Colorado residents did not change significantly during that time: it was 106 per 10,000 visits in 2013 and 112 per 10,000 visits in 2014. From 2012 to 2013—before marijuana was legalized—the rate of marijuana-related ED visits did not change significantly among Colorado residents or out-of-state residents.

Statewide, according to data from the Colorado Hospital Association, the rate of marijuana-related ED visits by out-of-state residents increased from 112 per 10,000 visits in 2013 to 163 per 10,000 visits in 2014. Among Colorado residents, this rate increased from 86 per 10,000 visits in 2013 to 101 per 10,000 visits in 2014.

Kim HS, Hall KE, Genco EK, Van Dyke M, Barker E, Monte AA. Marijuana tourism and emergency department visits in Colorado. N Engl J Med. 2016;374(8):797-798. doi:10.1056/NEJMc1515009.

CDC Issues New Opioid Prescribing Guideline

BY SHARON WORCESTER

Frontline Medical News

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released by the Centers for Disease Control and Prevention (CDC).

The 12 recommendations included in the guideline, which is available at http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1er.htm, center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the US government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr Tom Frieden, noted that “overprescribing opioids—largely for chronic pain—is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain—and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day)—died within 2.5 years of the first prescription.

Dr Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients—the vast majority of patients—the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services (HHS). A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and...death,” she said.

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers (PCPs)—who account for about half of all opioid prescriptions—a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacological therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

“In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain (available at http://stacks.cdc.gov/view/cdc/38025), and a Web site (http://www.cdc.gov/drugoverdose/prescribing/resources.html) with additional tools for implementing the recommendations within the guideline.

Patients of PCPs who follow these new guidelines and alter their opioid prescribing practices might subsequently present more frequently to the ED seeking opioid pain medications.

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. ePub: 15 March 2016. doi:http://dx.doi.org/10.15585/mmwr.rr6501e1er.

Legalization of Marijuana in Colorado Is Followed by an Increase in Marijuana-related ED Visits by Nonresidents

BY JEFF BAUER

FROM N ENGL J MED

"Marijuana tourism”—when individuals travel to a state where marijuana is legal for purpose of consuming the drug—may be responsible for a steep increase in marijuana-related visits by out-of-state residents observed at a Colorado ED from 2013 to 2014. Colorado legalized marijuana in 2012, and retail sales began in 2014.

Researchers looked at the rates of marijuana-related visits (determined by International Classification of Diseases, Ninth Revision codes) to the ED of a single urban academic hospital hospital in Aurora, CO from 2012 to 2014. Researchers compared the rate of such visits by Colorado residents versus out-of-state residents based on the ZIP code patients provided when they registered in the ED.

The rate of marijuana-related ED visits among out-of-state residents roughly doubled from 85 per 10,000 visits in 2013 to 168 per 10,000 visits in 2014. The rate of such visits among Colorado residents did not change significantly during that time: it was 106 per 10,000 visits in 2013 and 112 per 10,000 visits in 2014. From 2012 to 2013—before marijuana was legalized—the rate of marijuana-related ED visits did not change significantly among Colorado residents or out-of-state residents.

Statewide, according to data from the Colorado Hospital Association, the rate of marijuana-related ED visits by out-of-state residents increased from 112 per 10,000 visits in 2013 to 163 per 10,000 visits in 2014. Among Colorado residents, this rate increased from 86 per 10,000 visits in 2013 to 101 per 10,000 visits in 2014.

Kim HS, Hall KE, Genco EK, Van Dyke M, Barker E, Monte AA. Marijuana tourism and emergency department visits in Colorado. N Engl J Med. 2016;374(8):797-798. doi:10.1056/NEJMc1515009.

WHO Declares ‘Public Health Emergency’ for Microcephaly Linked to Zika Virus
BY MARY ELLEN SCHNEIDER
Frontline Medical News

The World Health Organization (WHO) has declared a “public health emergency of international concern” related to the clusters of microcephaly and other neurological complications reported in Brazil and earlier in French Polynesia. Though there is a strong association between these cases and the Zika virus, a causal link still has not been scientifically proven, according to the WHO.

The WHO’s emergency declaration clears the way for the international health community to move forward with a coordinated response. Dr Margaret Chan, WHO Director-General, said her organization plans to take a number of precautionary measures, including improving surveillance and detection of infections, congenital malformations, and neurological complications. They will also work with countries to intensify control of mosquito populations and help expedite the development of diagnostic tests and vaccines to protect at-risk populations.

The recommendations came after a February 1 meeting of the International Health Regulations Emergency Committee, which Dr Chan convened in response to the Zika virus outbreak and the observed increase in neurological disorders and neonatal malformations.

The group of 18 experts advised that the clusters of microcephaly and other complications constitute an “extraordinary event and a public health threat to other parts of the world.” The group did not recommend any restrictions on travel or trade with areas where the Zika virus transmission is ongoing, however.

“At present, the most important protective measures are the control of mosquito populations and the prevention of mosquito bites in at-risk individuals, especially pregnant women,” Dr Chan said during a press briefing.

Dr Chan said it’s unclear how long it will take to determine if Zika virus is causing the uptick in microcephaly and other congenital malformations and neurological abnormalities, but health officials are working to set up case-control studies. 

Preparing for Zika Virus Outbreaks

The recent spike in Zika virus cases in Central and South America brings with it the alarming risk— and even the expectation—of outbreaks occuring in the United States. How should US-based clinicians prepare for the inevitable?

“The current outbreaks of Zika virus are the first of their kind in the Americas, so there isn’t a previous history of Zika virus spreading into the [United States],” explained Dr Joy St. John, director of surveillance, disease prevention, and control at the Caribbean Public Health Agency in Trinidad.

But now that the virus has hit the United States, with a confirmed case in Texas and more emerging since then, Dr St. John said the most important thing is for US health care providers to recognize the signs and symptoms of Zika virus infection. Carried and transmitted by the Aedes aegypti species of mosquito, Zika virus symptoms are relatively mild, consisting predominantly of maculopapular rash, fever, arthralgia, myalgia, and conjunctivitis. Only one in five individuals with a Zika virus infection develop symptoms, but patients who present as such and who have traveled to Central or South America in the week prior to the onset of symptoms should be considered likely infected.

“At present, there is no rapid test available for diagnosis of Zika,” said Dr St. John. “Diagnosis is primarily based on detection of viral RNA from clinical serum specimens in acutely ill patients.”

To that end, polymerase chain reaction (PCR) testing can be conducted on serum samples collected within 3 to 5 days of symptom onset. Beyond that, elevated levels of immunoglobulin M antibodies can be confirmed by serology, based on the neutralization, seroconversion or four-fold increase of Zika-specific antibodies in paired samples. However, Dr St. John warned that “Due to the possibility of cross reactivity with other viruses, for example, dengue, it is strongly recommended samples be collected early enough for PCR testing.”

Zika and Pregnancy

Zika virus has now been identified in 14 countries and territories worldwide, and while most infected patients experience relatively mild symptoms, Zika becomes very concerning when it infects a pregnant woman, as there have been cases of microcephaly in children whose mothers were infected with Zika virus during pregnancy. Although the association of microcephaly with Zika virus infection during pregnancy has not been definitively confirmed, the Centers for Disease Control and Prevention (CDC) have already issued a warning to Americans—particularly pregnant women—about traveling to high-risk areas.

“Scientifically, we’re not 100% sure if Zika virus is causing microcephaly, [but] what we’re seeing is in certain Brazilian districts, there’s been a 20-fold increase in rates of microcephaly at the same time that there’s been a lot more Zika virus in pregnant women,” explained Dr Sanjaya Senanayake of Australian National University in Canberra.

According to data from the CDC, 1,248 suspected cases of microcephaly had been reported in Brazil as of November 28, 2015, compared to the annual rate of just 150 to 200 such cases during 2010 through 2014. “Examination of the fetus [and] amniotic fluid, in some cases, has shown Zika virus, so there seems to be an association,” Dr Senanayake clarified, adding that “the [ANVISA –  Brazilian Health Surveillance Agency] has told women in certain districts where there’s been a lot of microcephaly not to get pregnant.”

Brazil is set to host millions of guests from around the world as the 2016 Olympics get underway in only a few months’ time. Women who are pregnant or anticipate becoming pregnant should consider the risks if they are planning to travel to Rio de Janeiro. The risk of microcephaly does not apply to infected women who are not pregnant, however, as the CDC states that “Zika virus usually remains in the blood of an infected person for only a few days to a week,” and therefore “does not pose a risk of birth defects for future pregnancies.”

Dr St. Joy also stated that “public health personnel are still cautioning pregnant women to take special care to avoid mosquito bites during their pregnancies,” adding that the “[Pan-American Health Organization] is working on its guidelines for surveillance of congenital abnormalities.”

Clinical Insights

With treatment options so sparse—there is no vaccine or drug available specifically meant to combat a Zika virus infection—what can healthcare providers do for their patients? The CDC advises health care providers to “treat the symptoms,” which means telling patients to stay in bed, stay hydrated, and, most importantly, stay away from aspirins and NSAIDs “until dengue can be ruled out to reduce the risk of hemorrhage.” Acetaminophen or paracetamol are safe to use, in order to mitigate fever symptoms.

Those who are infected are also advised to stay indoors and remain as isolated as possible for at least a week after symptoms first present. While the risk of a domestic outbreak is probably low, Dr St. John said, the more exposure a Zika virus-infected individual has to the outside world, the more likely they are to be bitten by another mosquito, which can then carry and transmit the virus to another person.

“Chikungunya and dengue virus, which are transmitted by the same vectors [as Zika virus], have not managed to establish ongoing transmission in the United States despite repeated importations, [so] it is likely that Zika virus’ spread would follow a similar pattern,” Dr St. John noted.

Though rare, sexual transmission of Zika virus has also been found in at least one case, although it had been previously suspected for some time. In December 2013, a 44-year-old Tahitian man sought treatment for hematospermia. Analysis of his sperm, however, found Zika virus, indicating possible sexual transmission of the virus.

“The observation that [Zika virus] RNA was detectable in urine after viremia clearance in blood suggests that, as found for [dengue] and [West Nile virus] infections, urine samples can yield evidence of [Zika virus] for late diagnosis, but more investigation is needed,” the study concluded.

“The best way to control all this is to control the mosquito,” said Dr Senanayake. “You get a four-for-one deal; not only do you get rid of Zika virus, but also chikungunya, dengue, and yellow fever.” Dr Senanayake added that advanced research is currently underway in mosquito control efforts, including the idea of releasing mosquitoes into the wild that have been genetically modified so they cannot breed.

Now that the Illinois Department of Health has confirmed two new cases of Zika virus infection in that state, with other new cases cropping up in Saint Martin, Guadeloupe, and El Salvador, providers should remain vigilant, taking note of patients who have traveled to afflicted regions and show mosquito bites. Person-to-person transmission is “rare as hen’s teeth,” said Dr Senanayake, which is to say, it is highly unlikely to occur. Nonetheless, he said information and communication is the best way to ensure that Zika virus does not spread widely in the United States.

Study Characterizes Intracerebral Hemorrhage With New Oral Anticoagulants
BY MARY ANN MOON
FROM JAMA NEUROLOGY

Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants carries a high mortality and frequently involves hematoma expansion, according to a report published online December 14 in JAMA Neurology.¹

The characteristics and natural history of acute-phase non–vitamin-K antagonist oral anticoagulant (NOAC)-associated intracerebral hemorrhage “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate in this patient population, said Dr Jan C. Purrucker of the department of neurology at Heidelberg (Germany) University and his associates.¹

Dr Purrucker and his associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA), a prospective registry with certified stroke units in Germany. For their substudy, the investigators focused on 61 adults with a mean age of 76 years (range, 46-97 years) who were taking novel anticoagulants (NOACs; [apixaban, dabigatran etexilate, or rivaroxaban]) and had moderate to severe neurologic deficits and a median hematoma volume of 10.8 mL at presentation. Prothrombin complex concentrate was given to 35 (57%).

Mortality was high; 10 (16%) patients died during the acute inpatient stay and 17 (28%) at 3 months. Of the survivors, 65% had an unfavorable outcome. Substantial hematoma expansion—defined as a 33% or greater relative increase or 6 mL or greater absolute increase in intracerebral hemorrhage volume—affected 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36%-56%) and is higher, compared with that related to intracerebral hemorrhage in patients not receiving anticoagulation (12%-26%),” the researchers wrote.

Both larger hematoma volume at baseline (odds ratio [OR], 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin-complex concentrate failed to limit lesion expansion or avert adverse outcomes. This might be because patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who were not given prothrombin complex concentrate. In any case, “our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin-complex concentrate treatment and outcome,” they noted.

FDA Approves Treatment for Chemotherapy, Overdoses, Life-threatening Toxicities
BY ELIZABETH MECHCATIE
Frontline Medical News

Uridine triacetate, a pyrimidine analogue, has been approved for the emergency treatment of fluorouracil or capecitabine overdoses in adults and children, and for patients who develop “certain severe or life-threatening toxicities within 4 days of receiving” these treatments, the Food and Drug Administration (FDA) announced on December 11, 2015.

“Today’s approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents,” Dr Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement.¹ It will be marketed as Vistogard by Wellstat Therapeutics.

Uridine comes in an oral granule formulation that can be mixed into soft foods or, when necessary, administered via a nasogastric or gastrostomy tube, the prescribing information states. The indication is for use after an overdose “regardless of the presence of symptoms,” and for treating “early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (eg, gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration,” according to the prescribing information.

Uridine blocks cell damage and cell death caused by fluorouracil chemotherapy, according to the statement.

Uridine was evaluated in two studies of 135 adults and children with cancer treated for a fluorouracil or capecitabine overdose or for early-onset severe or life-threatening toxicities within 96 hours after receiving fluorouracil. Among those treated for an overdose, 97% were alive 30 days after treatment, and among those treated for early-onset severe or life-threatening toxicity, 89% were alive 30 days after treatment. In addition, 33% of the patients resumed chemotherapy within 30 days, according to the FDA statement. Diarrhea, vomiting, and nausea were the most common adverse events associated with treatment.

FDA Advisory Committees Support Changing Codeine Contraindications for Children
BY DEEPAK CHITNIS
AT AN FDA ADVISORY COMMITTEE MEETING

SILVER SPRING, MD—Food and Drug Administration  advisory committees have voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years. 

Twenty members of the FDA’s Pulmonary-Allergy Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted on December 10 for the contraindication. Six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. One committee member voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. One member supported removing codeine from the monograph only for children under age 2 years.

The decision to vote on approving amendments to the contraindications for codeine use—which would affect not just the monogram, but labeling as well—comes on the heels of the FDA announcing last summer that they would be investigating the safety of codeine-containing drugs in children.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr Sally Seymour, the FDA’s Deputy Director for Safety.

The FDA is not required to follow the advice of its advisory panels. No members of the panel reported any relevant financial conflicts of interest.

80% of Emergency Physicians Say Mental Health Crisis Response Needs Overhaul
BY WHITNEY MCKNIGHT
Frontline Medical News

Emergency medicine professionals have teamed up with mental health workers and patient advocates to call for a new model of care for ED patients in mental health crisis.

The Coalition on Psychiatric Emergencies,” is focused on improving the delivery of emergency psychiatric care, and is supported by more than 30 national emergency medicine, mental health, and patient advocate groups, including the ACEP, the American Psychiatric Association, and the National Alliance on Mental Illness (NAMI). The action comes on the heels of a survey that found 80% of 1,500 US EPs think the system for treating people in acute mental health crisis is broken.

“It’s time we think about doing things differently,” Dr Michael Gerardi, COPE Steering Committee Chair and immediate past president of ACEP, said in a statement. “Through this unique collaboration, the Coalition on Psychiatric Emergencies will focus on developing a more unified treatment model and improving the treatment experience for both patients and health care providers. We want to provide the best care for all our patients and reduce health care costs.”

Among its several goals, the coalition seeks to shorten the time between when a person in mental health crisis presents to the ED and is admitted to an inpatient psychiatric bed. In a recent NAMI survey of 1,400 families, 38% waited more than 7 hours in the ED before seeing a mental health professional. For 21% of those families, the wait was more than 10 hours.

The Coalition on Psychiatric Emergencies also seeks adequate education and training for all emergency personnel who care for patients experiencing psychiatric emergencies.

“Emergency department staff need proper training not only on how to handle behavioral health emergencies, but also on how to initiate care for patients who may remain in the ED setting for long periods of time,” Dr Lorenzo Norris, director of inpatient psychiatric services at George Washington University Hospital in Washington, DC, said in an interview. “Establishing these new systems will likely require robust funding efforts.”

‘‘There is a growing need for change. At our hospital, we have definitely seen an uptick in the number of patients seeking emergency psychiatric care,” Dr Norris said. “Our approach has been to hire a clinician whose sole duty is to work collaboratively with patients and ED staff. It’s the first step in our ultimate goal of creating an ED behavioral health team that includes a psychiatrist, an emergency physician, nursing staff, social worker, and others who can provide the patient with comprehensive care at the initial point of contact.”

Currently in the United States, there are no standard protocols for a psychiatric emergency, according to the National Institute of Mental Health. The online survey was conducted within the ACEP membership between July 1 through 31, 2015. The response rate was 6% and the margin of error of 2.5%.

WHO Declares ‘Public Health Emergency’ for Microcephaly Linked to Zika Virus
BY MARY ELLEN SCHNEIDER
Frontline Medical News

The World Health Organization (WHO) has declared a “public health emergency of international concern” related to the clusters of microcephaly and other neurological complications reported in Brazil and earlier in French Polynesia. Though there is a strong association between these cases and the Zika virus, a causal link still has not been scientifically proven, according to the WHO.

The WHO’s emergency declaration clears the way for the international health community to move forward with a coordinated response. Dr Margaret Chan, WHO Director-General, said her organization plans to take a number of precautionary measures, including improving surveillance and detection of infections, congenital malformations, and neurological complications. They will also work with countries to intensify control of mosquito populations and help expedite the development of diagnostic tests and vaccines to protect at-risk populations.

The recommendations came after a February 1 meeting of the International Health Regulations Emergency Committee, which Dr Chan convened in response to the Zika virus outbreak and the observed increase in neurological disorders and neonatal malformations.

The group of 18 experts advised that the clusters of microcephaly and other complications constitute an “extraordinary event and a public health threat to other parts of the world.” The group did not recommend any restrictions on travel or trade with areas where the Zika virus transmission is ongoing, however.

“At present, the most important protective measures are the control of mosquito populations and the prevention of mosquito bites in at-risk individuals, especially pregnant women,” Dr Chan said during a press briefing.

Dr Chan said it’s unclear how long it will take to determine if Zika virus is causing the uptick in microcephaly and other congenital malformations and neurological abnormalities, but health officials are working to set up case-control studies. 

Preparing for Zika Virus Outbreaks

The recent spike in Zika virus cases in Central and South America brings with it the alarming risk— and even the expectation—of outbreaks occuring in the United States. How should US-based clinicians prepare for the inevitable?

“The current outbreaks of Zika virus are the first of their kind in the Americas, so there isn’t a previous history of Zika virus spreading into the [United States],” explained Dr Joy St. John, director of surveillance, disease prevention, and control at the Caribbean Public Health Agency in Trinidad.

But now that the virus has hit the United States, with a confirmed case in Texas and more emerging since then, Dr St. John said the most important thing is for US health care providers to recognize the signs and symptoms of Zika virus infection. Carried and transmitted by the Aedes aegypti species of mosquito, Zika virus symptoms are relatively mild, consisting predominantly of maculopapular rash, fever, arthralgia, myalgia, and conjunctivitis. Only one in five individuals with a Zika virus infection develop symptoms, but patients who present as such and who have traveled to Central or South America in the week prior to the onset of symptoms should be considered likely infected.

“At present, there is no rapid test available for diagnosis of Zika,” said Dr St. John. “Diagnosis is primarily based on detection of viral RNA from clinical serum specimens in acutely ill patients.”

To that end, polymerase chain reaction (PCR) testing can be conducted on serum samples collected within 3 to 5 days of symptom onset. Beyond that, elevated levels of immunoglobulin M antibodies can be confirmed by serology, based on the neutralization, seroconversion or four-fold increase of Zika-specific antibodies in paired samples. However, Dr St. John warned that “Due to the possibility of cross reactivity with other viruses, for example, dengue, it is strongly recommended samples be collected early enough for PCR testing.”

Zika and Pregnancy

Zika virus has now been identified in 14 countries and territories worldwide, and while most infected patients experience relatively mild symptoms, Zika becomes very concerning when it infects a pregnant woman, as there have been cases of microcephaly in children whose mothers were infected with Zika virus during pregnancy. Although the association of microcephaly with Zika virus infection during pregnancy has not been definitively confirmed, the Centers for Disease Control and Prevention (CDC) have already issued a warning to Americans—particularly pregnant women—about traveling to high-risk areas.

“Scientifically, we’re not 100% sure if Zika virus is causing microcephaly, [but] what we’re seeing is in certain Brazilian districts, there’s been a 20-fold increase in rates of microcephaly at the same time that there’s been a lot more Zika virus in pregnant women,” explained Dr Sanjaya Senanayake of Australian National University in Canberra.

According to data from the CDC, 1,248 suspected cases of microcephaly had been reported in Brazil as of November 28, 2015, compared to the annual rate of just 150 to 200 such cases during 2010 through 2014. “Examination of the fetus [and] amniotic fluid, in some cases, has shown Zika virus, so there seems to be an association,” Dr Senanayake clarified, adding that “the [ANVISA –  Brazilian Health Surveillance Agency] has told women in certain districts where there’s been a lot of microcephaly not to get pregnant.”

Brazil is set to host millions of guests from around the world as the 2016 Olympics get underway in only a few months’ time. Women who are pregnant or anticipate becoming pregnant should consider the risks if they are planning to travel to Rio de Janeiro. The risk of microcephaly does not apply to infected women who are not pregnant, however, as the CDC states that “Zika virus usually remains in the blood of an infected person for only a few days to a week,” and therefore “does not pose a risk of birth defects for future pregnancies.”

Dr St. Joy also stated that “public health personnel are still cautioning pregnant women to take special care to avoid mosquito bites during their pregnancies,” adding that the “[Pan-American Health Organization] is working on its guidelines for surveillance of congenital abnormalities.”

Clinical Insights

With treatment options so sparse—there is no vaccine or drug available specifically meant to combat a Zika virus infection—what can healthcare providers do for their patients? The CDC advises health care providers to “treat the symptoms,” which means telling patients to stay in bed, stay hydrated, and, most importantly, stay away from aspirins and NSAIDs “until dengue can be ruled out to reduce the risk of hemorrhage.” Acetaminophen or paracetamol are safe to use, in order to mitigate fever symptoms.

Those who are infected are also advised to stay indoors and remain as isolated as possible for at least a week after symptoms first present. While the risk of a domestic outbreak is probably low, Dr St. John said, the more exposure a Zika virus-infected individual has to the outside world, the more likely they are to be bitten by another mosquito, which can then carry and transmit the virus to another person.

“Chikungunya and dengue virus, which are transmitted by the same vectors [as Zika virus], have not managed to establish ongoing transmission in the United States despite repeated importations, [so] it is likely that Zika virus’ spread would follow a similar pattern,” Dr St. John noted.

Though rare, sexual transmission of Zika virus has also been found in at least one case, although it had been previously suspected for some time. In December 2013, a 44-year-old Tahitian man sought treatment for hematospermia. Analysis of his sperm, however, found Zika virus, indicating possible sexual transmission of the virus.

“The observation that [Zika virus] RNA was detectable in urine after viremia clearance in blood suggests that, as found for [dengue] and [West Nile virus] infections, urine samples can yield evidence of [Zika virus] for late diagnosis, but more investigation is needed,” the study concluded.

“The best way to control all this is to control the mosquito,” said Dr Senanayake. “You get a four-for-one deal; not only do you get rid of Zika virus, but also chikungunya, dengue, and yellow fever.” Dr Senanayake added that advanced research is currently underway in mosquito control efforts, including the idea of releasing mosquitoes into the wild that have been genetically modified so they cannot breed.

Now that the Illinois Department of Health has confirmed two new cases of Zika virus infection in that state, with other new cases cropping up in Saint Martin, Guadeloupe, and El Salvador, providers should remain vigilant, taking note of patients who have traveled to afflicted regions and show mosquito bites. Person-to-person transmission is “rare as hen’s teeth,” said Dr Senanayake, which is to say, it is highly unlikely to occur. Nonetheless, he said information and communication is the best way to ensure that Zika virus does not spread widely in the United States.

Study Characterizes Intracerebral Hemorrhage With New Oral Anticoagulants
BY MARY ANN MOON
FROM JAMA NEUROLOGY

Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants carries a high mortality and frequently involves hematoma expansion, according to a report published online December 14 in JAMA Neurology.¹

The characteristics and natural history of acute-phase non–vitamin-K antagonist oral anticoagulant (NOAC)-associated intracerebral hemorrhage “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate in this patient population, said Dr Jan C. Purrucker of the department of neurology at Heidelberg (Germany) University and his associates.¹

Dr Purrucker and his associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA), a prospective registry with certified stroke units in Germany. For their substudy, the investigators focused on 61 adults with a mean age of 76 years (range, 46-97 years) who were taking novel anticoagulants (NOACs; [apixaban, dabigatran etexilate, or rivaroxaban]) and had moderate to severe neurologic deficits and a median hematoma volume of 10.8 mL at presentation. Prothrombin complex concentrate was given to 35 (57%).

Mortality was high; 10 (16%) patients died during the acute inpatient stay and 17 (28%) at 3 months. Of the survivors, 65% had an unfavorable outcome. Substantial hematoma expansion—defined as a 33% or greater relative increase or 6 mL or greater absolute increase in intracerebral hemorrhage volume—affected 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36%-56%) and is higher, compared with that related to intracerebral hemorrhage in patients not receiving anticoagulation (12%-26%),” the researchers wrote.

Both larger hematoma volume at baseline (odds ratio [OR], 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin-complex concentrate failed to limit lesion expansion or avert adverse outcomes. This might be because patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who were not given prothrombin complex concentrate. In any case, “our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin-complex concentrate treatment and outcome,” they noted.

FDA Approves Treatment for Chemotherapy, Overdoses, Life-threatening Toxicities
BY ELIZABETH MECHCATIE
Frontline Medical News

Uridine triacetate, a pyrimidine analogue, has been approved for the emergency treatment of fluorouracil or capecitabine overdoses in adults and children, and for patients who develop “certain severe or life-threatening toxicities within 4 days of receiving” these treatments, the Food and Drug Administration (FDA) announced on December 11, 2015.

“Today’s approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents,” Dr Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement.¹ It will be marketed as Vistogard by Wellstat Therapeutics.

Uridine comes in an oral granule formulation that can be mixed into soft foods or, when necessary, administered via a nasogastric or gastrostomy tube, the prescribing information states. The indication is for use after an overdose “regardless of the presence of symptoms,” and for treating “early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (eg, gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration,” according to the prescribing information.

Uridine blocks cell damage and cell death caused by fluorouracil chemotherapy, according to the statement.

Uridine was evaluated in two studies of 135 adults and children with cancer treated for a fluorouracil or capecitabine overdose or for early-onset severe or life-threatening toxicities within 96 hours after receiving fluorouracil. Among those treated for an overdose, 97% were alive 30 days after treatment, and among those treated for early-onset severe or life-threatening toxicity, 89% were alive 30 days after treatment. In addition, 33% of the patients resumed chemotherapy within 30 days, according to the FDA statement. Diarrhea, vomiting, and nausea were the most common adverse events associated with treatment.

FDA Advisory Committees Support Changing Codeine Contraindications for Children
BY DEEPAK CHITNIS
AT AN FDA ADVISORY COMMITTEE MEETING

SILVER SPRING, MD—Food and Drug Administration  advisory committees have voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years. 

Twenty members of the FDA’s Pulmonary-Allergy Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted on December 10 for the contraindication. Six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. One committee member voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. One member supported removing codeine from the monograph only for children under age 2 years.

The decision to vote on approving amendments to the contraindications for codeine use—which would affect not just the monogram, but labeling as well—comes on the heels of the FDA announcing last summer that they would be investigating the safety of codeine-containing drugs in children.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr Sally Seymour, the FDA’s Deputy Director for Safety.

The FDA is not required to follow the advice of its advisory panels. No members of the panel reported any relevant financial conflicts of interest.

80% of Emergency Physicians Say Mental Health Crisis Response Needs Overhaul
BY WHITNEY MCKNIGHT
Frontline Medical News

Emergency medicine professionals have teamed up with mental health workers and patient advocates to call for a new model of care for ED patients in mental health crisis.

The Coalition on Psychiatric Emergencies,” is focused on improving the delivery of emergency psychiatric care, and is supported by more than 30 national emergency medicine, mental health, and patient advocate groups, including the ACEP, the American Psychiatric Association, and the National Alliance on Mental Illness (NAMI). The action comes on the heels of a survey that found 80% of 1,500 US EPs think the system for treating people in acute mental health crisis is broken.

“It’s time we think about doing things differently,” Dr Michael Gerardi, COPE Steering Committee Chair and immediate past president of ACEP, said in a statement. “Through this unique collaboration, the Coalition on Psychiatric Emergencies will focus on developing a more unified treatment model and improving the treatment experience for both patients and health care providers. We want to provide the best care for all our patients and reduce health care costs.”

Among its several goals, the coalition seeks to shorten the time between when a person in mental health crisis presents to the ED and is admitted to an inpatient psychiatric bed. In a recent NAMI survey of 1,400 families, 38% waited more than 7 hours in the ED before seeing a mental health professional. For 21% of those families, the wait was more than 10 hours.

The Coalition on Psychiatric Emergencies also seeks adequate education and training for all emergency personnel who care for patients experiencing psychiatric emergencies.

“Emergency department staff need proper training not only on how to handle behavioral health emergencies, but also on how to initiate care for patients who may remain in the ED setting for long periods of time,” Dr Lorenzo Norris, director of inpatient psychiatric services at George Washington University Hospital in Washington, DC, said in an interview. “Establishing these new systems will likely require robust funding efforts.”

‘‘There is a growing need for change. At our hospital, we have definitely seen an uptick in the number of patients seeking emergency psychiatric care,” Dr Norris said. “Our approach has been to hire a clinician whose sole duty is to work collaboratively with patients and ED staff. It’s the first step in our ultimate goal of creating an ED behavioral health team that includes a psychiatrist, an emergency physician, nursing staff, social worker, and others who can provide the patient with comprehensive care at the initial point of contact.”

Currently in the United States, there are no standard protocols for a psychiatric emergency, according to the National Institute of Mental Health. The online survey was conducted within the ACEP membership between July 1 through 31, 2015. The response rate was 6% and the margin of error of 2.5%.

WHO Declares ‘Public Health Emergency’ for Microcephaly Linked to Zika Virus
BY MARY ELLEN SCHNEIDER
Frontline Medical News

The World Health Organization (WHO) has declared a “public health emergency of international concern” related to the clusters of microcephaly and other neurological complications reported in Brazil and earlier in French Polynesia. Though there is a strong association between these cases and the Zika virus, a causal link still has not been scientifically proven, according to the WHO.

The WHO’s emergency declaration clears the way for the international health community to move forward with a coordinated response. Dr Margaret Chan, WHO Director-General, said her organization plans to take a number of precautionary measures, including improving surveillance and detection of infections, congenital malformations, and neurological complications. They will also work with countries to intensify control of mosquito populations and help expedite the development of diagnostic tests and vaccines to protect at-risk populations.

The recommendations came after a February 1 meeting of the International Health Regulations Emergency Committee, which Dr Chan convened in response to the Zika virus outbreak and the observed increase in neurological disorders and neonatal malformations.

The group of 18 experts advised that the clusters of microcephaly and other complications constitute an “extraordinary event and a public health threat to other parts of the world.” The group did not recommend any restrictions on travel or trade with areas where the Zika virus transmission is ongoing, however.

“At present, the most important protective measures are the control of mosquito populations and the prevention of mosquito bites in at-risk individuals, especially pregnant women,” Dr Chan said during a press briefing.

Dr Chan said it’s unclear how long it will take to determine if Zika virus is causing the uptick in microcephaly and other congenital malformations and neurological abnormalities, but health officials are working to set up case-control studies. 

Preparing for Zika Virus Outbreaks

The recent spike in Zika virus cases in Central and South America brings with it the alarming risk— and even the expectation—of outbreaks occuring in the United States. How should US-based clinicians prepare for the inevitable?

“The current outbreaks of Zika virus are the first of their kind in the Americas, so there isn’t a previous history of Zika virus spreading into the [United States],” explained Dr Joy St. John, director of surveillance, disease prevention, and control at the Caribbean Public Health Agency in Trinidad.

But now that the virus has hit the United States, with a confirmed case in Texas and more emerging since then, Dr St. John said the most important thing is for US health care providers to recognize the signs and symptoms of Zika virus infection. Carried and transmitted by the Aedes aegypti species of mosquito, Zika virus symptoms are relatively mild, consisting predominantly of maculopapular rash, fever, arthralgia, myalgia, and conjunctivitis. Only one in five individuals with a Zika virus infection develop symptoms, but patients who present as such and who have traveled to Central or South America in the week prior to the onset of symptoms should be considered likely infected.

“At present, there is no rapid test available for diagnosis of Zika,” said Dr St. John. “Diagnosis is primarily based on detection of viral RNA from clinical serum specimens in acutely ill patients.”

To that end, polymerase chain reaction (PCR) testing can be conducted on serum samples collected within 3 to 5 days of symptom onset. Beyond that, elevated levels of immunoglobulin M antibodies can be confirmed by serology, based on the neutralization, seroconversion or four-fold increase of Zika-specific antibodies in paired samples. However, Dr St. John warned that “Due to the possibility of cross reactivity with other viruses, for example, dengue, it is strongly recommended samples be collected early enough for PCR testing.”

Zika and Pregnancy

Zika virus has now been identified in 14 countries and territories worldwide, and while most infected patients experience relatively mild symptoms, Zika becomes very concerning when it infects a pregnant woman, as there have been cases of microcephaly in children whose mothers were infected with Zika virus during pregnancy. Although the association of microcephaly with Zika virus infection during pregnancy has not been definitively confirmed, the Centers for Disease Control and Prevention (CDC) have already issued a warning to Americans—particularly pregnant women—about traveling to high-risk areas.

“Scientifically, we’re not 100% sure if Zika virus is causing microcephaly, [but] what we’re seeing is in certain Brazilian districts, there’s been a 20-fold increase in rates of microcephaly at the same time that there’s been a lot more Zika virus in pregnant women,” explained Dr Sanjaya Senanayake of Australian National University in Canberra.

According to data from the CDC, 1,248 suspected cases of microcephaly had been reported in Brazil as of November 28, 2015, compared to the annual rate of just 150 to 200 such cases during 2010 through 2014. “Examination of the fetus [and] amniotic fluid, in some cases, has shown Zika virus, so there seems to be an association,” Dr Senanayake clarified, adding that “the [ANVISA –  Brazilian Health Surveillance Agency] has told women in certain districts where there’s been a lot of microcephaly not to get pregnant.”

Brazil is set to host millions of guests from around the world as the 2016 Olympics get underway in only a few months’ time. Women who are pregnant or anticipate becoming pregnant should consider the risks if they are planning to travel to Rio de Janeiro. The risk of microcephaly does not apply to infected women who are not pregnant, however, as the CDC states that “Zika virus usually remains in the blood of an infected person for only a few days to a week,” and therefore “does not pose a risk of birth defects for future pregnancies.”

Dr St. Joy also stated that “public health personnel are still cautioning pregnant women to take special care to avoid mosquito bites during their pregnancies,” adding that the “[Pan-American Health Organization] is working on its guidelines for surveillance of congenital abnormalities.”

Clinical Insights

With treatment options so sparse—there is no vaccine or drug available specifically meant to combat a Zika virus infection—what can healthcare providers do for their patients? The CDC advises health care providers to “treat the symptoms,” which means telling patients to stay in bed, stay hydrated, and, most importantly, stay away from aspirins and NSAIDs “until dengue can be ruled out to reduce the risk of hemorrhage.” Acetaminophen or paracetamol are safe to use, in order to mitigate fever symptoms.

Those who are infected are also advised to stay indoors and remain as isolated as possible for at least a week after symptoms first present. While the risk of a domestic outbreak is probably low, Dr St. John said, the more exposure a Zika virus-infected individual has to the outside world, the more likely they are to be bitten by another mosquito, which can then carry and transmit the virus to another person.

“Chikungunya and dengue virus, which are transmitted by the same vectors [as Zika virus], have not managed to establish ongoing transmission in the United States despite repeated importations, [so] it is likely that Zika virus’ spread would follow a similar pattern,” Dr St. John noted.

Though rare, sexual transmission of Zika virus has also been found in at least one case, although it had been previously suspected for some time. In December 2013, a 44-year-old Tahitian man sought treatment for hematospermia. Analysis of his sperm, however, found Zika virus, indicating possible sexual transmission of the virus.

“The observation that [Zika virus] RNA was detectable in urine after viremia clearance in blood suggests that, as found for [dengue] and [West Nile virus] infections, urine samples can yield evidence of [Zika virus] for late diagnosis, but more investigation is needed,” the study concluded.

“The best way to control all this is to control the mosquito,” said Dr Senanayake. “You get a four-for-one deal; not only do you get rid of Zika virus, but also chikungunya, dengue, and yellow fever.” Dr Senanayake added that advanced research is currently underway in mosquito control efforts, including the idea of releasing mosquitoes into the wild that have been genetically modified so they cannot breed.

Now that the Illinois Department of Health has confirmed two new cases of Zika virus infection in that state, with other new cases cropping up in Saint Martin, Guadeloupe, and El Salvador, providers should remain vigilant, taking note of patients who have traveled to afflicted regions and show mosquito bites. Person-to-person transmission is “rare as hen’s teeth,” said Dr Senanayake, which is to say, it is highly unlikely to occur. Nonetheless, he said information and communication is the best way to ensure that Zika virus does not spread widely in the United States.

Study Characterizes Intracerebral Hemorrhage With New Oral Anticoagulants
BY MARY ANN MOON
FROM JAMA NEUROLOGY

Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants carries a high mortality and frequently involves hematoma expansion, according to a report published online December 14 in JAMA Neurology.¹

The characteristics and natural history of acute-phase non–vitamin-K antagonist oral anticoagulant (NOAC)-associated intracerebral hemorrhage “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate in this patient population, said Dr Jan C. Purrucker of the department of neurology at Heidelberg (Germany) University and his associates.¹

Dr Purrucker and his associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA), a prospective registry with certified stroke units in Germany. For their substudy, the investigators focused on 61 adults with a mean age of 76 years (range, 46-97 years) who were taking novel anticoagulants (NOACs; [apixaban, dabigatran etexilate, or rivaroxaban]) and had moderate to severe neurologic deficits and a median hematoma volume of 10.8 mL at presentation. Prothrombin complex concentrate was given to 35 (57%).

Mortality was high; 10 (16%) patients died during the acute inpatient stay and 17 (28%) at 3 months. Of the survivors, 65% had an unfavorable outcome. Substantial hematoma expansion—defined as a 33% or greater relative increase or 6 mL or greater absolute increase in intracerebral hemorrhage volume—affected 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36%-56%) and is higher, compared with that related to intracerebral hemorrhage in patients not receiving anticoagulation (12%-26%),” the researchers wrote.

Both larger hematoma volume at baseline (odds ratio [OR], 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin-complex concentrate failed to limit lesion expansion or avert adverse outcomes. This might be because patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who were not given prothrombin complex concentrate. In any case, “our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin-complex concentrate treatment and outcome,” they noted.

FDA Approves Treatment for Chemotherapy, Overdoses, Life-threatening Toxicities
BY ELIZABETH MECHCATIE
Frontline Medical News

Uridine triacetate, a pyrimidine analogue, has been approved for the emergency treatment of fluorouracil or capecitabine overdoses in adults and children, and for patients who develop “certain severe or life-threatening toxicities within 4 days of receiving” these treatments, the Food and Drug Administration (FDA) announced on December 11, 2015.

“Today’s approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents,” Dr Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement.¹ It will be marketed as Vistogard by Wellstat Therapeutics.

Uridine comes in an oral granule formulation that can be mixed into soft foods or, when necessary, administered via a nasogastric or gastrostomy tube, the prescribing information states. The indication is for use after an overdose “regardless of the presence of symptoms,” and for treating “early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (eg, gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration,” according to the prescribing information.

Uridine blocks cell damage and cell death caused by fluorouracil chemotherapy, according to the statement.

Uridine was evaluated in two studies of 135 adults and children with cancer treated for a fluorouracil or capecitabine overdose or for early-onset severe or life-threatening toxicities within 96 hours after receiving fluorouracil. Among those treated for an overdose, 97% were alive 30 days after treatment, and among those treated for early-onset severe or life-threatening toxicity, 89% were alive 30 days after treatment. In addition, 33% of the patients resumed chemotherapy within 30 days, according to the FDA statement. Diarrhea, vomiting, and nausea were the most common adverse events associated with treatment.

FDA Advisory Committees Support Changing Codeine Contraindications for Children
BY DEEPAK CHITNIS
AT AN FDA ADVISORY COMMITTEE MEETING

SILVER SPRING, MD—Food and Drug Administration  advisory committees have voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years. 

Twenty members of the FDA’s Pulmonary-Allergy Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted on December 10 for the contraindication. Six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. One committee member voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. One member supported removing codeine from the monograph only for children under age 2 years.

The decision to vote on approving amendments to the contraindications for codeine use—which would affect not just the monogram, but labeling as well—comes on the heels of the FDA announcing last summer that they would be investigating the safety of codeine-containing drugs in children.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr Sally Seymour, the FDA’s Deputy Director for Safety.

The FDA is not required to follow the advice of its advisory panels. No members of the panel reported any relevant financial conflicts of interest.

80% of Emergency Physicians Say Mental Health Crisis Response Needs Overhaul
BY WHITNEY MCKNIGHT
Frontline Medical News

Emergency medicine professionals have teamed up with mental health workers and patient advocates to call for a new model of care for ED patients in mental health crisis.

The Coalition on Psychiatric Emergencies,” is focused on improving the delivery of emergency psychiatric care, and is supported by more than 30 national emergency medicine, mental health, and patient advocate groups, including the ACEP, the American Psychiatric Association, and the National Alliance on Mental Illness (NAMI). The action comes on the heels of a survey that found 80% of 1,500 US EPs think the system for treating people in acute mental health crisis is broken.

“It’s time we think about doing things differently,” Dr Michael Gerardi, COPE Steering Committee Chair and immediate past president of ACEP, said in a statement. “Through this unique collaboration, the Coalition on Psychiatric Emergencies will focus on developing a more unified treatment model and improving the treatment experience for both patients and health care providers. We want to provide the best care for all our patients and reduce health care costs.”

Among its several goals, the coalition seeks to shorten the time between when a person in mental health crisis presents to the ED and is admitted to an inpatient psychiatric bed. In a recent NAMI survey of 1,400 families, 38% waited more than 7 hours in the ED before seeing a mental health professional. For 21% of those families, the wait was more than 10 hours.

The Coalition on Psychiatric Emergencies also seeks adequate education and training for all emergency personnel who care for patients experiencing psychiatric emergencies.

“Emergency department staff need proper training not only on how to handle behavioral health emergencies, but also on how to initiate care for patients who may remain in the ED setting for long periods of time,” Dr Lorenzo Norris, director of inpatient psychiatric services at George Washington University Hospital in Washington, DC, said in an interview. “Establishing these new systems will likely require robust funding efforts.”

‘‘There is a growing need for change. At our hospital, we have definitely seen an uptick in the number of patients seeking emergency psychiatric care,” Dr Norris said. “Our approach has been to hire a clinician whose sole duty is to work collaboratively with patients and ED staff. It’s the first step in our ultimate goal of creating an ED behavioral health team that includes a psychiatrist, an emergency physician, nursing staff, social worker, and others who can provide the patient with comprehensive care at the initial point of contact.”

Currently in the United States, there are no standard protocols for a psychiatric emergency, according to the National Institute of Mental Health. The online survey was conducted within the ACEP membership between July 1 through 31, 2015. The response rate was 6% and the margin of error of 2.5%.

Federal rule could cut payments for out-of-network emergency services

BY ALICIA GALLEGOS
Frontline Medical News

Emergency physician leaders expressed outrage over a new federal regulation that they say could drastically lower payments for out-of-network emergency services. The final regulation, which affirms interim regulations by the US Department of Health & Human Services (HHS), allows health plans to use a vague methodology to calculate reimbursement for out-of-network emergency services.

The American College of Emergency Physicians has worked for years to have the rule’s language revised, said Dr Jeffrey Bettinger, a member of ACEP’s reimbursement committee and founder of a health care business consulting firm in Pinecrest, Florida. “They released final regulations which not only kept worrisome language...but actually made it worse.”

The regulation, published November 18 in the Federal Register, outlines patient protections under the Affordable Care Act, including how health plans must calculate coverage for out-of-network emergency services.¹ The regulation states that a patient’s group health plan must reimburse out-of-network emergency services by paying the greatest of three possible (GOT) amounts:

• The median amount negotiated with in-network providers for the emergency service furnished.
• The amount for the emergency service calculated using the same method the plan generally uses to determine payments for out-of-network services (such as the usual, customary, and reasonable amount).
• The amount that would be paid under Medicare for the emergency service.

Under these options, the second choice is nearly always the greatest of the three amounts, and the last option–Medicare’s rate–is likely to be lowest, Dr Bettinger said.

ACEP has long been concerned about the second option because it lacks specificity and essentially leaves it up to health insurance plans to establish a Medicare-related method to reimburse emergency physicians for out-of-network services. The college lobbied for government officials to require more transparency from insurers who chose to pay under option two– for instance, by tying their methods to a usual, customary, and reasonable database or another model that was academically validated, Dr Bettinger said. The interim rule used the language, “such as the usual, customary, and reasonable charges,” rather than “amount” under option two. Under the final rule, the phrase “usual, customary, and reasonable amount,” is even more ambiguous than the proposed language, Dr Bettinger said. 

“It’s a nebulous term,” he said. “It’s totally nontransparent. There’s no database that we know of that keeps track of what that number is. Honestly, it’s interpreted by the insurance companies to dramatically lower the payments they are making for out-of-network emergency services.”

In the final regulation, HHS acknowledged concerns by health providers about the level of payment for out-of-network emergency services and the need for more transparency by insurers.

“The departments believe that this concern is addressed by our requirement that the amount be the greatest of the three amounts specified,” according to the regulation.

The final regulation does not prohibit balance billing; however, if a patient resides in a state that bans balance billing, the “greatest of three” rule does not apply. Rather, emergency physicians in such states would be reimbursed based on the unique reimbursement method for out-of-network emergency services in their state, Dr Bettinger said.

“Some states that have specific payment regulations won’t be impacted to a large degree,” he said. “Other states that have prohibitions have less clearly defined payment formulas. These states will be impacted by the final rule.”

ACEP is considering taking legal action against the government over the rule, said ACEP President Jay A. Kaplan, MD, FACEP.

 “This new ruling will significantly benefit health insurance companies at the expense of physicians, because they know hospital emergency departments have a federal mandate to care for everyone, regardless of ability to pay,” Dr Kaplan said in a statement.³ “They will continue to shift costs onto patients and medical providers, as well as shrink the number of doctors available in plans. Instead of requiring health plans to pay fairly, this ruling guarantees that insurance companies can pay whatever they want for emergency care. If history tells us anything, it’s that insurance companies prefer to pay as close to nothing as possible, while building their war chest for profits and litigation.”³

HHS officials did not respond to requests for comment.

Senate calls for childproof packaging for ‘e-cig juice’

BY GREGORY TWACHTMAN
Frontline Medical News

The Senate passed a bill that would require childproof packaging for liquid nicotine products.

The Child Nicotine Poisoning Prevention Act of 2015 (S. 142), also would codify Food and Drug Administration authority to regulate the packaging of liquid nicotine that is used to refill various electronic nicotine delivery systems.

S. 142 passed by unanimous consent in the Senate on December 10. The House of Representatives has not taken action on the bill.

“Just a small amount of this stuff can injure or even kill a small child,” Sen. Bill Nelson (D-Fla.), the bill’s sponsor, said in a statement. “Making these bottles childproof is just common sense.”

In 2014, poison control centers received more than 3,000 calls related to e-cigarette nicotine exposure, including one toddler death, according to a statement¹ from the American Academy of Pediatrics.

“With e-cigarettes becoming more and more common in households across the country, we cannot afford to wait another day to protect children from poisonous liquid nicotine,” AAP President Dr Sandra Hassink said in the statement.¹

Federal rule could cut payments for out-of-network emergency services

BY ALICIA GALLEGOS
Frontline Medical News

Emergency physician leaders expressed outrage over a new federal regulation that they say could drastically lower payments for out-of-network emergency services. The final regulation, which affirms interim regulations by the US Department of Health & Human Services (HHS), allows health plans to use a vague methodology to calculate reimbursement for out-of-network emergency services.

The American College of Emergency Physicians has worked for years to have the rule’s language revised, said Dr Jeffrey Bettinger, a member of ACEP’s reimbursement committee and founder of a health care business consulting firm in Pinecrest, Florida. “They released final regulations which not only kept worrisome language...but actually made it worse.”

The regulation, published November 18 in the Federal Register, outlines patient protections under the Affordable Care Act, including how health plans must calculate coverage for out-of-network emergency services.¹ The regulation states that a patient’s group health plan must reimburse out-of-network emergency services by paying the greatest of three possible (GOT) amounts:

• The median amount negotiated with in-network providers for the emergency service furnished.
• The amount for the emergency service calculated using the same method the plan generally uses to determine payments for out-of-network services (such as the usual, customary, and reasonable amount).
• The amount that would be paid under Medicare for the emergency service.

Under these options, the second choice is nearly always the greatest of the three amounts, and the last option–Medicare’s rate–is likely to be lowest, Dr Bettinger said.

ACEP has long been concerned about the second option because it lacks specificity and essentially leaves it up to health insurance plans to establish a Medicare-related method to reimburse emergency physicians for out-of-network services. The college lobbied for government officials to require more transparency from insurers who chose to pay under option two– for instance, by tying their methods to a usual, customary, and reasonable database or another model that was academically validated, Dr Bettinger said. The interim rule used the language, “such as the usual, customary, and reasonable charges,” rather than “amount” under option two. Under the final rule, the phrase “usual, customary, and reasonable amount,” is even more ambiguous than the proposed language, Dr Bettinger said. 

“It’s a nebulous term,” he said. “It’s totally nontransparent. There’s no database that we know of that keeps track of what that number is. Honestly, it’s interpreted by the insurance companies to dramatically lower the payments they are making for out-of-network emergency services.”

In the final regulation, HHS acknowledged concerns by health providers about the level of payment for out-of-network emergency services and the need for more transparency by insurers.

“The departments believe that this concern is addressed by our requirement that the amount be the greatest of the three amounts specified,” according to the regulation.

The final regulation does not prohibit balance billing; however, if a patient resides in a state that bans balance billing, the “greatest of three” rule does not apply. Rather, emergency physicians in such states would be reimbursed based on the unique reimbursement method for out-of-network emergency services in their state, Dr Bettinger said.

“Some states that have specific payment regulations won’t be impacted to a large degree,” he said. “Other states that have prohibitions have less clearly defined payment formulas. These states will be impacted by the final rule.”

ACEP is considering taking legal action against the government over the rule, said ACEP President Jay A. Kaplan, MD, FACEP.

 “This new ruling will significantly benefit health insurance companies at the expense of physicians, because they know hospital emergency departments have a federal mandate to care for everyone, regardless of ability to pay,” Dr Kaplan said in a statement.³ “They will continue to shift costs onto patients and medical providers, as well as shrink the number of doctors available in plans. Instead of requiring health plans to pay fairly, this ruling guarantees that insurance companies can pay whatever they want for emergency care. If history tells us anything, it’s that insurance companies prefer to pay as close to nothing as possible, while building their war chest for profits and litigation.”³

HHS officials did not respond to requests for comment.

Senate calls for childproof packaging for ‘e-cig juice’

BY GREGORY TWACHTMAN
Frontline Medical News

The Senate passed a bill that would require childproof packaging for liquid nicotine products.

The Child Nicotine Poisoning Prevention Act of 2015 (S. 142), also would codify Food and Drug Administration authority to regulate the packaging of liquid nicotine that is used to refill various electronic nicotine delivery systems.

S. 142 passed by unanimous consent in the Senate on December 10. The House of Representatives has not taken action on the bill.

“Just a small amount of this stuff can injure or even kill a small child,” Sen. Bill Nelson (D-Fla.), the bill’s sponsor, said in a statement. “Making these bottles childproof is just common sense.”

In 2014, poison control centers received more than 3,000 calls related to e-cigarette nicotine exposure, including one toddler death, according to a statement¹ from the American Academy of Pediatrics.

“With e-cigarettes becoming more and more common in households across the country, we cannot afford to wait another day to protect children from poisonous liquid nicotine,” AAP President Dr Sandra Hassink said in the statement.¹

Federal rule could cut payments for out-of-network emergency services

BY ALICIA GALLEGOS
Frontline Medical News

Emergency physician leaders expressed outrage over a new federal regulation that they say could drastically lower payments for out-of-network emergency services. The final regulation, which affirms interim regulations by the US Department of Health & Human Services (HHS), allows health plans to use a vague methodology to calculate reimbursement for out-of-network emergency services.

The American College of Emergency Physicians has worked for years to have the rule’s language revised, said Dr Jeffrey Bettinger, a member of ACEP’s reimbursement committee and founder of a health care business consulting firm in Pinecrest, Florida. “They released final regulations which not only kept worrisome language...but actually made it worse.”

The regulation, published November 18 in the Federal Register, outlines patient protections under the Affordable Care Act, including how health plans must calculate coverage for out-of-network emergency services.¹ The regulation states that a patient’s group health plan must reimburse out-of-network emergency services by paying the greatest of three possible (GOT) amounts:

• The median amount negotiated with in-network providers for the emergency service furnished.
• The amount for the emergency service calculated using the same method the plan generally uses to determine payments for out-of-network services (such as the usual, customary, and reasonable amount).
• The amount that would be paid under Medicare for the emergency service.

Under these options, the second choice is nearly always the greatest of the three amounts, and the last option–Medicare’s rate–is likely to be lowest, Dr Bettinger said.

ACEP has long been concerned about the second option because it lacks specificity and essentially leaves it up to health insurance plans to establish a Medicare-related method to reimburse emergency physicians for out-of-network services. The college lobbied for government officials to require more transparency from insurers who chose to pay under option two– for instance, by tying their methods to a usual, customary, and reasonable database or another model that was academically validated, Dr Bettinger said. The interim rule used the language, “such as the usual, customary, and reasonable charges,” rather than “amount” under option two. Under the final rule, the phrase “usual, customary, and reasonable amount,” is even more ambiguous than the proposed language, Dr Bettinger said. 

“It’s a nebulous term,” he said. “It’s totally nontransparent. There’s no database that we know of that keeps track of what that number is. Honestly, it’s interpreted by the insurance companies to dramatically lower the payments they are making for out-of-network emergency services.”

In the final regulation, HHS acknowledged concerns by health providers about the level of payment for out-of-network emergency services and the need for more transparency by insurers.

“The departments believe that this concern is addressed by our requirement that the amount be the greatest of the three amounts specified,” according to the regulation.

The final regulation does not prohibit balance billing; however, if a patient resides in a state that bans balance billing, the “greatest of three” rule does not apply. Rather, emergency physicians in such states would be reimbursed based on the unique reimbursement method for out-of-network emergency services in their state, Dr Bettinger said.

“Some states that have specific payment regulations won’t be impacted to a large degree,” he said. “Other states that have prohibitions have less clearly defined payment formulas. These states will be impacted by the final rule.”

ACEP is considering taking legal action against the government over the rule, said ACEP President Jay A. Kaplan, MD, FACEP.

 “This new ruling will significantly benefit health insurance companies at the expense of physicians, because they know hospital emergency departments have a federal mandate to care for everyone, regardless of ability to pay,” Dr Kaplan said in a statement.³ “They will continue to shift costs onto patients and medical providers, as well as shrink the number of doctors available in plans. Instead of requiring health plans to pay fairly, this ruling guarantees that insurance companies can pay whatever they want for emergency care. If history tells us anything, it’s that insurance companies prefer to pay as close to nothing as possible, while building their war chest for profits and litigation.”³

HHS officials did not respond to requests for comment.

Senate calls for childproof packaging for ‘e-cig juice’

BY GREGORY TWACHTMAN
Frontline Medical News

The Senate passed a bill that would require childproof packaging for liquid nicotine products.

The Child Nicotine Poisoning Prevention Act of 2015 (S. 142), also would codify Food and Drug Administration authority to regulate the packaging of liquid nicotine that is used to refill various electronic nicotine delivery systems.

S. 142 passed by unanimous consent in the Senate on December 10. The House of Representatives has not taken action on the bill.

“Just a small amount of this stuff can injure or even kill a small child,” Sen. Bill Nelson (D-Fla.), the bill’s sponsor, said in a statement. “Making these bottles childproof is just common sense.”

In 2014, poison control centers received more than 3,000 calls related to e-cigarette nicotine exposure, including one toddler death, according to a statement¹ from the American Academy of Pediatrics.

“With e-cigarettes becoming more and more common in households across the country, we cannot afford to wait another day to protect children from poisonous liquid nicotine,” AAP President Dr Sandra Hassink said in the statement.¹

New CPR Guide Sets Compression Limits, Scratches Vasopressin

By Shannon Aymes
From Circulation

New guidelines on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) set upper limits on chest compression rate and depth, add naloxone to the care of suspected opioid abusers, and remove vasopressin from the advanced cardiac life support (ACLS) algorithm.

The American Heart Association (AHA) published its revised guidelines October 15 in Circulation.¹ The AHA released its previous guidelines in 2010.²

“When everyone knows their role, knows CPR, and works together, we can dramatically improve cardiac arrest victims’ chances of survival,” Dr Mark Creager, AHA president and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, said in a statement.

The 2015 guidelines’ new recommendations include the following:

Resuscitation pathways. The guidelines note that the resuscitation pathways are very different for patients who experience cardiac arrest present in either a hospital setting (IHCA) or out-of-hospital setting (OHCA). In an OHCA, the patient depends on lay rescuers to not only recognize the situation but also call for help, initiate CPR, and, if available, administer defibrillation until emergency medical personnel arrive. However, IHCA involves prevention of cardiac arrest and smooth delivery of care in a multidisciplinary setting.

Compression rate and depth. The new guidelines set upper limits on chest compression depth and heart rate, recommending a compression rate of 100-120 compressions per minute with a depth of at least 2 inches, not to exceed 2.4 inches in adults.

Social media dispatching. Despite limited evidence, the guideline authors said that it may be reasonable for communities to use social media technologies to alert lay rescuers with mobile phones about nearby OHCA cases.

Naloxone and opioid addiction. Also new to the guidelines is the recommended use of naloxone for patients with suspected or known opioid addiction by appropriately trained lay rescuers or basic life support (BLS) providers.

CPR training. The guidelines highlight several changes to simplify health care provider training in CPR. For example, trained rescuers can simultaneously perform some tasks to reduce the time to initiate chest compressions. Likewise, in a team of trained rescuers, multiple steps—such as activating the emergency response system, chest compression, ventilation, and defibrillator retrieval—can be accomplished simultaneously.

High-quality CPR. The guidelines focus on emphasizing high-quality CPR with adequate compression rate and depth, complete chest recoil, few interruptions to compressions, and appropriate ventilation.

The guidelines offer several changes to advanced cardiac life support (ACLS). The algorithm was simplified by removing vasopressin, because the authors note that “the combined use of vasopressin and epinephrine offers no advantage to using standard-dose epinephrine in cardiac arrest.”

Likewise, the guidelines note conflicting studies to support the use of lidocaine after return of spontaneous circulation (ROSC). “However, the initiation or continuation of lidocaine may be considered immediately after ROSC from VF/pulseless ventricular tachycardia cardiac arrest,” the guideline authors wrote.

Finally, the guidelines highlight updates in post–cardiac arrest care, including a wider range of target temperatures, between 32°C and 36°C, to be maintained for at least 24 hours in comatose adults with ROSC after cardiac arrest. In comparison, the 2010 guidelines called for a target temperature range of 32°C to 34°C for 12 to 24 hours.

The guidelines also detail new updates for acute coronary syndrome, pediatric BLS, pediatric ACLS, and neonatal resuscitation. 

Complex Picture Emerges of Prescription Opioid Abuse

By Mary Ann Moon
From JAMA

These findings—from an analysis of two large nationally representative data sets—paint a picture that is complex and more nuanced than that suggested by some recent reports. For example, a study of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System found that the abuse and diversion of prescription opioids plateaued or decreased in recent years.³ “The nationally representative results in our study may be especially important in providing an accurate picture of the current status of the epidemic,” said Dr Beth Han of the Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, Maryland, and her associates.

The nonmedical use of prescription opioids is an acknowledged epidemic, but that epidemic’s changing pattern over time needed to be updated. The investigators assessed the changes in use during the most recent decade for which data are available (2003-2013) using annual surveys conducted by SAMHSA and cause of death files from the National Vital Statistics System.

Based on responses from 472,200 people aged 18 to 64 years, the 1-year prevalence of nonmedical use of prescription opioids decreased from 5.4% to 4.9% during the study period. However, the 1-year prevalence of use disorders rose from 0.6% to 0.9%, the 1-year prevalence of high-frequency use (200 days or more per year) increased from 0.3% to 0.4%, and the rate of opioid-related deaths increased from 4.5 per 100,000 to 7.8 per 100,000. In addition, the mean number of days of opioid abuse increased from 2.1 to 2.6 per year in the general population and from 40.0 to 54.2 days per year among acknowledged opioid users, the investigators said.¹

Compared with white users of prescription opioids, both black and Hispanic users had a lower prevalence of use disorders. The prevalence of use disorders was higher among less-educated than more-educated adults, among those with no health insurance or Medicaid as opposed to private health insurance, and among smokers than nonsmokers, Dr Han and her associates added.

Previous research has shown that most adults who abuse prescription opioids neither receive treatment nor perceive that they need treatment. Clinicians can help by using prescription-drug monitoring programs to identify inappropriate receipt of prescription opioids, then offering treatments, which are highly effective, for patients who need them, the investigators noted.

US Injury Costs Topped $671 Billion in 2013

By Richard Franki
From MMWR

Over 30 million injuries were treated in US EDs in 2013, costing an estimated $671 billion, the CDC reported.

The largest share of that cost—almost $290 billion, or about 43%—came from the 3 million persons with nonfatal injuries who were hospitalized. Costs for the 27 million people who were treated and released from EDs were $167 billion, which was just under 25% of the total. The lifetime cost estimate for the almost 193,000 injury-associated deaths in 2013 was over $214 billion (32%), said Curtis Florence, PhD, of the CDC’s National Center for Injury Prevention and Control, Atlanta, Georgia, and associates.

For each ED-treated injury-related death, the mean cost in terms of lost lifetime earnings and medical care provided was just over $1.1 million: Homicides cost over $1.6 million, suicides were $1.2 million each, and each unintentional injury death cost just under $1 million, they said.¹

Drug poisonings, including prescription drug overdoses, accounted for the largest share of fatal injury costs (27%), followed by transportation-related deaths (23%) and firearm-related deaths (22%), Dr Florence and associates noted.

“Injuries cost Americans far too much money, suffering, and preventable death,” CDC Director Tom Frieden said in a written statement. “The doubling of deaths by drug poisoning, including prescription drug overdose and heroin, is particularly alarming.”

The investigators used data from the National Vital Statistics System and the Web-Based Injury Statistics Query and Reporting System (WISQARS) for injury-related deaths and the National Electronic Injury Surveillance System–All Injury Program and WISQARS for nonfatal injuries.

Peramivir Effective Against Most Flu Viruses Circulating Globally

By Doug Brunk
AT ICAAC 2015

SAN DIEGO – The neuraminidase inhibitor peramivir inhibited about 99% of seasonal influenza A and B viruses circulating globally during the 2013 to 2014 and 2014 to 2015 influenza seasons, a large analysis demonstrated.

“The frequency of H1N1pdm09 viruses carrying neuraminidase (NA) H275Y remained low during both seasons; this mutation confers resistance to oseltamivir and peramivir,” said Margaret Okomo-Adhiambo, PhD, at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC/ICC 2015). In addition, “a small proportion of viruses contained other neuraminidase changes that affect binding of peramivir to viral enzymes and may decrease virus susceptibility. These changes need to be closely monitored.”

Approved by the FDA in December of 2014, peramivir (Rapivab) is the only antiviral agent for influenza treatment to come to market in nearly 20 years. Approved for intravenous administration as a single dose, it is indicated for adults with acute uncomplicated influenza who may have trouble taking orally administered or inhaled neuraminidase (NA) inhibitors. Other NA inhibitors approved by the FDA for influenza infection include oseltamivir, which is orally administered, and zanamivir, which is inhaled.

For the current analysis, Dr Okomo-Adhiambo of the influenza division at the US Centers for Disease Control and Prevention (CDC), Atlanta, and her associates tested influenza virus susceptibility to peramivir during the 2013-2014 and 2014-2015 influenza seasons as part of the World Health Organization Global Influenza Surveillance and Response System. A total of 8,426 viruses were tested, 75% of which were circulating in the United States.¹

Dr Okomo-Adhiambo reported that during the 2013-2014 and 2014-2015 influenza seasons, about 99% of influenza type A and B viruses were inhibited by peramivir, except for a few viruses belonging to subtype A(H1N1)pdm09 (1.5%), subtype A(H3N2) (0.2%), and type B (0.4%). In addition, NA activity of type A viruses was five to six times more sensitive to inhibition by peramivir, compared with type B NA.

Parasitic Infection Emerging in the Southwestern United States

By Doug Brunk
At IDWEEK 2015

SAN DIEGO – Onchocerca lupi, a zoonotic parasite previously described as causing eye disease in cats and dogs, as well as in humans from Europe, Asia, and the Middle East, is emerging in the Southwestern United States.

“The life cycle of this organism is not yet clearly defined, but likely includes a canine and/or feline animal reservoir, as well as an insect vector,” Dr Christiana Smith said in an interview at an annual scientific meeting on infectious diseases.¹ “No specific risk factors for developing this disease have been identified, other than residing in or traveling through the Southwestern US.”

To date, six cases of humans infected by Onchocerca lupi have come to the attention of health officials, including those at the CDC, due to symptoms from a nodule containing the parasite, according to Dr Smith, a pediatrician with the University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora. The affected patients range in age from 22 months to 50 years of age; three of the six reside in Arizona, two in New Mexico, and one in Texas.

In three of the six cases, the nodule was located in the cervical spinal canal. In the remaining three cases, nodules were located on the scalp, the forearm, and the superior rectus muscle of the orbit. Two of the patients reported insect bites at the nodule site years prior to presentation, while another patient owned a dog with eye lesions.

“No previous Onchocerca parasites are known to have tropism for the central nervous system,” Dr Smith said. “In addition, five of the six cases presented in children. It is not clear whether children are disproportionately affected by this disease, or whether they are diagnosed more frequently.”

Treatment included surgical excision and antiparasitic treatment for most cases. To date, all patients have remained asymptomatic following treatment. Dr Smith said that more information about Onchocerca lupi will become available as additional cases are described. “Continued epidemiologic investigation will help define the life cycle of this organism, describe the spectrum of human disease, develop approaches to diagnosis and management, and design prevention strategies,” she said.

IDWeek marks the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The researchers reported having no financial disclosures.

Europeans Adopt 1-Hour ED Chest Pain Triage

By Bruce Jancin
At the ESC Congress 2015

LONDON – The positive findings of the Biomarkers in Acute Cardiovascular Care (BACC) study1 reinforce a key change contained in the brand-new European Society of Cardiology guidelines for management of patients with acute coronary syndrome without ST-segment elevation: namely, that it’s appropriate to assess such patients using two measurements of a validated high-sensitivity cardiac troponin assay taken just 1 hour apart, according to Dr Kurt Huber.

The BACC results are the evidence-based icing on the cake in support of the new recommendation in the guidelines, released at the annual congress of the European Society of Cardiology. The BACC study, which included 1,045 patients who presented to a university ED with acute chest pain suggestive of an acute coronary syndrome without ST-segment elevation, was the latest of several studies to show that most such patients can either be safely sent home from the ED or ruled-in for acute MI in just 1 hour when evaluated using a high-sensitivity troponin assay backed by a validated patient-management algorithm. The result means reduced pressure on overcrowded EDs and less patient anxiety because of delayed diagnosis, Dr Huber, director of cardiology and emergency medicine at Wilhelminen Hospital in Vienna, observed during an interview at the meeting.

The BACC study, presented by Dr Dirk Westermann of the University Heart Center Hamburg (Germany), utilized a high-sensitivity cardiac troponin I assay. The 1-hour algorithm had a 99.7% negative predictive value for acute MI. A total of 53% of patients were ruled out or in for MI at the 1-hour mark; the rest required further evaluation.²

To view the video, search “Huber” at http://www.emed-journal.com/

New CPR Guide Sets Compression Limits, Scratches Vasopressin

By Shannon Aymes
From Circulation

New guidelines on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) set upper limits on chest compression rate and depth, add naloxone to the care of suspected opioid abusers, and remove vasopressin from the advanced cardiac life support (ACLS) algorithm.

The American Heart Association (AHA) published its revised guidelines October 15 in Circulation.¹ The AHA released its previous guidelines in 2010.²

“When everyone knows their role, knows CPR, and works together, we can dramatically improve cardiac arrest victims’ chances of survival,” Dr Mark Creager, AHA president and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, said in a statement.

The 2015 guidelines’ new recommendations include the following:

Resuscitation pathways. The guidelines note that the resuscitation pathways are very different for patients who experience cardiac arrest present in either a hospital setting (IHCA) or out-of-hospital setting (OHCA). In an OHCA, the patient depends on lay rescuers to not only recognize the situation but also call for help, initiate CPR, and, if available, administer defibrillation until emergency medical personnel arrive. However, IHCA involves prevention of cardiac arrest and smooth delivery of care in a multidisciplinary setting.

Compression rate and depth. The new guidelines set upper limits on chest compression depth and heart rate, recommending a compression rate of 100-120 compressions per minute with a depth of at least 2 inches, not to exceed 2.4 inches in adults.

Social media dispatching. Despite limited evidence, the guideline authors said that it may be reasonable for communities to use social media technologies to alert lay rescuers with mobile phones about nearby OHCA cases.

Naloxone and opioid addiction. Also new to the guidelines is the recommended use of naloxone for patients with suspected or known opioid addiction by appropriately trained lay rescuers or basic life support (BLS) providers.

CPR training. The guidelines highlight several changes to simplify health care provider training in CPR. For example, trained rescuers can simultaneously perform some tasks to reduce the time to initiate chest compressions. Likewise, in a team of trained rescuers, multiple steps—such as activating the emergency response system, chest compression, ventilation, and defibrillator retrieval—can be accomplished simultaneously.

High-quality CPR. The guidelines focus on emphasizing high-quality CPR with adequate compression rate and depth, complete chest recoil, few interruptions to compressions, and appropriate ventilation.

The guidelines offer several changes to advanced cardiac life support (ACLS). The algorithm was simplified by removing vasopressin, because the authors note that “the combined use of vasopressin and epinephrine offers no advantage to using standard-dose epinephrine in cardiac arrest.”

Likewise, the guidelines note conflicting studies to support the use of lidocaine after return of spontaneous circulation (ROSC). “However, the initiation or continuation of lidocaine may be considered immediately after ROSC from VF/pulseless ventricular tachycardia cardiac arrest,” the guideline authors wrote.

Finally, the guidelines highlight updates in post–cardiac arrest care, including a wider range of target temperatures, between 32°C and 36°C, to be maintained for at least 24 hours in comatose adults with ROSC after cardiac arrest. In comparison, the 2010 guidelines called for a target temperature range of 32°C to 34°C for 12 to 24 hours.

The guidelines also detail new updates for acute coronary syndrome, pediatric BLS, pediatric ACLS, and neonatal resuscitation. 

Complex Picture Emerges of Prescription Opioid Abuse

By Mary Ann Moon
From JAMA

These findings—from an analysis of two large nationally representative data sets—paint a picture that is complex and more nuanced than that suggested by some recent reports. For example, a study of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System found that the abuse and diversion of prescription opioids plateaued or decreased in recent years.³ “The nationally representative results in our study may be especially important in providing an accurate picture of the current status of the epidemic,” said Dr Beth Han of the Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, Maryland, and her associates.

The nonmedical use of prescription opioids is an acknowledged epidemic, but that epidemic’s changing pattern over time needed to be updated. The investigators assessed the changes in use during the most recent decade for which data are available (2003-2013) using annual surveys conducted by SAMHSA and cause of death files from the National Vital Statistics System.

Based on responses from 472,200 people aged 18 to 64 years, the 1-year prevalence of nonmedical use of prescription opioids decreased from 5.4% to 4.9% during the study period. However, the 1-year prevalence of use disorders rose from 0.6% to 0.9%, the 1-year prevalence of high-frequency use (200 days or more per year) increased from 0.3% to 0.4%, and the rate of opioid-related deaths increased from 4.5 per 100,000 to 7.8 per 100,000. In addition, the mean number of days of opioid abuse increased from 2.1 to 2.6 per year in the general population and from 40.0 to 54.2 days per year among acknowledged opioid users, the investigators said.¹

Compared with white users of prescription opioids, both black and Hispanic users had a lower prevalence of use disorders. The prevalence of use disorders was higher among less-educated than more-educated adults, among those with no health insurance or Medicaid as opposed to private health insurance, and among smokers than nonsmokers, Dr Han and her associates added.

Previous research has shown that most adults who abuse prescription opioids neither receive treatment nor perceive that they need treatment. Clinicians can help by using prescription-drug monitoring programs to identify inappropriate receipt of prescription opioids, then offering treatments, which are highly effective, for patients who need them, the investigators noted.

US Injury Costs Topped $671 Billion in 2013

By Richard Franki
From MMWR

Over 30 million injuries were treated in US EDs in 2013, costing an estimated $671 billion, the CDC reported.

The largest share of that cost—almost $290 billion, or about 43%—came from the 3 million persons with nonfatal injuries who were hospitalized. Costs for the 27 million people who were treated and released from EDs were $167 billion, which was just under 25% of the total. The lifetime cost estimate for the almost 193,000 injury-associated deaths in 2013 was over $214 billion (32%), said Curtis Florence, PhD, of the CDC’s National Center for Injury Prevention and Control, Atlanta, Georgia, and associates.

For each ED-treated injury-related death, the mean cost in terms of lost lifetime earnings and medical care provided was just over $1.1 million: Homicides cost over $1.6 million, suicides were $1.2 million each, and each unintentional injury death cost just under $1 million, they said.¹

Drug poisonings, including prescription drug overdoses, accounted for the largest share of fatal injury costs (27%), followed by transportation-related deaths (23%) and firearm-related deaths (22%), Dr Florence and associates noted.

“Injuries cost Americans far too much money, suffering, and preventable death,” CDC Director Tom Frieden said in a written statement. “The doubling of deaths by drug poisoning, including prescription drug overdose and heroin, is particularly alarming.”

The investigators used data from the National Vital Statistics System and the Web-Based Injury Statistics Query and Reporting System (WISQARS) for injury-related deaths and the National Electronic Injury Surveillance System–All Injury Program and WISQARS for nonfatal injuries.

Peramivir Effective Against Most Flu Viruses Circulating Globally

By Doug Brunk
AT ICAAC 2015

SAN DIEGO – The neuraminidase inhibitor peramivir inhibited about 99% of seasonal influenza A and B viruses circulating globally during the 2013 to 2014 and 2014 to 2015 influenza seasons, a large analysis demonstrated.

“The frequency of H1N1pdm09 viruses carrying neuraminidase (NA) H275Y remained low during both seasons; this mutation confers resistance to oseltamivir and peramivir,” said Margaret Okomo-Adhiambo, PhD, at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC/ICC 2015). In addition, “a small proportion of viruses contained other neuraminidase changes that affect binding of peramivir to viral enzymes and may decrease virus susceptibility. These changes need to be closely monitored.”

Approved by the FDA in December of 2014, peramivir (Rapivab) is the only antiviral agent for influenza treatment to come to market in nearly 20 years. Approved for intravenous administration as a single dose, it is indicated for adults with acute uncomplicated influenza who may have trouble taking orally administered or inhaled neuraminidase (NA) inhibitors. Other NA inhibitors approved by the FDA for influenza infection include oseltamivir, which is orally administered, and zanamivir, which is inhaled.

For the current analysis, Dr Okomo-Adhiambo of the influenza division at the US Centers for Disease Control and Prevention (CDC), Atlanta, and her associates tested influenza virus susceptibility to peramivir during the 2013-2014 and 2014-2015 influenza seasons as part of the World Health Organization Global Influenza Surveillance and Response System. A total of 8,426 viruses were tested, 75% of which were circulating in the United States.¹

Dr Okomo-Adhiambo reported that during the 2013-2014 and 2014-2015 influenza seasons, about 99% of influenza type A and B viruses were inhibited by peramivir, except for a few viruses belonging to subtype A(H1N1)pdm09 (1.5%), subtype A(H3N2) (0.2%), and type B (0.4%). In addition, NA activity of type A viruses was five to six times more sensitive to inhibition by peramivir, compared with type B NA.

Parasitic Infection Emerging in the Southwestern United States

By Doug Brunk
At IDWEEK 2015

SAN DIEGO – Onchocerca lupi, a zoonotic parasite previously described as causing eye disease in cats and dogs, as well as in humans from Europe, Asia, and the Middle East, is emerging in the Southwestern United States.

“The life cycle of this organism is not yet clearly defined, but likely includes a canine and/or feline animal reservoir, as well as an insect vector,” Dr Christiana Smith said in an interview at an annual scientific meeting on infectious diseases.¹ “No specific risk factors for developing this disease have been identified, other than residing in or traveling through the Southwestern US.”

To date, six cases of humans infected by Onchocerca lupi have come to the attention of health officials, including those at the CDC, due to symptoms from a nodule containing the parasite, according to Dr Smith, a pediatrician with the University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora. The affected patients range in age from 22 months to 50 years of age; three of the six reside in Arizona, two in New Mexico, and one in Texas.

In three of the six cases, the nodule was located in the cervical spinal canal. In the remaining three cases, nodules were located on the scalp, the forearm, and the superior rectus muscle of the orbit. Two of the patients reported insect bites at the nodule site years prior to presentation, while another patient owned a dog with eye lesions.

“No previous Onchocerca parasites are known to have tropism for the central nervous system,” Dr Smith said. “In addition, five of the six cases presented in children. It is not clear whether children are disproportionately affected by this disease, or whether they are diagnosed more frequently.”

Treatment included surgical excision and antiparasitic treatment for most cases. To date, all patients have remained asymptomatic following treatment. Dr Smith said that more information about Onchocerca lupi will become available as additional cases are described. “Continued epidemiologic investigation will help define the life cycle of this organism, describe the spectrum of human disease, develop approaches to diagnosis and management, and design prevention strategies,” she said.

IDWeek marks the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The researchers reported having no financial disclosures.

Europeans Adopt 1-Hour ED Chest Pain Triage

By Bruce Jancin
At the ESC Congress 2015

LONDON – The positive findings of the Biomarkers in Acute Cardiovascular Care (BACC) study1 reinforce a key change contained in the brand-new European Society of Cardiology guidelines for management of patients with acute coronary syndrome without ST-segment elevation: namely, that it’s appropriate to assess such patients using two measurements of a validated high-sensitivity cardiac troponin assay taken just 1 hour apart, according to Dr Kurt Huber.

The BACC results are the evidence-based icing on the cake in support of the new recommendation in the guidelines, released at the annual congress of the European Society of Cardiology. The BACC study, which included 1,045 patients who presented to a university ED with acute chest pain suggestive of an acute coronary syndrome without ST-segment elevation, was the latest of several studies to show that most such patients can either be safely sent home from the ED or ruled-in for acute MI in just 1 hour when evaluated using a high-sensitivity troponin assay backed by a validated patient-management algorithm. The result means reduced pressure on overcrowded EDs and less patient anxiety because of delayed diagnosis, Dr Huber, director of cardiology and emergency medicine at Wilhelminen Hospital in Vienna, observed during an interview at the meeting.

The BACC study, presented by Dr Dirk Westermann of the University Heart Center Hamburg (Germany), utilized a high-sensitivity cardiac troponin I assay. The 1-hour algorithm had a 99.7% negative predictive value for acute MI. A total of 53% of patients were ruled out or in for MI at the 1-hour mark; the rest required further evaluation.²

To view the video, search “Huber” at http://www.emed-journal.com/

New CPR Guide Sets Compression Limits, Scratches Vasopressin

By Shannon Aymes
From Circulation

New guidelines on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) set upper limits on chest compression rate and depth, add naloxone to the care of suspected opioid abusers, and remove vasopressin from the advanced cardiac life support (ACLS) algorithm.

The American Heart Association (AHA) published its revised guidelines October 15 in Circulation.¹ The AHA released its previous guidelines in 2010.²

“When everyone knows their role, knows CPR, and works together, we can dramatically improve cardiac arrest victims’ chances of survival,” Dr Mark Creager, AHA president and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, said in a statement.

The 2015 guidelines’ new recommendations include the following:

Resuscitation pathways. The guidelines note that the resuscitation pathways are very different for patients who experience cardiac arrest present in either a hospital setting (IHCA) or out-of-hospital setting (OHCA). In an OHCA, the patient depends on lay rescuers to not only recognize the situation but also call for help, initiate CPR, and, if available, administer defibrillation until emergency medical personnel arrive. However, IHCA involves prevention of cardiac arrest and smooth delivery of care in a multidisciplinary setting.

Compression rate and depth. The new guidelines set upper limits on chest compression depth and heart rate, recommending a compression rate of 100-120 compressions per minute with a depth of at least 2 inches, not to exceed 2.4 inches in adults.

Social media dispatching. Despite limited evidence, the guideline authors said that it may be reasonable for communities to use social media technologies to alert lay rescuers with mobile phones about nearby OHCA cases.

Naloxone and opioid addiction. Also new to the guidelines is the recommended use of naloxone for patients with suspected or known opioid addiction by appropriately trained lay rescuers or basic life support (BLS) providers.

CPR training. The guidelines highlight several changes to simplify health care provider training in CPR. For example, trained rescuers can simultaneously perform some tasks to reduce the time to initiate chest compressions. Likewise, in a team of trained rescuers, multiple steps—such as activating the emergency response system, chest compression, ventilation, and defibrillator retrieval—can be accomplished simultaneously.

High-quality CPR. The guidelines focus on emphasizing high-quality CPR with adequate compression rate and depth, complete chest recoil, few interruptions to compressions, and appropriate ventilation.

The guidelines offer several changes to advanced cardiac life support (ACLS). The algorithm was simplified by removing vasopressin, because the authors note that “the combined use of vasopressin and epinephrine offers no advantage to using standard-dose epinephrine in cardiac arrest.”

Likewise, the guidelines note conflicting studies to support the use of lidocaine after return of spontaneous circulation (ROSC). “However, the initiation or continuation of lidocaine may be considered immediately after ROSC from VF/pulseless ventricular tachycardia cardiac arrest,” the guideline authors wrote.

Finally, the guidelines highlight updates in post–cardiac arrest care, including a wider range of target temperatures, between 32°C and 36°C, to be maintained for at least 24 hours in comatose adults with ROSC after cardiac arrest. In comparison, the 2010 guidelines called for a target temperature range of 32°C to 34°C for 12 to 24 hours.

The guidelines also detail new updates for acute coronary syndrome, pediatric BLS, pediatric ACLS, and neonatal resuscitation. 

Complex Picture Emerges of Prescription Opioid Abuse

By Mary Ann Moon
From JAMA

These findings—from an analysis of two large nationally representative data sets—paint a picture that is complex and more nuanced than that suggested by some recent reports. For example, a study of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System found that the abuse and diversion of prescription opioids plateaued or decreased in recent years.³ “The nationally representative results in our study may be especially important in providing an accurate picture of the current status of the epidemic,” said Dr Beth Han of the Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, Maryland, and her associates.

The nonmedical use of prescription opioids is an acknowledged epidemic, but that epidemic’s changing pattern over time needed to be updated. The investigators assessed the changes in use during the most recent decade for which data are available (2003-2013) using annual surveys conducted by SAMHSA and cause of death files from the National Vital Statistics System.

Based on responses from 472,200 people aged 18 to 64 years, the 1-year prevalence of nonmedical use of prescription opioids decreased from 5.4% to 4.9% during the study period. However, the 1-year prevalence of use disorders rose from 0.6% to 0.9%, the 1-year prevalence of high-frequency use (200 days or more per year) increased from 0.3% to 0.4%, and the rate of opioid-related deaths increased from 4.5 per 100,000 to 7.8 per 100,000. In addition, the mean number of days of opioid abuse increased from 2.1 to 2.6 per year in the general population and from 40.0 to 54.2 days per year among acknowledged opioid users, the investigators said.¹

Compared with white users of prescription opioids, both black and Hispanic users had a lower prevalence of use disorders. The prevalence of use disorders was higher among less-educated than more-educated adults, among those with no health insurance or Medicaid as opposed to private health insurance, and among smokers than nonsmokers, Dr Han and her associates added.

Previous research has shown that most adults who abuse prescription opioids neither receive treatment nor perceive that they need treatment. Clinicians can help by using prescription-drug monitoring programs to identify inappropriate receipt of prescription opioids, then offering treatments, which are highly effective, for patients who need them, the investigators noted.

US Injury Costs Topped $671 Billion in 2013

By Richard Franki
From MMWR

Over 30 million injuries were treated in US EDs in 2013, costing an estimated $671 billion, the CDC reported.

The largest share of that cost—almost $290 billion, or about 43%—came from the 3 million persons with nonfatal injuries who were hospitalized. Costs for the 27 million people who were treated and released from EDs were $167 billion, which was just under 25% of the total. The lifetime cost estimate for the almost 193,000 injury-associated deaths in 2013 was over $214 billion (32%), said Curtis Florence, PhD, of the CDC’s National Center for Injury Prevention and Control, Atlanta, Georgia, and associates.

For each ED-treated injury-related death, the mean cost in terms of lost lifetime earnings and medical care provided was just over $1.1 million: Homicides cost over $1.6 million, suicides were $1.2 million each, and each unintentional injury death cost just under $1 million, they said.¹

Drug poisonings, including prescription drug overdoses, accounted for the largest share of fatal injury costs (27%), followed by transportation-related deaths (23%) and firearm-related deaths (22%), Dr Florence and associates noted.

“Injuries cost Americans far too much money, suffering, and preventable death,” CDC Director Tom Frieden said in a written statement. “The doubling of deaths by drug poisoning, including prescription drug overdose and heroin, is particularly alarming.”

The investigators used data from the National Vital Statistics System and the Web-Based Injury Statistics Query and Reporting System (WISQARS) for injury-related deaths and the National Electronic Injury Surveillance System–All Injury Program and WISQARS for nonfatal injuries.

Peramivir Effective Against Most Flu Viruses Circulating Globally

By Doug Brunk
AT ICAAC 2015

SAN DIEGO – The neuraminidase inhibitor peramivir inhibited about 99% of seasonal influenza A and B viruses circulating globally during the 2013 to 2014 and 2014 to 2015 influenza seasons, a large analysis demonstrated.

“The frequency of H1N1pdm09 viruses carrying neuraminidase (NA) H275Y remained low during both seasons; this mutation confers resistance to oseltamivir and peramivir,” said Margaret Okomo-Adhiambo, PhD, at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC/ICC 2015). In addition, “a small proportion of viruses contained other neuraminidase changes that affect binding of peramivir to viral enzymes and may decrease virus susceptibility. These changes need to be closely monitored.”

Approved by the FDA in December of 2014, peramivir (Rapivab) is the only antiviral agent for influenza treatment to come to market in nearly 20 years. Approved for intravenous administration as a single dose, it is indicated for adults with acute uncomplicated influenza who may have trouble taking orally administered or inhaled neuraminidase (NA) inhibitors. Other NA inhibitors approved by the FDA for influenza infection include oseltamivir, which is orally administered, and zanamivir, which is inhaled.

For the current analysis, Dr Okomo-Adhiambo of the influenza division at the US Centers for Disease Control and Prevention (CDC), Atlanta, and her associates tested influenza virus susceptibility to peramivir during the 2013-2014 and 2014-2015 influenza seasons as part of the World Health Organization Global Influenza Surveillance and Response System. A total of 8,426 viruses were tested, 75% of which were circulating in the United States.¹

Dr Okomo-Adhiambo reported that during the 2013-2014 and 2014-2015 influenza seasons, about 99% of influenza type A and B viruses were inhibited by peramivir, except for a few viruses belonging to subtype A(H1N1)pdm09 (1.5%), subtype A(H3N2) (0.2%), and type B (0.4%). In addition, NA activity of type A viruses was five to six times more sensitive to inhibition by peramivir, compared with type B NA.

Parasitic Infection Emerging in the Southwestern United States

By Doug Brunk
At IDWEEK 2015

SAN DIEGO – Onchocerca lupi, a zoonotic parasite previously described as causing eye disease in cats and dogs, as well as in humans from Europe, Asia, and the Middle East, is emerging in the Southwestern United States.

“The life cycle of this organism is not yet clearly defined, but likely includes a canine and/or feline animal reservoir, as well as an insect vector,” Dr Christiana Smith said in an interview at an annual scientific meeting on infectious diseases.¹ “No specific risk factors for developing this disease have been identified, other than residing in or traveling through the Southwestern US.”

To date, six cases of humans infected by Onchocerca lupi have come to the attention of health officials, including those at the CDC, due to symptoms from a nodule containing the parasite, according to Dr Smith, a pediatrician with the University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora. The affected patients range in age from 22 months to 50 years of age; three of the six reside in Arizona, two in New Mexico, and one in Texas.

In three of the six cases, the nodule was located in the cervical spinal canal. In the remaining three cases, nodules were located on the scalp, the forearm, and the superior rectus muscle of the orbit. Two of the patients reported insect bites at the nodule site years prior to presentation, while another patient owned a dog with eye lesions.

“No previous Onchocerca parasites are known to have tropism for the central nervous system,” Dr Smith said. “In addition, five of the six cases presented in children. It is not clear whether children are disproportionately affected by this disease, or whether they are diagnosed more frequently.”

Treatment included surgical excision and antiparasitic treatment for most cases. To date, all patients have remained asymptomatic following treatment. Dr Smith said that more information about Onchocerca lupi will become available as additional cases are described. “Continued epidemiologic investigation will help define the life cycle of this organism, describe the spectrum of human disease, develop approaches to diagnosis and management, and design prevention strategies,” she said.

IDWeek marks the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The researchers reported having no financial disclosures.

Europeans Adopt 1-Hour ED Chest Pain Triage

By Bruce Jancin
At the ESC Congress 2015

LONDON – The positive findings of the Biomarkers in Acute Cardiovascular Care (BACC) study1 reinforce a key change contained in the brand-new European Society of Cardiology guidelines for management of patients with acute coronary syndrome without ST-segment elevation: namely, that it’s appropriate to assess such patients using two measurements of a validated high-sensitivity cardiac troponin assay taken just 1 hour apart, according to Dr Kurt Huber.

The BACC results are the evidence-based icing on the cake in support of the new recommendation in the guidelines, released at the annual congress of the European Society of Cardiology. The BACC study, which included 1,045 patients who presented to a university ED with acute chest pain suggestive of an acute coronary syndrome without ST-segment elevation, was the latest of several studies to show that most such patients can either be safely sent home from the ED or ruled-in for acute MI in just 1 hour when evaluated using a high-sensitivity troponin assay backed by a validated patient-management algorithm. The result means reduced pressure on overcrowded EDs and less patient anxiety because of delayed diagnosis, Dr Huber, director of cardiology and emergency medicine at Wilhelminen Hospital in Vienna, observed during an interview at the meeting.

The BACC study, presented by Dr Dirk Westermann of the University Heart Center Hamburg (Germany), utilized a high-sensitivity cardiac troponin I assay. The 1-hour algorithm had a 99.7% negative predictive value for acute MI. A total of 53% of patients were ruled out or in for MI at the 1-hour mark; the rest required further evaluation.²

To view the video, search “Huber” at http://www.emed-journal.com/

Timely Epinephrine for Pediatric In-Hospital Cardiac Arrest

BY MARY ANN MOON
FROM JAMA

Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published in JAMA.¹

For the approximately 16,000 US children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.

“It is highly unlikely that any such study will ever be done, given the ethical considerations; so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period,” said Dr Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts and the department of anesthesiology at Aarhus (Denmark) University and his associates.¹

All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.

Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (RR, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).

In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr Andersen and his associates said.

These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.

ED Care Pathway Hastens Febrile Neutropenia Therapy

BY Kari Oakes
FROM THE JOURNAL OF ONCOLOGY PRACTICE

Cancer patients who arrive in the ED with febrile neutropenia (FN) received antibiotics much more quickly when their condition was identified as a medical emergency and a care pathway was used to guide treatment. The set of simple interventions slashed average time to antibiotics from about 4 hours to less than 1.5 hours, compared with a historical cohort, and the inexpensive interventions have had durable results.

Dr Michael Keng and his coinvestigators at the Cleveland Clinic reported the results of a single-center prospective analysis that targeted FN, a common and serious chemotherapy complication with a mortality rate that can exceed 50% in medically fragile individuals.¹

“With an increasing number of outpatient chemotherapy regimens, more patients are likely to present to the emergency department with FN,” wrote Dr Keng. The FN pathway devised by Dr Keng and his associates implemented key changes designed to identify FN as an emergency and guide prompt triage, assessment, and treatment.

Study coauthor Dr Mikkael Sekeres said, “The interventions were not complicated. We standardized our definition of fever, provided patients with wallet-sized cards alerting emergency departments to the potential of this serious condition, worked with our emergency department staff to change the triage level of fever and neutropenia to be equivalent to that observed for heart attack or stroke, designed standard febrile neutropenia order sets for our electronic medical record, and relocated the antibiotics used to treat febrile neutropenia to our emergency department.”

Febrile patients with cancer in the prospective cohort (n = 223) were compared with a historical cohort of patients presenting to the ED who received usual care (n = 87), as well as to a concurrent cohort of patients who were directly admitted to the hospital (n = 114). The total number of FN episodes for the cohorts was 276, 107, and 114, respectively. Multivariable analysis was used to account for some differences in patient characteristics across cohorts.

Using the order set in the electronic health record (EHR) also made a difference: for those treated per the order set (n = 103), median time to antibiotics was 68 minutes, compared with 96 minutes when the order set was not used.

Secondary outcome measures included times to physician assessment, blood draw, and antibiotic order placement. All measures except time to physician assessment were significantly shorter for the FN pathway group than for the comparison cohorts (P<.001 for all).

Since so many changes were made at once, Dr Keng and his coauthors noted, “It is difficult to determine the impact of any one change.” Some institutions may have difficulty implementing all the interventions, but immediate triage, automated antibiotic ordering, and EHR use were the changes that had the most impact, he wrote.

“Instituting these changes took less than half a year, and the benefits have persisted for years afterward,” Dr Sekeres said in an interview.

ESC: Aldosterone Blockade Fails to Fly for Early MI in ALBATROSS

BY BRUCE JANCIN
AT THE European Society of Cardiology CONGRESS 2015

LONDON – Aldosterone blockade with oral spironolactone showed a disappointing lack of clinical benefit when initiated in the first hours after an acute MI without heart failure in the large, randomized ALBATROSS trial.

ALBATROSS did, however, flash a silver lining under one wing: A whopping 80% reduction in 6-month mortality in a prespecified subgroup analysis restricted to the 1,229 participants with ST-elevation MI, Dr Gilles Montalescot reported at the annual congress of the European Society of Cardiology.

Although this finding is intriguing, hypothesis-generating, and definitely warrants a confirmatory study, he continued, mortality was nevertheless merely a secondary endpoint in ALBATROSS.

In contrast, the primary composite outcome was negative, so the takeaway message is clear: “The results of the ALBATROSS study do not warrant the extension of aldosterone blockade to MI patients without heart failure,” said Dr Montalescot, professor of cardiology at the University of Paris.

ALBATROSS was a multicenter French trial that randomly assigned 1,603 acute MI patients to standard therapy alone or with added mineralocorticoid antagonist therapy started within the first 2 days of their coronary event. Often the aldosterone antagonist was begun in the ambulance en route to the hospital.¹

The primary endpoint was a composite of death, resuscitated cardiac arrest, ventricular fibrillation or tachycardia, heart failure, or an indication for an implantable cardioverter defibrillator. There were 194 such events, and they occurred at a similar rate in the patients who got 25 mg/day of spironolactone and those who did not.

The rationale for ALBATROSS was sound, according to the cardiologist. Aldosterone is a stress hormone released in acute MI. It has deleterious cardiac effects, including arrhythmias, heart failure, and a dose-dependent increase in mortality, so it makes good sense to block it as soon as possible in MI patients. In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, the aldosterone antagonist eplerenone, when started 3-14 days post MI in patients with early heart failure, significantly reduced mortality,² with the bulk of the benefit occurring in patients in whom the drug was started 3-7 days post MI.

Last year, Dr Montalescot and his coinvestigators published the Randomized, Placebo-Controlled Trial Evaluating The Safety and Efficacy of Early Treatment With Eplerenone in Patients With Acute Myocardial Infarction (REMINDER) study, in which 1,012 ST-elevation MI (STEMI) patients without heart failure were randomized to eplerenone or placebo within the first 24 hours. The study showed a significant reduction in levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP in the eplerenone arm,² but that’s not a clinical endpoint. ALBATROSS was the first study to look at the clinical impact of commencing mineralocorticoid antagonist therapy prior to day 3 post-MI.

Discussant Dr John McMurray, professor of cardiology at the University of Glasgow, Scotland, said that ALBATROSS was simply underpowered and thus leaves unanswered the clinically important question of whether early initiation of aldosterone blockade post MI in patients without heart failure confers clinical benefit. The investigators projected a total of 269 events in the composite endpoint but got only 194 because the study participants were so well treated and contemporary medical and interventional therapies are quite effective. 

He dismissed the sharp reduction seen in 6-month mortality with spironolactone in the STEMI patients as “just implausible—we don’t know of any treatments in medicine that reduce mortality by 80%.”

Noting that there were only 28 deaths in the study, Dr McMurray asserted that “a subgroup analysis on such a small number of events is never going to give you a reliable result.” Moreover, he added, “subgroup analysis is even more treacherous when the overall trial is underpowered.”

Dr Montalescot replied that, while he considers the signal of a mortality benefit for aldosterone blockade in STEMI patients worthy of pursuit in a large randomized trial, the prospects for mounting such a study are poor. The medications are now available as generics, so there is no commercial incentive. The French Ministry of Health, which funded ALBATROSS, isn’t prepared to back a follow-up study. The best hope is that eventually one of the pharmaceutical companies developing third-generation aldosterone antagonists, now in phase II studies, will become interested, he said.

Dr Montalescot said that, while he receives research grants and consulting fees from numerous pharmaceutical companies, these commercial relationships aren’t relevant to the government-funded ALBATROSS trial.

Inpatient Mortality Down for High-Volume Conditions

BY RICHARD FRANKI
Frontline Medical News

Over that period, mortality among adults hospitalized with pneumonia went from 65 per 1,000 admissions to 35.8 per 1,000 for a drop of 45%—the largest of the four high-volume conditions. Corresponding declines for the others were 41% for acute MI, 29% for heart failure, and 27% for stroke, the AHRQ noted.

Since “death following discharge from a hospital is not reflected in these data,” the report said, measures of inpatient mortality “can reflect both improvements in health care and shifts in where end-of-life care takes place over time.”

The estimates in the report are based on data from the Nationwide Inpatient Sample (2002-2011) and State Inpatient Databases (2012).¹

Timely Epinephrine for Pediatric In-Hospital Cardiac Arrest

BY MARY ANN MOON
FROM JAMA

Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published in JAMA.¹

For the approximately 16,000 US children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.

“It is highly unlikely that any such study will ever be done, given the ethical considerations; so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period,” said Dr Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts and the department of anesthesiology at Aarhus (Denmark) University and his associates.¹

All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.

Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (RR, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).

In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr Andersen and his associates said.

These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.

ED Care Pathway Hastens Febrile Neutropenia Therapy

BY Kari Oakes
FROM THE JOURNAL OF ONCOLOGY PRACTICE

Cancer patients who arrive in the ED with febrile neutropenia (FN) received antibiotics much more quickly when their condition was identified as a medical emergency and a care pathway was used to guide treatment. The set of simple interventions slashed average time to antibiotics from about 4 hours to less than 1.5 hours, compared with a historical cohort, and the inexpensive interventions have had durable results.

Dr Michael Keng and his coinvestigators at the Cleveland Clinic reported the results of a single-center prospective analysis that targeted FN, a common and serious chemotherapy complication with a mortality rate that can exceed 50% in medically fragile individuals.¹

“With an increasing number of outpatient chemotherapy regimens, more patients are likely to present to the emergency department with FN,” wrote Dr Keng. The FN pathway devised by Dr Keng and his associates implemented key changes designed to identify FN as an emergency and guide prompt triage, assessment, and treatment.

Study coauthor Dr Mikkael Sekeres said, “The interventions were not complicated. We standardized our definition of fever, provided patients with wallet-sized cards alerting emergency departments to the potential of this serious condition, worked with our emergency department staff to change the triage level of fever and neutropenia to be equivalent to that observed for heart attack or stroke, designed standard febrile neutropenia order sets for our electronic medical record, and relocated the antibiotics used to treat febrile neutropenia to our emergency department.”

Febrile patients with cancer in the prospective cohort (n = 223) were compared with a historical cohort of patients presenting to the ED who received usual care (n = 87), as well as to a concurrent cohort of patients who were directly admitted to the hospital (n = 114). The total number of FN episodes for the cohorts was 276, 107, and 114, respectively. Multivariable analysis was used to account for some differences in patient characteristics across cohorts.

Using the order set in the electronic health record (EHR) also made a difference: for those treated per the order set (n = 103), median time to antibiotics was 68 minutes, compared with 96 minutes when the order set was not used.

Secondary outcome measures included times to physician assessment, blood draw, and antibiotic order placement. All measures except time to physician assessment were significantly shorter for the FN pathway group than for the comparison cohorts (P<.001 for all).

Since so many changes were made at once, Dr Keng and his coauthors noted, “It is difficult to determine the impact of any one change.” Some institutions may have difficulty implementing all the interventions, but immediate triage, automated antibiotic ordering, and EHR use were the changes that had the most impact, he wrote.

“Instituting these changes took less than half a year, and the benefits have persisted for years afterward,” Dr Sekeres said in an interview.

ESC: Aldosterone Blockade Fails to Fly for Early MI in ALBATROSS

BY BRUCE JANCIN
AT THE European Society of Cardiology CONGRESS 2015

LONDON – Aldosterone blockade with oral spironolactone showed a disappointing lack of clinical benefit when initiated in the first hours after an acute MI without heart failure in the large, randomized ALBATROSS trial.

ALBATROSS did, however, flash a silver lining under one wing: A whopping 80% reduction in 6-month mortality in a prespecified subgroup analysis restricted to the 1,229 participants with ST-elevation MI, Dr Gilles Montalescot reported at the annual congress of the European Society of Cardiology.

Although this finding is intriguing, hypothesis-generating, and definitely warrants a confirmatory study, he continued, mortality was nevertheless merely a secondary endpoint in ALBATROSS.

In contrast, the primary composite outcome was negative, so the takeaway message is clear: “The results of the ALBATROSS study do not warrant the extension of aldosterone blockade to MI patients without heart failure,” said Dr Montalescot, professor of cardiology at the University of Paris.

ALBATROSS was a multicenter French trial that randomly assigned 1,603 acute MI patients to standard therapy alone or with added mineralocorticoid antagonist therapy started within the first 2 days of their coronary event. Often the aldosterone antagonist was begun in the ambulance en route to the hospital.¹

The primary endpoint was a composite of death, resuscitated cardiac arrest, ventricular fibrillation or tachycardia, heart failure, or an indication for an implantable cardioverter defibrillator. There were 194 such events, and they occurred at a similar rate in the patients who got 25 mg/day of spironolactone and those who did not.

The rationale for ALBATROSS was sound, according to the cardiologist. Aldosterone is a stress hormone released in acute MI. It has deleterious cardiac effects, including arrhythmias, heart failure, and a dose-dependent increase in mortality, so it makes good sense to block it as soon as possible in MI patients. In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, the aldosterone antagonist eplerenone, when started 3-14 days post MI in patients with early heart failure, significantly reduced mortality,² with the bulk of the benefit occurring in patients in whom the drug was started 3-7 days post MI.

Last year, Dr Montalescot and his coinvestigators published the Randomized, Placebo-Controlled Trial Evaluating The Safety and Efficacy of Early Treatment With Eplerenone in Patients With Acute Myocardial Infarction (REMINDER) study, in which 1,012 ST-elevation MI (STEMI) patients without heart failure were randomized to eplerenone or placebo within the first 24 hours. The study showed a significant reduction in levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP in the eplerenone arm,² but that’s not a clinical endpoint. ALBATROSS was the first study to look at the clinical impact of commencing mineralocorticoid antagonist therapy prior to day 3 post-MI.

Discussant Dr John McMurray, professor of cardiology at the University of Glasgow, Scotland, said that ALBATROSS was simply underpowered and thus leaves unanswered the clinically important question of whether early initiation of aldosterone blockade post MI in patients without heart failure confers clinical benefit. The investigators projected a total of 269 events in the composite endpoint but got only 194 because the study participants were so well treated and contemporary medical and interventional therapies are quite effective. 

He dismissed the sharp reduction seen in 6-month mortality with spironolactone in the STEMI patients as “just implausible—we don’t know of any treatments in medicine that reduce mortality by 80%.”

Noting that there were only 28 deaths in the study, Dr McMurray asserted that “a subgroup analysis on such a small number of events is never going to give you a reliable result.” Moreover, he added, “subgroup analysis is even more treacherous when the overall trial is underpowered.”

Dr Montalescot replied that, while he considers the signal of a mortality benefit for aldosterone blockade in STEMI patients worthy of pursuit in a large randomized trial, the prospects for mounting such a study are poor. The medications are now available as generics, so there is no commercial incentive. The French Ministry of Health, which funded ALBATROSS, isn’t prepared to back a follow-up study. The best hope is that eventually one of the pharmaceutical companies developing third-generation aldosterone antagonists, now in phase II studies, will become interested, he said.

Dr Montalescot said that, while he receives research grants and consulting fees from numerous pharmaceutical companies, these commercial relationships aren’t relevant to the government-funded ALBATROSS trial.

Inpatient Mortality Down for High-Volume Conditions

BY RICHARD FRANKI
Frontline Medical News

Over that period, mortality among adults hospitalized with pneumonia went from 65 per 1,000 admissions to 35.8 per 1,000 for a drop of 45%—the largest of the four high-volume conditions. Corresponding declines for the others were 41% for acute MI, 29% for heart failure, and 27% for stroke, the AHRQ noted.

Since “death following discharge from a hospital is not reflected in these data,” the report said, measures of inpatient mortality “can reflect both improvements in health care and shifts in where end-of-life care takes place over time.”

The estimates in the report are based on data from the Nationwide Inpatient Sample (2002-2011) and State Inpatient Databases (2012).¹

Timely Epinephrine for Pediatric In-Hospital Cardiac Arrest

BY MARY ANN MOON
FROM JAMA

Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published in JAMA.¹

For the approximately 16,000 US children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.

“It is highly unlikely that any such study will ever be done, given the ethical considerations; so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period,” said Dr Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts and the department of anesthesiology at Aarhus (Denmark) University and his associates.¹

All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.

Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (RR, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).

In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr Andersen and his associates said.

These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.

ED Care Pathway Hastens Febrile Neutropenia Therapy

BY Kari Oakes
FROM THE JOURNAL OF ONCOLOGY PRACTICE

Cancer patients who arrive in the ED with febrile neutropenia (FN) received antibiotics much more quickly when their condition was identified as a medical emergency and a care pathway was used to guide treatment. The set of simple interventions slashed average time to antibiotics from about 4 hours to less than 1.5 hours, compared with a historical cohort, and the inexpensive interventions have had durable results.

Dr Michael Keng and his coinvestigators at the Cleveland Clinic reported the results of a single-center prospective analysis that targeted FN, a common and serious chemotherapy complication with a mortality rate that can exceed 50% in medically fragile individuals.¹

“With an increasing number of outpatient chemotherapy regimens, more patients are likely to present to the emergency department with FN,” wrote Dr Keng. The FN pathway devised by Dr Keng and his associates implemented key changes designed to identify FN as an emergency and guide prompt triage, assessment, and treatment.

Study coauthor Dr Mikkael Sekeres said, “The interventions were not complicated. We standardized our definition of fever, provided patients with wallet-sized cards alerting emergency departments to the potential of this serious condition, worked with our emergency department staff to change the triage level of fever and neutropenia to be equivalent to that observed for heart attack or stroke, designed standard febrile neutropenia order sets for our electronic medical record, and relocated the antibiotics used to treat febrile neutropenia to our emergency department.”

Febrile patients with cancer in the prospective cohort (n = 223) were compared with a historical cohort of patients presenting to the ED who received usual care (n = 87), as well as to a concurrent cohort of patients who were directly admitted to the hospital (n = 114). The total number of FN episodes for the cohorts was 276, 107, and 114, respectively. Multivariable analysis was used to account for some differences in patient characteristics across cohorts.

Using the order set in the electronic health record (EHR) also made a difference: for those treated per the order set (n = 103), median time to antibiotics was 68 minutes, compared with 96 minutes when the order set was not used.

Secondary outcome measures included times to physician assessment, blood draw, and antibiotic order placement. All measures except time to physician assessment were significantly shorter for the FN pathway group than for the comparison cohorts (P<.001 for all).

Since so many changes were made at once, Dr Keng and his coauthors noted, “It is difficult to determine the impact of any one change.” Some institutions may have difficulty implementing all the interventions, but immediate triage, automated antibiotic ordering, and EHR use were the changes that had the most impact, he wrote.

“Instituting these changes took less than half a year, and the benefits have persisted for years afterward,” Dr Sekeres said in an interview.

ESC: Aldosterone Blockade Fails to Fly for Early MI in ALBATROSS

BY BRUCE JANCIN
AT THE European Society of Cardiology CONGRESS 2015

LONDON – Aldosterone blockade with oral spironolactone showed a disappointing lack of clinical benefit when initiated in the first hours after an acute MI without heart failure in the large, randomized ALBATROSS trial.

ALBATROSS did, however, flash a silver lining under one wing: A whopping 80% reduction in 6-month mortality in a prespecified subgroup analysis restricted to the 1,229 participants with ST-elevation MI, Dr Gilles Montalescot reported at the annual congress of the European Society of Cardiology.

Although this finding is intriguing, hypothesis-generating, and definitely warrants a confirmatory study, he continued, mortality was nevertheless merely a secondary endpoint in ALBATROSS.

In contrast, the primary composite outcome was negative, so the takeaway message is clear: “The results of the ALBATROSS study do not warrant the extension of aldosterone blockade to MI patients without heart failure,” said Dr Montalescot, professor of cardiology at the University of Paris.

ALBATROSS was a multicenter French trial that randomly assigned 1,603 acute MI patients to standard therapy alone or with added mineralocorticoid antagonist therapy started within the first 2 days of their coronary event. Often the aldosterone antagonist was begun in the ambulance en route to the hospital.¹

The primary endpoint was a composite of death, resuscitated cardiac arrest, ventricular fibrillation or tachycardia, heart failure, or an indication for an implantable cardioverter defibrillator. There were 194 such events, and they occurred at a similar rate in the patients who got 25 mg/day of spironolactone and those who did not.

The rationale for ALBATROSS was sound, according to the cardiologist. Aldosterone is a stress hormone released in acute MI. It has deleterious cardiac effects, including arrhythmias, heart failure, and a dose-dependent increase in mortality, so it makes good sense to block it as soon as possible in MI patients. In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, the aldosterone antagonist eplerenone, when started 3-14 days post MI in patients with early heart failure, significantly reduced mortality,² with the bulk of the benefit occurring in patients in whom the drug was started 3-7 days post MI.

Last year, Dr Montalescot and his coinvestigators published the Randomized, Placebo-Controlled Trial Evaluating The Safety and Efficacy of Early Treatment With Eplerenone in Patients With Acute Myocardial Infarction (REMINDER) study, in which 1,012 ST-elevation MI (STEMI) patients without heart failure were randomized to eplerenone or placebo within the first 24 hours. The study showed a significant reduction in levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP in the eplerenone arm,² but that’s not a clinical endpoint. ALBATROSS was the first study to look at the clinical impact of commencing mineralocorticoid antagonist therapy prior to day 3 post-MI.

Discussant Dr John McMurray, professor of cardiology at the University of Glasgow, Scotland, said that ALBATROSS was simply underpowered and thus leaves unanswered the clinically important question of whether early initiation of aldosterone blockade post MI in patients without heart failure confers clinical benefit. The investigators projected a total of 269 events in the composite endpoint but got only 194 because the study participants were so well treated and contemporary medical and interventional therapies are quite effective. 

He dismissed the sharp reduction seen in 6-month mortality with spironolactone in the STEMI patients as “just implausible—we don’t know of any treatments in medicine that reduce mortality by 80%.”

Noting that there were only 28 deaths in the study, Dr McMurray asserted that “a subgroup analysis on such a small number of events is never going to give you a reliable result.” Moreover, he added, “subgroup analysis is even more treacherous when the overall trial is underpowered.”

Dr Montalescot replied that, while he considers the signal of a mortality benefit for aldosterone blockade in STEMI patients worthy of pursuit in a large randomized trial, the prospects for mounting such a study are poor. The medications are now available as generics, so there is no commercial incentive. The French Ministry of Health, which funded ALBATROSS, isn’t prepared to back a follow-up study. The best hope is that eventually one of the pharmaceutical companies developing third-generation aldosterone antagonists, now in phase II studies, will become interested, he said.

Dr Montalescot said that, while he receives research grants and consulting fees from numerous pharmaceutical companies, these commercial relationships aren’t relevant to the government-funded ALBATROSS trial.

Inpatient Mortality Down for High-Volume Conditions

BY RICHARD FRANKI
Frontline Medical News

Over that period, mortality among adults hospitalized with pneumonia went from 65 per 1,000 admissions to 35.8 per 1,000 for a drop of 45%—the largest of the four high-volume conditions. Corresponding declines for the others were 41% for acute MI, 29% for heart failure, and 27% for stroke, the AHRQ noted.

Since “death following discharge from a hospital is not reflected in these data,” the report said, measures of inpatient mortality “can reflect both improvements in health care and shifts in where end-of-life care takes place over time.”

The estimates in the report are based on data from the Nationwide Inpatient Sample (2002-2011) and State Inpatient Databases (2012).¹

Three lab tests predict serious bacterial infections in infants

BY JENNIE SMITH
AT SAEM 2015

SAN DIEGO – A simple three-variable prediction rule can accurately predict which febrile infants younger than age 2 months with fever who present to the ED have serious bacterial infections. Bacterial meningitis, urinary tract infections, and bacteremia are considered serious bacterial infections; many young infants with these infections are difficult to identify, and current laboratory protocols for identifying them include urinalysis, white blood cell counts, band counts, and sometimes cerebrospinal fluid.

In a presentation at the annual meeting of the Society for Academic Emergency Medicine, Dr Nathan Kuppermann of the University of California, Davis, demonstrated results from a large prospective cohort study of 1,821 febrile infants 60 days old and younger conducted at 21 EDs. Infants with underlying congenital anomalies or critical illness were excluded from the study.

The investigators evaluated 8 variables as potential predictors: age, temperature, Yale Observation Scale score, and clinician suspicion of SBI, along with 4 laboratory variables (urinalysis, white blood cell count, absolute neutrophil count [ANC], and procalcitonin). Band counts were available at some, but not all of the study centers, and therefore were not evaluated.

Dr Kuppermann and his colleagues found that positive urinalysis, ANC of 4.09 x 1,000/mm3 or higher, and serum procalcitonin of 1.71 ng/mL or higher were, taken together, 98% to 99% sensitive and about 60% specific, in predicting SBI in the cohort. Negative predictive values approached 100%. The rate of SBI was 9.3% of the cohort, in keeping with expected rates.

“The SBI positive group was more likely to have higher clinician suspicion of SBI, and all of the lab markers were more elevated in the SBI positive group than the SBI negative group,” Dr Kuppermann said at the meeting. However, after the researchers considered all of the predictors as a group, only the urinalysis, the ANC, and the procalcitonin remained important. Only 3 of 1,821 (0.2%) infants with SBIs were missed when the three-variable prediction tool was used.

To make the prediction rule easier to remember and use, the investigators evaluated lower, more standard, and easier to remember thresholds for the three variables. They reanalyzed their data using a lower cutoff point for ANC of 4.00 x 1,000/mm3, and a lowered procalcitonin cutoff of 0.5 ng/mL. The rule performed almost identically as the original rule, and did not miss any more patients with SBIs beyond the original three.

cleanfotos/Shutterstock

Dr Kuppermann described the three-variable rule as “simple, objective, and highly accurate” in predicting or ruling out SBI. Nonetheless, it requires external validation in a large cohort, he acknowledged. He said he would continue to routinely perform lumbar punctures in infants younger than 30 days with fever until the findings could be further validated.

“But personally, in that second month of life, I would use these data to decide who actually needs a lumbar puncture and hospitalization,” he said. 

Dr Kuppermann also noted as a limitation of the study that the cohort included few infants with bacterial meningitis.

ED revisits twice as frequent as expected

BY MARY ANN MOON
FROM ANNALS OF INTERNAL MEDICINE

The rate of adult revisits to EDs is more than twice as high as has been reported previously – 8% at 3 days and 20% at 30 days – in large part because until now researchers have failed to account for revisits to different hospitals, according to a report published online June 2 in Annals of Internal Medicine.

Little is known about returns to an emergency department following an index ED visit because most studies have assessed only visits to a single institution or to hospitals within a single state or insurance plan. Now researchers have performed a broader examination of the issue by analyzing newly available multistate longitudinal data from the Healthcare Cost and Utilization Project, which allowed them to identify returns to any ED or acute-care hospital. They focused on acute-care revisits after 57,530,239 initial ED visits by adults in six states (Arizona, California, Florida, Nebraska, Utah, and Hawaii) during 2006-2010.

At 3 days after an initial ED visit, the overall revisit rate was 8.2%, with one-third of these revisits occurring at a medical facility different from that of the initial visit. Previously, estimates of 3-day revisits have ranged from 2.7% to 3.4%. At 30 days, the revisit rate was 20%, and approximately one-third of these revisits involved a different facility. Revisits to different institutions “may have special clinical and financial implications because fragmentation of care increases the likelihood of duplication of services and problems with care transitions,” said Dr Reena Duseja of the department of emergency medicine, University of California, San Francisco, and her associates.

“The scope of revisits to outside institutions is much greater than previously suspected, which suggests that improving communication infrastructure across institutions (such as health information exchanges) may improve care and allow individual institutions to get a more accurate picture of their revisit rates,” they noted (Ann Intern Med. 2015;162(11):750-756.  doi:10.7326/M14-1616).

Revisit rates varied substantially according to diagnosis. “Skin and subcutaneous tissue infection” accounted for 23% of revisits. “Abdominal pain” was the diagnosis with the next highest revisit rate (10%). The most frequent diagnosis among patients who revisited a different hospital was back pain (2.6%), and nonspecific chest pain was the diagnosis with the 

highest rate of later admission to a different hospital (1.1%).

Africa Studio/Shutterstock

“Financial data from the Florida facilities showed that revisits accounted for more of the total costs of ED care than initial visits did. This demonstrates that revisits are a major, and unaccounted for, component of emergency care costs,” Dr Duseja and her associates said.

Because of insufficient data, they could not determine whether these revisits reflected inadequate access to primary care, patient nonadherence to treatment recommendations, poor quality of care at the initial visit, or other factors, the researchers noted.

Cefazolin ranks sixth as cause of drug-induced liver injury

BY AMY KARON

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

“Cephalosporins have been reported as rare causes of DILI, but most data come from single case reports,” the researchers said. To study causes of DILI, they analyzed cases from the Drug-Induced Livery Injury Network, an ongoing prospective study at 8 US medical centers. Enrolled patients had strong clinical suspicion for liver injury caused by a drug or an herbal agent. Liver injury was defined based on specific criteria for liver enzymes, alkaline phosphatase (ALP), or total bilirubin levels, or as an international normalized ratio greater than 1.5 that was accompanied by elevated liver enzymes or ALP. Patients were followed for at least 6 months after their baseline visit (Clin Gastroenterol Hepatol. Published January 26, 2015. doi: 10.1016/j.cgh.2015.01.010).

Among the 1,212 cases of DILI in the analysis, one-third were linked to antimicrobial therapies, including 41 (3.3%) in which cephalosporins were implicated, the investigators reported. Nineteen of the cases were tied to a single dose of intravenous cefazolin given before surgery. These patients developed cholestatic or mixed hepatocellular-cholestatic injury 1 to 3 weeks after the cefazolin infusion. They almost always had jaundice and pruritus, and usually also had fever and nausea. Signs and symptoms were self-limiting, resolving within a few days to a few weeks.

“Because of confusion about the specific diagnosis, patients underwent substantial diagnostic testing (including multiple computed tomography scans, magnetic resonance imaging scans, endoscopic retrograde cholangiopancreatography exams, liver biopsies, and others), which often were unnecessary, and in some cases led to severe complications,” the investigators said.

“The study also identified barriers to identifying cefazolin as a cause of DILI,” they said. Patients often did not know they had received the antibiotic, and clinicians, including study investigators, often did not know that cefazolin could cause DILI. In more than half of cases, DILI was linked to cefazolin only after careful medical record reviews. “For these reasons, we speculate that cefazolin is and has been underappreciated as a cause of DILI,” the researchers noted. “The appearance of jaundice and pruritus 1 to 3 weeks after minor surgery should lead to a search of surgical records and medications that might have been given during surgery. These results also imply that the merits of routine use of cefazolin at the time of uncomplicated surgery should be reconsidered carefully.”

PC-PROD/Shutterstock

“Two patients died after receiving cephalosporins other than cefazolin, and another patient developed severe liver injury,” the researchers said. “However, in each of the fatal cases, patients had a complicated clinical course, with a severe hypersensitivity reaction on top of an underlying liver disease. Therefore, we urge caution in concluding that non-cefazolin cephalosporin-induced DILI may be severe or fatal,” they said. “Because cephalosporins are used commonly in clinical practice, it is likely that the overall mortality rate associated with cephalosporin use is low, but not nil, and it may be more likely in patients with underlying disorders.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the National Cancer Institute, and by six Clinical and Translational Science Award grants. The investigators reported having no conflicts of interest.

Pelvic CT may not be needed to diagnose intra-abdominal injury in children

BY JENNIE SMITH

FROM SAEM 2015

But concerns about excess exposure to CT radiation, particularly to the gonads, led one group of researchers to question whether it’s necessary to scan the entire abdominopelvic region in all of these patients to identify IAI.

Dr Stacy Reynolds and her colleagues at the Carolinas Medical Center in Charlotte, North Carolina, hypothesized that CT limited to the radiographic abdomen – the region between the dome of the diaphragm to the top of the iliac crest – can capture the vast majority of IAIs in this population.

At the Society for Academic Emergency Medicine annual meeting, Dr Reynolds presented results from a retrospective cohort study enrolling 313 hemodynamically stable pediatric patients (median age 14 years, 64% male) presenting to 12 EDs after blunt trauma. Patients with known pelvic fractures or hip dislocation were excluded, as they would have had a clear indication for a full abdominopelvic CT.

All subjects underwent axial abdominopelvic CT imaging. Researchers created matched pairs of images comprising the original scans and those that had been altered with software that truncated the pelvic portion of the study to create CT abdomen-only studies. Study radiologists were blinded to the results of the original scans.

In all, 26 IAI’s were diagnosed in 24 patients: 8 hepatic injuries, 12 splenic injuries, 5 renal injuries, and 1 retroperitoneal hemorrhage. Abdominal CT alone was 85% sensitive (95% CI, 65%-96%) and 99% specific (95% CI, 97%-100%) in identifying IAIs. The four missed injuries were solid organ injuries within the radiographic abdomen. False positives occurred in two of the complete scans, both involving free fluid prompting suspicion of small bowel injury later ruled out by clinical observation.

Dr Reynolds said in an interview that the findings, while promising, were limited by the study’s small numbers, and its use of axial images alone, when sagittal images also would be required for the most accurate diagnoses. Also, physician suspicion of IAI prior to imaging was not captured because of the study’s retrospective design, she said. “The real key to whether or not this hypothesis is valuable is if physicians are able to target the right population of patients for application.”

Dr Reynolds cautioned that the findings would need to be validated in a larger trial before any changes could be made to clinical practice. “Some of the outcomes that we need to make sure whether we’re missing are still rare,” she said. “You couldn’t feel confident that this is the right way to go with a study this small, but it establishes that we can safely and ethically pursue a multicenter trial that would examine the issue with bigger numbers.”

Other groups of investigators, including members of the Pediatric Emergency Care Applied Research Network (PECARN), also have taken up the question of identifying children at low risk of IAI who may not need CT screening after blunt trauma. In 2013, PECARN published a prediction rule using only patient history and physical examination findings intended to obviate use of CT in the lowest-risk patients (Ann Emerg Med. 2013;62:107-116.e2).

Dr Reynolds said that while overuse of CT was a worrisome trend that could have long-term implications for patients, and that it was important to identify ways it might be limited, there is a reason it remains the go-to technology in the ED for detecting IAI. “It’s got very high sensitivity and specificity. If you’re a busy trauma surgeon who’s admitting 20 injured patients in a night, there’s no faster or more efficient way to determine whether the patient in front of you is injured.”

The ‘sad truth’ about suicide risk assessment scales

BY BRUCE JANCIN

EXPERT ANALYSIS FROM THE ANNUAL AAS CONFERENCE

ATLANTA – “Don’t – repeat, don’t – use risk assessment tools and scales in an effort to predict future suicide in patients who’ve committed intentional self-harm,” Dr Keith Hawton urged at the annual conference of the American Association of Suicidology.

He noted this isn’t simply a matter of his personal opinion; it’s also a strongly worded recommendation in the current UK NICE (National Institute for Health and Care Excellence) guidelines on the long-term management of patients who’ve committed self-harm. The various NICE guidelines, which address numerous areas of medical practice and are used to determine what’s reimbursable through the UK’s National Health Service, are famously evidence based and concerned with cost-effectiveness.

The NICE guidelines on management of self-harm further advise: “Do not use risk assessment tools and scales to determine who should and should not be offered treatment or who should be discharged from hospital.”

“Those are some fairly contentious statements about risk assessment scales. But those statements are based upon review of the evidence about the effectiveness of risk assessment scales,” according to Dr Hawton, professor of psychiatry and director of the Centre for Suicide Research at the University of Oxford (England).

Zhiltsov Alexandr/Shutterstock

“In our country, hospitals have become obsessed with risk assessment. And usually, it seems to be about protecting the organization rather than the patient, because so often the results aren’t linked to risk management, which is what we should be talking about,” he observed.

Dr Hawton and his colleagues provided some of the evidence that led to the NICE guideline committee’s thumbs-down on the use of suicide risk assessment scales in patients who’ve engaged in intentional self-harm. In a study provocatively titled “The sad truth about the SADPERSONS scale,” he and his coinvestigators essentially dismantled SADPERSONS, a widely used screening tool for suicide risk, concluding that it is without value.

The acronym stands for Sex (male), Age (<19 or >45), Depression, Previous attempts, Ethanol abuse, Rational thinking loss, Social supports lacking, Organized plan, No spouse, and Sickness. One point is given for each. Patients who score 7-10 are to be hospitalized, and those with a total of 5 or 6 points should be strongly considered for hospitalization.

Dr Hawton and coinvestigators tracked 126 consecutive patients who were evaluated for self-harm using the SADPERSONS scale in a general hospital emergency department and then followed them for 6 months. SADPERSONS performed miserably in predicting clinical management outcomes, such as admission to a psychiatric hospital or repetition of self-harm within 6 months. Indeed, the test failed to identify 4 of the 5 patients admitted to a psychiatric hospital, 65 of 70 who were referred from the ED to community psychiatric aftercare, and 28 of 31 who repeated self-harm within 6 months. Thus, its sensitivity as a predictor of repetition of self-harm was a lowly 6.6% (Emerg Med J. 2014;31:796-798).

And yet, a 32-hospital UK national study conducted by Dr Hawton and others found that SADPERSONS was the most widely used scale in EDs for risk assessment following self-harm (BMJ Open. 2014;4(5):e004732. doi:10.1136/bmjopen-2013-004732). “It’s a very crude tool,” Dr Hawton said. “How it found its way into common use in clinical practice is beyond me.”

[email protected] 

Three lab tests predict serious bacterial infections in infants

BY JENNIE SMITH
AT SAEM 2015

SAN DIEGO – A simple three-variable prediction rule can accurately predict which febrile infants younger than age 2 months with fever who present to the ED have serious bacterial infections. Bacterial meningitis, urinary tract infections, and bacteremia are considered serious bacterial infections; many young infants with these infections are difficult to identify, and current laboratory protocols for identifying them include urinalysis, white blood cell counts, band counts, and sometimes cerebrospinal fluid.

In a presentation at the annual meeting of the Society for Academic Emergency Medicine, Dr Nathan Kuppermann of the University of California, Davis, demonstrated results from a large prospective cohort study of 1,821 febrile infants 60 days old and younger conducted at 21 EDs. Infants with underlying congenital anomalies or critical illness were excluded from the study.

The investigators evaluated 8 variables as potential predictors: age, temperature, Yale Observation Scale score, and clinician suspicion of SBI, along with 4 laboratory variables (urinalysis, white blood cell count, absolute neutrophil count [ANC], and procalcitonin). Band counts were available at some, but not all of the study centers, and therefore were not evaluated.

Dr Kuppermann and his colleagues found that positive urinalysis, ANC of 4.09 x 1,000/mm3 or higher, and serum procalcitonin of 1.71 ng/mL or higher were, taken together, 98% to 99% sensitive and about 60% specific, in predicting SBI in the cohort. Negative predictive values approached 100%. The rate of SBI was 9.3% of the cohort, in keeping with expected rates.

“The SBI positive group was more likely to have higher clinician suspicion of SBI, and all of the lab markers were more elevated in the SBI positive group than the SBI negative group,” Dr Kuppermann said at the meeting. However, after the researchers considered all of the predictors as a group, only the urinalysis, the ANC, and the procalcitonin remained important. Only 3 of 1,821 (0.2%) infants with SBIs were missed when the three-variable prediction tool was used.

To make the prediction rule easier to remember and use, the investigators evaluated lower, more standard, and easier to remember thresholds for the three variables. They reanalyzed their data using a lower cutoff point for ANC of 4.00 x 1,000/mm3, and a lowered procalcitonin cutoff of 0.5 ng/mL. The rule performed almost identically as the original rule, and did not miss any more patients with SBIs beyond the original three.

cleanfotos/Shutterstock

Dr Kuppermann described the three-variable rule as “simple, objective, and highly accurate” in predicting or ruling out SBI. Nonetheless, it requires external validation in a large cohort, he acknowledged. He said he would continue to routinely perform lumbar punctures in infants younger than 30 days with fever until the findings could be further validated.

“But personally, in that second month of life, I would use these data to decide who actually needs a lumbar puncture and hospitalization,” he said. 

Dr Kuppermann also noted as a limitation of the study that the cohort included few infants with bacterial meningitis.

ED revisits twice as frequent as expected

BY MARY ANN MOON
FROM ANNALS OF INTERNAL MEDICINE

The rate of adult revisits to EDs is more than twice as high as has been reported previously – 8% at 3 days and 20% at 30 days – in large part because until now researchers have failed to account for revisits to different hospitals, according to a report published online June 2 in Annals of Internal Medicine.

Little is known about returns to an emergency department following an index ED visit because most studies have assessed only visits to a single institution or to hospitals within a single state or insurance plan. Now researchers have performed a broader examination of the issue by analyzing newly available multistate longitudinal data from the Healthcare Cost and Utilization Project, which allowed them to identify returns to any ED or acute-care hospital. They focused on acute-care revisits after 57,530,239 initial ED visits by adults in six states (Arizona, California, Florida, Nebraska, Utah, and Hawaii) during 2006-2010.

At 3 days after an initial ED visit, the overall revisit rate was 8.2%, with one-third of these revisits occurring at a medical facility different from that of the initial visit. Previously, estimates of 3-day revisits have ranged from 2.7% to 3.4%. At 30 days, the revisit rate was 20%, and approximately one-third of these revisits involved a different facility. Revisits to different institutions “may have special clinical and financial implications because fragmentation of care increases the likelihood of duplication of services and problems with care transitions,” said Dr Reena Duseja of the department of emergency medicine, University of California, San Francisco, and her associates.

“The scope of revisits to outside institutions is much greater than previously suspected, which suggests that improving communication infrastructure across institutions (such as health information exchanges) may improve care and allow individual institutions to get a more accurate picture of their revisit rates,” they noted (Ann Intern Med. 2015;162(11):750-756.  doi:10.7326/M14-1616).

Revisit rates varied substantially according to diagnosis. “Skin and subcutaneous tissue infection” accounted for 23% of revisits. “Abdominal pain” was the diagnosis with the next highest revisit rate (10%). The most frequent diagnosis among patients who revisited a different hospital was back pain (2.6%), and nonspecific chest pain was the diagnosis with the 

highest rate of later admission to a different hospital (1.1%).

Africa Studio/Shutterstock

“Financial data from the Florida facilities showed that revisits accounted for more of the total costs of ED care than initial visits did. This demonstrates that revisits are a major, and unaccounted for, component of emergency care costs,” Dr Duseja and her associates said.

Because of insufficient data, they could not determine whether these revisits reflected inadequate access to primary care, patient nonadherence to treatment recommendations, poor quality of care at the initial visit, or other factors, the researchers noted.

Cefazolin ranks sixth as cause of drug-induced liver injury

BY AMY KARON

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

“Cephalosporins have been reported as rare causes of DILI, but most data come from single case reports,” the researchers said. To study causes of DILI, they analyzed cases from the Drug-Induced Livery Injury Network, an ongoing prospective study at 8 US medical centers. Enrolled patients had strong clinical suspicion for liver injury caused by a drug or an herbal agent. Liver injury was defined based on specific criteria for liver enzymes, alkaline phosphatase (ALP), or total bilirubin levels, or as an international normalized ratio greater than 1.5 that was accompanied by elevated liver enzymes or ALP. Patients were followed for at least 6 months after their baseline visit (Clin Gastroenterol Hepatol. Published January 26, 2015. doi: 10.1016/j.cgh.2015.01.010).

Among the 1,212 cases of DILI in the analysis, one-third were linked to antimicrobial therapies, including 41 (3.3%) in which cephalosporins were implicated, the investigators reported. Nineteen of the cases were tied to a single dose of intravenous cefazolin given before surgery. These patients developed cholestatic or mixed hepatocellular-cholestatic injury 1 to 3 weeks after the cefazolin infusion. They almost always had jaundice and pruritus, and usually also had fever and nausea. Signs and symptoms were self-limiting, resolving within a few days to a few weeks.

“Because of confusion about the specific diagnosis, patients underwent substantial diagnostic testing (including multiple computed tomography scans, magnetic resonance imaging scans, endoscopic retrograde cholangiopancreatography exams, liver biopsies, and others), which often were unnecessary, and in some cases led to severe complications,” the investigators said.

“The study also identified barriers to identifying cefazolin as a cause of DILI,” they said. Patients often did not know they had received the antibiotic, and clinicians, including study investigators, often did not know that cefazolin could cause DILI. In more than half of cases, DILI was linked to cefazolin only after careful medical record reviews. “For these reasons, we speculate that cefazolin is and has been underappreciated as a cause of DILI,” the researchers noted. “The appearance of jaundice and pruritus 1 to 3 weeks after minor surgery should lead to a search of surgical records and medications that might have been given during surgery. These results also imply that the merits of routine use of cefazolin at the time of uncomplicated surgery should be reconsidered carefully.”

PC-PROD/Shutterstock

“Two patients died after receiving cephalosporins other than cefazolin, and another patient developed severe liver injury,” the researchers said. “However, in each of the fatal cases, patients had a complicated clinical course, with a severe hypersensitivity reaction on top of an underlying liver disease. Therefore, we urge caution in concluding that non-cefazolin cephalosporin-induced DILI may be severe or fatal,” they said. “Because cephalosporins are used commonly in clinical practice, it is likely that the overall mortality rate associated with cephalosporin use is low, but not nil, and it may be more likely in patients with underlying disorders.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the National Cancer Institute, and by six Clinical and Translational Science Award grants. The investigators reported having no conflicts of interest.

Pelvic CT may not be needed to diagnose intra-abdominal injury in children

BY JENNIE SMITH

FROM SAEM 2015

But concerns about excess exposure to CT radiation, particularly to the gonads, led one group of researchers to question whether it’s necessary to scan the entire abdominopelvic region in all of these patients to identify IAI.

Dr Stacy Reynolds and her colleagues at the Carolinas Medical Center in Charlotte, North Carolina, hypothesized that CT limited to the radiographic abdomen – the region between the dome of the diaphragm to the top of the iliac crest – can capture the vast majority of IAIs in this population.

At the Society for Academic Emergency Medicine annual meeting, Dr Reynolds presented results from a retrospective cohort study enrolling 313 hemodynamically stable pediatric patients (median age 14 years, 64% male) presenting to 12 EDs after blunt trauma. Patients with known pelvic fractures or hip dislocation were excluded, as they would have had a clear indication for a full abdominopelvic CT.

All subjects underwent axial abdominopelvic CT imaging. Researchers created matched pairs of images comprising the original scans and those that had been altered with software that truncated the pelvic portion of the study to create CT abdomen-only studies. Study radiologists were blinded to the results of the original scans.

In all, 26 IAI’s were diagnosed in 24 patients: 8 hepatic injuries, 12 splenic injuries, 5 renal injuries, and 1 retroperitoneal hemorrhage. Abdominal CT alone was 85% sensitive (95% CI, 65%-96%) and 99% specific (95% CI, 97%-100%) in identifying IAIs. The four missed injuries were solid organ injuries within the radiographic abdomen. False positives occurred in two of the complete scans, both involving free fluid prompting suspicion of small bowel injury later ruled out by clinical observation.

Dr Reynolds said in an interview that the findings, while promising, were limited by the study’s small numbers, and its use of axial images alone, when sagittal images also would be required for the most accurate diagnoses. Also, physician suspicion of IAI prior to imaging was not captured because of the study’s retrospective design, she said. “The real key to whether or not this hypothesis is valuable is if physicians are able to target the right population of patients for application.”

Dr Reynolds cautioned that the findings would need to be validated in a larger trial before any changes could be made to clinical practice. “Some of the outcomes that we need to make sure whether we’re missing are still rare,” she said. “You couldn’t feel confident that this is the right way to go with a study this small, but it establishes that we can safely and ethically pursue a multicenter trial that would examine the issue with bigger numbers.”

Other groups of investigators, including members of the Pediatric Emergency Care Applied Research Network (PECARN), also have taken up the question of identifying children at low risk of IAI who may not need CT screening after blunt trauma. In 2013, PECARN published a prediction rule using only patient history and physical examination findings intended to obviate use of CT in the lowest-risk patients (Ann Emerg Med. 2013;62:107-116.e2).

Dr Reynolds said that while overuse of CT was a worrisome trend that could have long-term implications for patients, and that it was important to identify ways it might be limited, there is a reason it remains the go-to technology in the ED for detecting IAI. “It’s got very high sensitivity and specificity. If you’re a busy trauma surgeon who’s admitting 20 injured patients in a night, there’s no faster or more efficient way to determine whether the patient in front of you is injured.”

The ‘sad truth’ about suicide risk assessment scales

BY BRUCE JANCIN

EXPERT ANALYSIS FROM THE ANNUAL AAS CONFERENCE

ATLANTA – “Don’t – repeat, don’t – use risk assessment tools and scales in an effort to predict future suicide in patients who’ve committed intentional self-harm,” Dr Keith Hawton urged at the annual conference of the American Association of Suicidology.

He noted this isn’t simply a matter of his personal opinion; it’s also a strongly worded recommendation in the current UK NICE (National Institute for Health and Care Excellence) guidelines on the long-term management of patients who’ve committed self-harm. The various NICE guidelines, which address numerous areas of medical practice and are used to determine what’s reimbursable through the UK’s National Health Service, are famously evidence based and concerned with cost-effectiveness.

The NICE guidelines on management of self-harm further advise: “Do not use risk assessment tools and scales to determine who should and should not be offered treatment or who should be discharged from hospital.”

“Those are some fairly contentious statements about risk assessment scales. But those statements are based upon review of the evidence about the effectiveness of risk assessment scales,” according to Dr Hawton, professor of psychiatry and director of the Centre for Suicide Research at the University of Oxford (England).

Zhiltsov Alexandr/Shutterstock

“In our country, hospitals have become obsessed with risk assessment. And usually, it seems to be about protecting the organization rather than the patient, because so often the results aren’t linked to risk management, which is what we should be talking about,” he observed.

Dr Hawton and his colleagues provided some of the evidence that led to the NICE guideline committee’s thumbs-down on the use of suicide risk assessment scales in patients who’ve engaged in intentional self-harm. In a study provocatively titled “The sad truth about the SADPERSONS scale,” he and his coinvestigators essentially dismantled SADPERSONS, a widely used screening tool for suicide risk, concluding that it is without value.

The acronym stands for Sex (male), Age (<19 or >45), Depression, Previous attempts, Ethanol abuse, Rational thinking loss, Social supports lacking, Organized plan, No spouse, and Sickness. One point is given for each. Patients who score 7-10 are to be hospitalized, and those with a total of 5 or 6 points should be strongly considered for hospitalization.

Dr Hawton and coinvestigators tracked 126 consecutive patients who were evaluated for self-harm using the SADPERSONS scale in a general hospital emergency department and then followed them for 6 months. SADPERSONS performed miserably in predicting clinical management outcomes, such as admission to a psychiatric hospital or repetition of self-harm within 6 months. Indeed, the test failed to identify 4 of the 5 patients admitted to a psychiatric hospital, 65 of 70 who were referred from the ED to community psychiatric aftercare, and 28 of 31 who repeated self-harm within 6 months. Thus, its sensitivity as a predictor of repetition of self-harm was a lowly 6.6% (Emerg Med J. 2014;31:796-798).

And yet, a 32-hospital UK national study conducted by Dr Hawton and others found that SADPERSONS was the most widely used scale in EDs for risk assessment following self-harm (BMJ Open. 2014;4(5):e004732. doi:10.1136/bmjopen-2013-004732). “It’s a very crude tool,” Dr Hawton said. “How it found its way into common use in clinical practice is beyond me.”

[email protected] 

Three lab tests predict serious bacterial infections in infants

BY JENNIE SMITH
AT SAEM 2015

SAN DIEGO – A simple three-variable prediction rule can accurately predict which febrile infants younger than age 2 months with fever who present to the ED have serious bacterial infections. Bacterial meningitis, urinary tract infections, and bacteremia are considered serious bacterial infections; many young infants with these infections are difficult to identify, and current laboratory protocols for identifying them include urinalysis, white blood cell counts, band counts, and sometimes cerebrospinal fluid.

In a presentation at the annual meeting of the Society for Academic Emergency Medicine, Dr Nathan Kuppermann of the University of California, Davis, demonstrated results from a large prospective cohort study of 1,821 febrile infants 60 days old and younger conducted at 21 EDs. Infants with underlying congenital anomalies or critical illness were excluded from the study.

The investigators evaluated 8 variables as potential predictors: age, temperature, Yale Observation Scale score, and clinician suspicion of SBI, along with 4 laboratory variables (urinalysis, white blood cell count, absolute neutrophil count [ANC], and procalcitonin). Band counts were available at some, but not all of the study centers, and therefore were not evaluated.

Dr Kuppermann and his colleagues found that positive urinalysis, ANC of 4.09 x 1,000/mm3 or higher, and serum procalcitonin of 1.71 ng/mL or higher were, taken together, 98% to 99% sensitive and about 60% specific, in predicting SBI in the cohort. Negative predictive values approached 100%. The rate of SBI was 9.3% of the cohort, in keeping with expected rates.

“The SBI positive group was more likely to have higher clinician suspicion of SBI, and all of the lab markers were more elevated in the SBI positive group than the SBI negative group,” Dr Kuppermann said at the meeting. However, after the researchers considered all of the predictors as a group, only the urinalysis, the ANC, and the procalcitonin remained important. Only 3 of 1,821 (0.2%) infants with SBIs were missed when the three-variable prediction tool was used.

To make the prediction rule easier to remember and use, the investigators evaluated lower, more standard, and easier to remember thresholds for the three variables. They reanalyzed their data using a lower cutoff point for ANC of 4.00 x 1,000/mm3, and a lowered procalcitonin cutoff of 0.5 ng/mL. The rule performed almost identically as the original rule, and did not miss any more patients with SBIs beyond the original three.

cleanfotos/Shutterstock

Dr Kuppermann described the three-variable rule as “simple, objective, and highly accurate” in predicting or ruling out SBI. Nonetheless, it requires external validation in a large cohort, he acknowledged. He said he would continue to routinely perform lumbar punctures in infants younger than 30 days with fever until the findings could be further validated.

“But personally, in that second month of life, I would use these data to decide who actually needs a lumbar puncture and hospitalization,” he said. 

Dr Kuppermann also noted as a limitation of the study that the cohort included few infants with bacterial meningitis.

ED revisits twice as frequent as expected

BY MARY ANN MOON
FROM ANNALS OF INTERNAL MEDICINE

The rate of adult revisits to EDs is more than twice as high as has been reported previously – 8% at 3 days and 20% at 30 days – in large part because until now researchers have failed to account for revisits to different hospitals, according to a report published online June 2 in Annals of Internal Medicine.

Little is known about returns to an emergency department following an index ED visit because most studies have assessed only visits to a single institution or to hospitals within a single state or insurance plan. Now researchers have performed a broader examination of the issue by analyzing newly available multistate longitudinal data from the Healthcare Cost and Utilization Project, which allowed them to identify returns to any ED or acute-care hospital. They focused on acute-care revisits after 57,530,239 initial ED visits by adults in six states (Arizona, California, Florida, Nebraska, Utah, and Hawaii) during 2006-2010.

At 3 days after an initial ED visit, the overall revisit rate was 8.2%, with one-third of these revisits occurring at a medical facility different from that of the initial visit. Previously, estimates of 3-day revisits have ranged from 2.7% to 3.4%. At 30 days, the revisit rate was 20%, and approximately one-third of these revisits involved a different facility. Revisits to different institutions “may have special clinical and financial implications because fragmentation of care increases the likelihood of duplication of services and problems with care transitions,” said Dr Reena Duseja of the department of emergency medicine, University of California, San Francisco, and her associates.

“The scope of revisits to outside institutions is much greater than previously suspected, which suggests that improving communication infrastructure across institutions (such as health information exchanges) may improve care and allow individual institutions to get a more accurate picture of their revisit rates,” they noted (Ann Intern Med. 2015;162(11):750-756.  doi:10.7326/M14-1616).

Revisit rates varied substantially according to diagnosis. “Skin and subcutaneous tissue infection” accounted for 23% of revisits. “Abdominal pain” was the diagnosis with the next highest revisit rate (10%). The most frequent diagnosis among patients who revisited a different hospital was back pain (2.6%), and nonspecific chest pain was the diagnosis with the 

highest rate of later admission to a different hospital (1.1%).

Africa Studio/Shutterstock

“Financial data from the Florida facilities showed that revisits accounted for more of the total costs of ED care than initial visits did. This demonstrates that revisits are a major, and unaccounted for, component of emergency care costs,” Dr Duseja and her associates said.

Because of insufficient data, they could not determine whether these revisits reflected inadequate access to primary care, patient nonadherence to treatment recommendations, poor quality of care at the initial visit, or other factors, the researchers noted.

Cefazolin ranks sixth as cause of drug-induced liver injury

BY AMY KARON

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

“Cephalosporins have been reported as rare causes of DILI, but most data come from single case reports,” the researchers said. To study causes of DILI, they analyzed cases from the Drug-Induced Livery Injury Network, an ongoing prospective study at 8 US medical centers. Enrolled patients had strong clinical suspicion for liver injury caused by a drug or an herbal agent. Liver injury was defined based on specific criteria for liver enzymes, alkaline phosphatase (ALP), or total bilirubin levels, or as an international normalized ratio greater than 1.5 that was accompanied by elevated liver enzymes or ALP. Patients were followed for at least 6 months after their baseline visit (Clin Gastroenterol Hepatol. Published January 26, 2015. doi: 10.1016/j.cgh.2015.01.010).

Among the 1,212 cases of DILI in the analysis, one-third were linked to antimicrobial therapies, including 41 (3.3%) in which cephalosporins were implicated, the investigators reported. Nineteen of the cases were tied to a single dose of intravenous cefazolin given before surgery. These patients developed cholestatic or mixed hepatocellular-cholestatic injury 1 to 3 weeks after the cefazolin infusion. They almost always had jaundice and pruritus, and usually also had fever and nausea. Signs and symptoms were self-limiting, resolving within a few days to a few weeks.

“Because of confusion about the specific diagnosis, patients underwent substantial diagnostic testing (including multiple computed tomography scans, magnetic resonance imaging scans, endoscopic retrograde cholangiopancreatography exams, liver biopsies, and others), which often were unnecessary, and in some cases led to severe complications,” the investigators said.

“The study also identified barriers to identifying cefazolin as a cause of DILI,” they said. Patients often did not know they had received the antibiotic, and clinicians, including study investigators, often did not know that cefazolin could cause DILI. In more than half of cases, DILI was linked to cefazolin only after careful medical record reviews. “For these reasons, we speculate that cefazolin is and has been underappreciated as a cause of DILI,” the researchers noted. “The appearance of jaundice and pruritus 1 to 3 weeks after minor surgery should lead to a search of surgical records and medications that might have been given during surgery. These results also imply that the merits of routine use of cefazolin at the time of uncomplicated surgery should be reconsidered carefully.”

PC-PROD/Shutterstock

“Two patients died after receiving cephalosporins other than cefazolin, and another patient developed severe liver injury,” the researchers said. “However, in each of the fatal cases, patients had a complicated clinical course, with a severe hypersensitivity reaction on top of an underlying liver disease. Therefore, we urge caution in concluding that non-cefazolin cephalosporin-induced DILI may be severe or fatal,” they said. “Because cephalosporins are used commonly in clinical practice, it is likely that the overall mortality rate associated with cephalosporin use is low, but not nil, and it may be more likely in patients with underlying disorders.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the National Cancer Institute, and by six Clinical and Translational Science Award grants. The investigators reported having no conflicts of interest.

Pelvic CT may not be needed to diagnose intra-abdominal injury in children

BY JENNIE SMITH

FROM SAEM 2015

But concerns about excess exposure to CT radiation, particularly to the gonads, led one group of researchers to question whether it’s necessary to scan the entire abdominopelvic region in all of these patients to identify IAI.

Dr Stacy Reynolds and her colleagues at the Carolinas Medical Center in Charlotte, North Carolina, hypothesized that CT limited to the radiographic abdomen – the region between the dome of the diaphragm to the top of the iliac crest – can capture the vast majority of IAIs in this population.

At the Society for Academic Emergency Medicine annual meeting, Dr Reynolds presented results from a retrospective cohort study enrolling 313 hemodynamically stable pediatric patients (median age 14 years, 64% male) presenting to 12 EDs after blunt trauma. Patients with known pelvic fractures or hip dislocation were excluded, as they would have had a clear indication for a full abdominopelvic CT.

All subjects underwent axial abdominopelvic CT imaging. Researchers created matched pairs of images comprising the original scans and those that had been altered with software that truncated the pelvic portion of the study to create CT abdomen-only studies. Study radiologists were blinded to the results of the original scans.

In all, 26 IAI’s were diagnosed in 24 patients: 8 hepatic injuries, 12 splenic injuries, 5 renal injuries, and 1 retroperitoneal hemorrhage. Abdominal CT alone was 85% sensitive (95% CI, 65%-96%) and 99% specific (95% CI, 97%-100%) in identifying IAIs. The four missed injuries were solid organ injuries within the radiographic abdomen. False positives occurred in two of the complete scans, both involving free fluid prompting suspicion of small bowel injury later ruled out by clinical observation.

Dr Reynolds said in an interview that the findings, while promising, were limited by the study’s small numbers, and its use of axial images alone, when sagittal images also would be required for the most accurate diagnoses. Also, physician suspicion of IAI prior to imaging was not captured because of the study’s retrospective design, she said. “The real key to whether or not this hypothesis is valuable is if physicians are able to target the right population of patients for application.”

Dr Reynolds cautioned that the findings would need to be validated in a larger trial before any changes could be made to clinical practice. “Some of the outcomes that we need to make sure whether we’re missing are still rare,” she said. “You couldn’t feel confident that this is the right way to go with a study this small, but it establishes that we can safely and ethically pursue a multicenter trial that would examine the issue with bigger numbers.”

Other groups of investigators, including members of the Pediatric Emergency Care Applied Research Network (PECARN), also have taken up the question of identifying children at low risk of IAI who may not need CT screening after blunt trauma. In 2013, PECARN published a prediction rule using only patient history and physical examination findings intended to obviate use of CT in the lowest-risk patients (Ann Emerg Med. 2013;62:107-116.e2).

Dr Reynolds said that while overuse of CT was a worrisome trend that could have long-term implications for patients, and that it was important to identify ways it might be limited, there is a reason it remains the go-to technology in the ED for detecting IAI. “It’s got very high sensitivity and specificity. If you’re a busy trauma surgeon who’s admitting 20 injured patients in a night, there’s no faster or more efficient way to determine whether the patient in front of you is injured.”

The ‘sad truth’ about suicide risk assessment scales

BY BRUCE JANCIN

EXPERT ANALYSIS FROM THE ANNUAL AAS CONFERENCE

ATLANTA – “Don’t – repeat, don’t – use risk assessment tools and scales in an effort to predict future suicide in patients who’ve committed intentional self-harm,” Dr Keith Hawton urged at the annual conference of the American Association of Suicidology.

He noted this isn’t simply a matter of his personal opinion; it’s also a strongly worded recommendation in the current UK NICE (National Institute for Health and Care Excellence) guidelines on the long-term management of patients who’ve committed self-harm. The various NICE guidelines, which address numerous areas of medical practice and are used to determine what’s reimbursable through the UK’s National Health Service, are famously evidence based and concerned with cost-effectiveness.

The NICE guidelines on management of self-harm further advise: “Do not use risk assessment tools and scales to determine who should and should not be offered treatment or who should be discharged from hospital.”

“Those are some fairly contentious statements about risk assessment scales. But those statements are based upon review of the evidence about the effectiveness of risk assessment scales,” according to Dr Hawton, professor of psychiatry and director of the Centre for Suicide Research at the University of Oxford (England).

Zhiltsov Alexandr/Shutterstock

“In our country, hospitals have become obsessed with risk assessment. And usually, it seems to be about protecting the organization rather than the patient, because so often the results aren’t linked to risk management, which is what we should be talking about,” he observed.

Dr Hawton and his colleagues provided some of the evidence that led to the NICE guideline committee’s thumbs-down on the use of suicide risk assessment scales in patients who’ve engaged in intentional self-harm. In a study provocatively titled “The sad truth about the SADPERSONS scale,” he and his coinvestigators essentially dismantled SADPERSONS, a widely used screening tool for suicide risk, concluding that it is without value.

The acronym stands for Sex (male), Age (<19 or >45), Depression, Previous attempts, Ethanol abuse, Rational thinking loss, Social supports lacking, Organized plan, No spouse, and Sickness. One point is given for each. Patients who score 7-10 are to be hospitalized, and those with a total of 5 or 6 points should be strongly considered for hospitalization.

Dr Hawton and coinvestigators tracked 126 consecutive patients who were evaluated for self-harm using the SADPERSONS scale in a general hospital emergency department and then followed them for 6 months. SADPERSONS performed miserably in predicting clinical management outcomes, such as admission to a psychiatric hospital or repetition of self-harm within 6 months. Indeed, the test failed to identify 4 of the 5 patients admitted to a psychiatric hospital, 65 of 70 who were referred from the ED to community psychiatric aftercare, and 28 of 31 who repeated self-harm within 6 months. Thus, its sensitivity as a predictor of repetition of self-harm was a lowly 6.6% (Emerg Med J. 2014;31:796-798).

And yet, a 32-hospital UK national study conducted by Dr Hawton and others found that SADPERSONS was the most widely used scale in EDs for risk assessment following self-harm (BMJ Open. 2014;4(5):e004732. doi:10.1136/bmjopen-2013-004732). “It’s a very crude tool,” Dr Hawton said. “How it found its way into common use in clinical practice is beyond me.”

[email protected] 

Diagnostic errors top malpractice claims against emergency physicians

BY ALICIA GALLEGOS
FRONTLINE MEDICAL NEWS

More than half of medical malpractice lawsuits against emergency physicians involve allegations of diagnostic errors, according to a study by national medical liability insurer The Doctors Company.

The study analyzed 332 emergency medicine claims in the insurer’s database that were closed from 2007 to 2013. The findings show the importance of strong communication in the emergency department (ED), and how communication breakdowns can be catalysts for legal claims, Darrell Ranum, vice president for patient safety and risk management for The Doctors Company, said.

Mr. Ranum pointed out one claim in which a patient’s vital signs had changed during the course of a visit. The changes were not communicated to the emergency physician, and he inappropriately discharged the patient. In another case, a patient’s history of overdoses was not conveyed during a patient hand-off, which resulted in an overdose that was not treated in a timely manner.

“Sometimes, we find that patients don’t always understand instructions,” Mr. Ranum said. “If patients don’t understand the communication from their providers or if a patient receives inadequate information, such as in situations where you have a language barrier, you can have problems there as well.”

Another key lesson from the study is the importance of a thorough differential diagnosis, Dr David B. Troxel, medical director for The Doctors Company said in an interview.

Of the 332 claims, 57% were diagnosis related; they included allegations of failure to establish a differential diagnosis, failure to order diagnostic tests, failure to address abnormal findings, and failure to consider available clinical information.

“Our hope is that as physicians review the findings of this study, they will scrutinize their own systems and processes and determine whether the weaknesses identified in the study exist in their organization,” Dr Troxel said.

Among the other claims, 13% related to improper management or treatment, 5% claimed improper performance of treatment, and 3% alleged failure to order medication.

Claims could have more than one contributing factor. Problems with patient assessments, such as failure to address abnormal findings, contributed to 52% of claims. Patient factors, such as physical characteristics and noncompliance, were the second-most-frequent contributor at 21%. Other factors were lack of communication among physicians (17%), poor communication between doctors and patients (14%), insufficient or lack of documentation (13%), and workflow/workload issues (12%). 

[email protected]

On Twitter @legal_med

ED-initiated buprenorphine ups treatment rates for opioid addiction

BY BIANCA NOGRADY
FROM JAMA

Initiating buprenorphine treatment during an emergency department visit can significantly increase the likelihood that opioid-dependent patients will seek addiction treatment, according to results of a randomized clinical trial published in April 28 in JAMA.

Researchers randomized 104 opioid-dependent patients who had presented to the ED to screening and treatment referral, screening and a brief intervention with referral to a community-based treatment service, or screening with a brief intervention and ED-initiated treatment with buprenorphine/naloxone and referral to primary care.

Significantly more patients in the buprenorphine group sought addiction treatment in the 30 days after randomization compared to the referral or intervention arms (78% vs. 37% vs. 45%, P < .001), and they showed significant reductions in the number of days of illicit opioid use per week.

“Expanded use of ED-initiated buprenorphine with community follow-up should help increase access to treatment options for this chronic and relapsing medical condition that has substantial morbidity and mortality and that affects health care use and costs,” wrote Dr Gail D’Onofrio of Yale School of Medicine, New Haven, Ct., and coauthors (JAMA 2015; 313:1636-1644 [doi:10.1001/jama.2015.3474]). 

More than 75% with sickle cell crises don’t get hydroxyurea

BY MARY ANN MOON
FROM JAMA

More than 75% of adults with sickle cell anemia who have frequent pain crises fail to receive hydroxyurea therapy as strongly recommended in National Heart, Lung, and Blood Institute clinical guidelines, according to a Research Letter to the Editor published online April 28 in JAMA.

Despite proven benefits in decreasing pain crises, hospitalizations, blood transfusions, and possibly mortality, hydroxyurea, a “safe and inexpensive drug,” is thought to be underused. To document the actual use of the drug when indicated, investigators analyzed information in a nationwide insurance claims database covering nearly 27 million patients per year. They focused on the records of 570 adults hospitalized or treated in an emergency department for a sickle cell pain crisis at least three times during a 1-year period, said Dr Nicolas Stettler of the Lewin Group, a health care consulting firm in Falls Church, Va., and his associates.

Only 15.1% of these patients received hydroxyurea within 3 months of their third crisis, only 18.2% received the agent within 6 months, and only 22.7% received it within 12 months. These figures likely represent a conservative estimate of the hydroxyurea treatment gap, since the study didn’t include the large uninsured and publicly insured populations who have more limited access to health care, Dr Stettler and his associates noted (JAMA 2015;313:1671-2).

Several barriers to this treatment have been identified in previous research, including fear of adverse events, lack of clinician training, and failure to use shared decision making. “To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit,” they added.

Recognizing human trafficking victims

BY ALICIA GALLEGOS
AT THE AMWA ANNUAL MEETING

CHICAGO – Emergency physicians encounter nearly 40% of human trafficking  victims who come in contact with health providers, according to Dr Holly G. Atkinson.

In a 2014 survey of domestic sex-trafficking victims, 88% said they encountered one or more health professions during the period in which they were being trafficked, yet none was identified as a victim by physicians during the visits. In another 2014 survey of survivors, 39% of victims reported having contact with emergency departments; 29%, with primary care physicians; 17%, with ob.gyns.; 17%, with dentists; and 3%, with pediatricians.

Key indicators for potential victimization include discrepancies between history and clinical presentation, multiple sexually transmitted diseases, and the accompaniment of a controlling third-party who is not a guardian, said Dr Atkinson, director of the human rights program at Arnhold Global Health Institute at the Icahn School of Medicine at Mount Sinai in New York City, said at the annual meeting of the American Medical Women’s Association.

In 2014, the National Human Trafficking Resource Center, operated by the antislavery organization Polaris, received 3,598 reports of sex-trafficking cases inside the United States. The National Center for Missing & Exploited Children estimates that between 100,000 and 300,000 U.S. children are at risk of being sexually trafficked each year.

Physical signs that could denote the possibility of patients being trafficked include visible tattoos with “daddy,” “property of,” or a trafficker’s street name. Perpetrators often brand their victims so that they are easily recognizable and can be returned if they escape, Dr Atkinson explained.

Dehydration, malnutrition, multiple sexually transmitted infections, and multiple pregnancies or abortions could also be clues. The inability to provide an address, confusion about their current location, an appearance younger than the stated age, avoidance of eye contact, and answers that sound scripted are potential signs of human trafficking, as is the presence of a controlling third party who does not let the patient answer questions or who interrupts or corrects the patient.

The Via Christi Health system in Wichita, Kan., recently published guidance for clinicians on how to proceed if they suspect a patient is a victim of human trafficking. Steps include following child abuse or domestic violence protocols; separating the patient from the controlling third party; providing the patient a comfortable, safe area; and ensuring a patient interview is performed by a trauma-informed social worker or nurse.

Some questions physicians may want to ask patients include: Have you ever exchanged sex for money, food, or shelter? Have you been forced to have sex against your will? Have you been asked to have sex with multiple partners? If the patient answers yes, physicians should follow child abuse protocols and mandatory reporting requirements. If the patient is aged 18 or older, doctors should obtain the patient’s permission to call law enforcement or assist the patient in calling 911.

AMWA recently launched Physicians Against the Trafficking of Humans (PATH). The PATH website includes resources for physicians and an online video about trafficking that doctors can share with their practices and colleagues. 

[email protected]

On Twitter @legal_med

Indiana HIV outbreak prompts national advisory

BY SHARON WORCESTER
FRONTLINE MEDICAL NEWS

As health officials continue to battle an intravenous drug use–related HIV outbreak in a rural county in Indiana, the Centers for Disease Control and Prevention has issued an official health advisory stressing the need for vigilance at the state and local levels with respect to detecting and controlling similar outbreaks across the United States.

The Indiana outbreak began in November, with 11 new HIV infections diagnosed by January in Scott County, where fewer than 5 infections per year had been identified previously; since January, an unprecedented 135 infections have been confirmed, and 6 others are under investigation, according to Dr Jerome M. Adams, Indiana State Health Commissioner.

“To put this in further perspective, from 2009 through 2013, the county only reported three new cases of HIV,” Dr Adams said in a joint Indiana State Department of Health/CDC teleconference.

The affected community includes only 4,200 people, and 84% of those diagnosed with HIV also tested positive for hepatitis C virus (HCV) infection, Dr Joan Duwve, chief medical consultant, Indiana State Department of Health, said during the teleconference.

According to the CDC advisory, 96% of 108 infected individuals who were interviewed reported injecting dissolved prescription-type oxymorphone, as well as sharing syringes.

“The United States is facing an epidemic of prescription opioid abuse that must be addressed. Opioid poisoning deaths have nearly quadrupled from 1999 through 2011. This epidemic of opioid abuse has already contributed to a severe and growing epidemic of viral hepatitis among people who inject drugs,” said Dr Jonathan Mermin, director of the National Center for HIV/AIDS Viral Hepatitis, STD, and TB Prevention, who also participated in the teleconference.

New CDC data on HCV show a 150% increase in reports of acute HCV infections nationwide between 2010 to 2013.

“The majority of these infections  are believed to be attributable to injection drug use, so we must act now to reverse this trend and to prevent this from undoing progress in HIV prevention to date,” he said.

Among the recommendations were routine opt-out of HIV testing as well as HCV testing per current recommendations. Further, health care professionals should report suspected clusters to their local or state health department, ensure that HCV-infected patients are also tested for HIV and vice versa, and ensure that those receiving treatment for either HIV or HCV are adhering to prescribed therapy and are engaged in ongoing care.

Syringe-sharing and sexual partners of those diagnosed with HIV or HCV should be encouraged to undergo testing, and all persons with substance abuse problems should be referred for medication-assisted treatment and counseling. In Indiana, where a public health emergency was declared on March 26 and has been extended until May 24, care includes HIV and HCV treatment, as well as substance abuse counseling and treatment, according to a “Notes From the Field Report” in the Morbidity and Mortality Weekly Report (MMWR 2015 April 24;64:1-2).

[email protected]

Most accidental genital trauma cases manageable in ED

BY SHARON WORCESTER

AT THE NASPAG ANNUAL MEETING

ORLANDO – Most cases of accidental genital trauma in girls are caused by straddle injuries and are isolated to the labia, and most can be managed expectantly or treated in the emergency department, according to findings from a retrospective cohort study.

Penetrating injuries, however, should be considered an indication for management in the operating room, Dr Tazim Dowlut-McElroy reported at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

A review of 359 cases showed that the vast majority – 82% – were minor and managed expectantly.

“Only 18% required surgical management. Of those, 37% required general anesthesia in the OR, but 63% were adequately evaluated and treated in the ED,” said Dr Dowlut-McElroy of Children’s Mercy Hospitals and Clinics, Kansas City.

About 64% of the patients presented during the day, and 36% presented at night. The most common presenting complaint was bleeding and pain (89% of cases), followed by voiding issues in 8% of cases. No presenting complaint was recorded in the remaining patient charts.

The most common mechanism of injury was straddle injury (73% of cases), followed by non-straddle blunt trauma in 15% of cases, and penetrating injury in the remaining cases, Dr Dowlut-McElroy said.

Injuries included lacerations in 86% of cases, abrasions or contusions in 7%, and hematomas in 3%.

Pediatric genital injuries comprised 0.2%-8% of reported childhood trauma, and despite public health efforts to reduce injuries, the number of such pediatric injuries continues to rise, Dr Dowlut-McElroy said.

Patients included in the current review were identified by a medical database query from January 2000 to July 2014. They were aged 0-18 years and had been treated in the ED for genital trauma; those with obstetrical injuries were excluded. 

[email protected]

EDs pump up pediatric preparedness

BY MARY ANN MOON

FROM JAMA PEDIATRICS

Pediatric readiness has improved in emergency departments across the country, as measured by EDs’ compliance with 2009 guidelines for emergency care in children, according to a report published online April 13 in JAMA Pediatrics.

In what they described as “the most comprehensive evaluation of pediatric readiness of our nation’s EDs to date,” investigators performed a web-based assessment of 4,137 hospitals’ self-reported compliance with guidelines addressing child-specific emergency care. The overall median weighted pediatric readiness score (WPRS) was 68.9, a solid improvement over the previously reported median WPRS of 55, said Dr Marianne Gausche-Hill of Harbor-UCLA Medical Center, Torrance, Calif., and her associates. 

The single most important factor found to enhance pediatric readiness was to designate two people, one of whom is a physician or nurse, as the hospital’s pediatric emergency care coordinator, as recommended by the Institute of Medicine, the researchers wrote. Nearly half (47.5%) of EDs now have a physician coordinator, and 59.3% now have a nurse coordinator, compared with 18% and 12%, respectively, in a previous report. The presence of coordinators quadrupled the chances that a hospital would put important quality-improvement plans in place to address children’s care needs, the investigators said (JAMA Pediatr. 2015 April 13 [doi:10.1001/jamapediatrics.2015.138]).

Other findings included the following:

• Most physicians providing emergency care for children were specifically trained in emergency medicine (88.6%) or pediatric emergency medicine (55.4%) at high-volume hospitals; low-volume hospitals were more likely to have family-medicine-trained physicians doing so (78.9%).
• Mandatory competency evaluations for providing pediatric emergency care were relatively common for nurses (66.6%) but less so for physicians (38.7%) and midlevel staff (18.1%).
• 99.5% of EDs said all staff are trained on the location of pediatric equipment in the ED, including tools to ensure correct sizing of resuscitation equipment and appropriate dosing of medications.
• 83.1% of EDs said they verified the proper location and function of pediatric equipment daily.
• EDs routinely stocked 91% of recommended pediatric equipment. Equipment that was missing in more than 15% of EDs included laryngeal mask airways, umbilical vein catheters, central venous catheters, tracheostomy tubes, size 00 laryngoscope blades, continuous end-tidal carbon dioxide monitoring equipment, pediatric Magill forceps, and infant and child nasopharyngeal airways.
• Only 46.8% of EDs had disaster plans that specifically addressed children, as recommended. Even among high-volume hospitals, which were the most compliant with guidelines, only 67.4% had such disaster plans.
• Approximately one-third of EDs said their providers failed to weigh children and record the weight in kilograms only, as recommended. This safety measure is crucial to preventing drug-dosing errors.
• The most frequently cited barriers to complying with guidelines were the cost of child-specific training (reported by 54.4% of EDs) and a lack of educational resources (reported by 49.0%). Few EDs reported that a lack of interest was a barrier to implementing the guidelines. 

Simplified PESI identified low-risk pulmonary embolism

BY AMY KARON

FROM ACADEMIC EMERGENCY MEDICINE

A simplified version of the Pulmonary Embolism Severity Index identified patients with acute pulmonary embolism who were at low risk of adverse events and might be suitable for outpatient care.

“Although guidelines, such as those from the American College of Chest Physicians, recommend outpatient treatment for selected PE patients at low risk of recurrence, existing evidence for the outpatient management of patients with PE is derived from small cohorts of patients from outside the United States,” said Dr Gregory J. Fermann of the University of Cincinnati department of emergency medicine and his associates.  “Risk stratification of PE patients may allow a cohort of low-risk patients to be treated in a clinical decision unit or by a closely monitored outpatient strategy. Such an approach might relieve some of the burden placed on the emergency department,” they wrote (Acad. Emerg. Med. 2015;22:299-307).

The simplified PESI includes 6 of the 11 variables measured in PESI, which has been shown to identify patients at increased risk of death and adverse outcome events after acute PE. The six features of the simplified PESI are age greater than 80 years, history of cancer, history of chronic cardiopulmonary disease, heart rate of at least 110 beats per minutes, systolic blood pressure less than 100 mm Hg, and oxygen saturation less than 90%. Each factor is assigned a score of 1.

They carried out a post hoc analysis of simplified PESI scores and outcomes among 4,831 acute PE patients from the EINSTEIN-PE study of rivaroxaban  and an enoxaparin–vitamin K antagonist combination (N. Engl. J. Med. 2012;366:1287-97).

Roughly half (53.6%) of the patients had a score of 0, one-third (36.7%) had a score of 1, and 9.7% had a score of 2 or 3, the researchers reported. Higher simplified PESI scores were associated with increased risk of almost all adverse outcomes measured, including recurrent VTE, fatal PE, all-cause mortality, and major bleeding. Patients with scores of 0 or 1 had low rates of major adverse events during the first 30 days of treatment, regardless of which protocol they received. Scores of 2 or 3 were associated with greater risk of recurrent VTE, fatal PE, all-cause mortality, and major bleeding in both treatment groups.

Diagnostic errors top malpractice claims against emergency physicians

BY ALICIA GALLEGOS
FRONTLINE MEDICAL NEWS

More than half of medical malpractice lawsuits against emergency physicians involve allegations of diagnostic errors, according to a study by national medical liability insurer The Doctors Company.

The study analyzed 332 emergency medicine claims in the insurer’s database that were closed from 2007 to 2013. The findings show the importance of strong communication in the emergency department (ED), and how communication breakdowns can be catalysts for legal claims, Darrell Ranum, vice president for patient safety and risk management for The Doctors Company, said.

Mr. Ranum pointed out one claim in which a patient’s vital signs had changed during the course of a visit. The changes were not communicated to the emergency physician, and he inappropriately discharged the patient. In another case, a patient’s history of overdoses was not conveyed during a patient hand-off, which resulted in an overdose that was not treated in a timely manner.

“Sometimes, we find that patients don’t always understand instructions,” Mr. Ranum said. “If patients don’t understand the communication from their providers or if a patient receives inadequate information, such as in situations where you have a language barrier, you can have problems there as well.”

Another key lesson from the study is the importance of a thorough differential diagnosis, Dr David B. Troxel, medical director for The Doctors Company said in an interview.

Of the 332 claims, 57% were diagnosis related; they included allegations of failure to establish a differential diagnosis, failure to order diagnostic tests, failure to address abnormal findings, and failure to consider available clinical information.

“Our hope is that as physicians review the findings of this study, they will scrutinize their own systems and processes and determine whether the weaknesses identified in the study exist in their organization,” Dr Troxel said.

Among the other claims, 13% related to improper management or treatment, 5% claimed improper performance of treatment, and 3% alleged failure to order medication.

Claims could have more than one contributing factor. Problems with patient assessments, such as failure to address abnormal findings, contributed to 52% of claims. Patient factors, such as physical characteristics and noncompliance, were the second-most-frequent contributor at 21%. Other factors were lack of communication among physicians (17%), poor communication between doctors and patients (14%), insufficient or lack of documentation (13%), and workflow/workload issues (12%). 

[email protected]

On Twitter @legal_med

ED-initiated buprenorphine ups treatment rates for opioid addiction

BY BIANCA NOGRADY
FROM JAMA

Initiating buprenorphine treatment during an emergency department visit can significantly increase the likelihood that opioid-dependent patients will seek addiction treatment, according to results of a randomized clinical trial published in April 28 in JAMA.

Researchers randomized 104 opioid-dependent patients who had presented to the ED to screening and treatment referral, screening and a brief intervention with referral to a community-based treatment service, or screening with a brief intervention and ED-initiated treatment with buprenorphine/naloxone and referral to primary care.

Significantly more patients in the buprenorphine group sought addiction treatment in the 30 days after randomization compared to the referral or intervention arms (78% vs. 37% vs. 45%, P < .001), and they showed significant reductions in the number of days of illicit opioid use per week.

“Expanded use of ED-initiated buprenorphine with community follow-up should help increase access to treatment options for this chronic and relapsing medical condition that has substantial morbidity and mortality and that affects health care use and costs,” wrote Dr Gail D’Onofrio of Yale School of Medicine, New Haven, Ct., and coauthors (JAMA 2015; 313:1636-1644 [doi:10.1001/jama.2015.3474]). 

More than 75% with sickle cell crises don’t get hydroxyurea

BY MARY ANN MOON
FROM JAMA

More than 75% of adults with sickle cell anemia who have frequent pain crises fail to receive hydroxyurea therapy as strongly recommended in National Heart, Lung, and Blood Institute clinical guidelines, according to a Research Letter to the Editor published online April 28 in JAMA.

Despite proven benefits in decreasing pain crises, hospitalizations, blood transfusions, and possibly mortality, hydroxyurea, a “safe and inexpensive drug,” is thought to be underused. To document the actual use of the drug when indicated, investigators analyzed information in a nationwide insurance claims database covering nearly 27 million patients per year. They focused on the records of 570 adults hospitalized or treated in an emergency department for a sickle cell pain crisis at least three times during a 1-year period, said Dr Nicolas Stettler of the Lewin Group, a health care consulting firm in Falls Church, Va., and his associates.

Only 15.1% of these patients received hydroxyurea within 3 months of their third crisis, only 18.2% received the agent within 6 months, and only 22.7% received it within 12 months. These figures likely represent a conservative estimate of the hydroxyurea treatment gap, since the study didn’t include the large uninsured and publicly insured populations who have more limited access to health care, Dr Stettler and his associates noted (JAMA 2015;313:1671-2).

Several barriers to this treatment have been identified in previous research, including fear of adverse events, lack of clinician training, and failure to use shared decision making. “To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit,” they added.

Recognizing human trafficking victims

BY ALICIA GALLEGOS
AT THE AMWA ANNUAL MEETING

CHICAGO – Emergency physicians encounter nearly 40% of human trafficking  victims who come in contact with health providers, according to Dr Holly G. Atkinson.

In a 2014 survey of domestic sex-trafficking victims, 88% said they encountered one or more health professions during the period in which they were being trafficked, yet none was identified as a victim by physicians during the visits. In another 2014 survey of survivors, 39% of victims reported having contact with emergency departments; 29%, with primary care physicians; 17%, with ob.gyns.; 17%, with dentists; and 3%, with pediatricians.

Key indicators for potential victimization include discrepancies between history and clinical presentation, multiple sexually transmitted diseases, and the accompaniment of a controlling third-party who is not a guardian, said Dr Atkinson, director of the human rights program at Arnhold Global Health Institute at the Icahn School of Medicine at Mount Sinai in New York City, said at the annual meeting of the American Medical Women’s Association.

In 2014, the National Human Trafficking Resource Center, operated by the antislavery organization Polaris, received 3,598 reports of sex-trafficking cases inside the United States. The National Center for Missing & Exploited Children estimates that between 100,000 and 300,000 U.S. children are at risk of being sexually trafficked each year.

Physical signs that could denote the possibility of patients being trafficked include visible tattoos with “daddy,” “property of,” or a trafficker’s street name. Perpetrators often brand their victims so that they are easily recognizable and can be returned if they escape, Dr Atkinson explained.

Dehydration, malnutrition, multiple sexually transmitted infections, and multiple pregnancies or abortions could also be clues. The inability to provide an address, confusion about their current location, an appearance younger than the stated age, avoidance of eye contact, and answers that sound scripted are potential signs of human trafficking, as is the presence of a controlling third party who does not let the patient answer questions or who interrupts or corrects the patient.

The Via Christi Health system in Wichita, Kan., recently published guidance for clinicians on how to proceed if they suspect a patient is a victim of human trafficking. Steps include following child abuse or domestic violence protocols; separating the patient from the controlling third party; providing the patient a comfortable, safe area; and ensuring a patient interview is performed by a trauma-informed social worker or nurse.

Some questions physicians may want to ask patients include: Have you ever exchanged sex for money, food, or shelter? Have you been forced to have sex against your will? Have you been asked to have sex with multiple partners? If the patient answers yes, physicians should follow child abuse protocols and mandatory reporting requirements. If the patient is aged 18 or older, doctors should obtain the patient’s permission to call law enforcement or assist the patient in calling 911.

AMWA recently launched Physicians Against the Trafficking of Humans (PATH). The PATH website includes resources for physicians and an online video about trafficking that doctors can share with their practices and colleagues. 

[email protected]

On Twitter @legal_med

Indiana HIV outbreak prompts national advisory

BY SHARON WORCESTER
FRONTLINE MEDICAL NEWS

As health officials continue to battle an intravenous drug use–related HIV outbreak in a rural county in Indiana, the Centers for Disease Control and Prevention has issued an official health advisory stressing the need for vigilance at the state and local levels with respect to detecting and controlling similar outbreaks across the United States.

The Indiana outbreak began in November, with 11 new HIV infections diagnosed by January in Scott County, where fewer than 5 infections per year had been identified previously; since January, an unprecedented 135 infections have been confirmed, and 6 others are under investigation, according to Dr Jerome M. Adams, Indiana State Health Commissioner.

“To put this in further perspective, from 2009 through 2013, the county only reported three new cases of HIV,” Dr Adams said in a joint Indiana State Department of Health/CDC teleconference.

The affected community includes only 4,200 people, and 84% of those diagnosed with HIV also tested positive for hepatitis C virus (HCV) infection, Dr Joan Duwve, chief medical consultant, Indiana State Department of Health, said during the teleconference.

According to the CDC advisory, 96% of 108 infected individuals who were interviewed reported injecting dissolved prescription-type oxymorphone, as well as sharing syringes.

“The United States is facing an epidemic of prescription opioid abuse that must be addressed. Opioid poisoning deaths have nearly quadrupled from 1999 through 2011. This epidemic of opioid abuse has already contributed to a severe and growing epidemic of viral hepatitis among people who inject drugs,” said Dr Jonathan Mermin, director of the National Center for HIV/AIDS Viral Hepatitis, STD, and TB Prevention, who also participated in the teleconference.

New CDC data on HCV show a 150% increase in reports of acute HCV infections nationwide between 2010 to 2013.

“The majority of these infections  are believed to be attributable to injection drug use, so we must act now to reverse this trend and to prevent this from undoing progress in HIV prevention to date,” he said.

Among the recommendations were routine opt-out of HIV testing as well as HCV testing per current recommendations. Further, health care professionals should report suspected clusters to their local or state health department, ensure that HCV-infected patients are also tested for HIV and vice versa, and ensure that those receiving treatment for either HIV or HCV are adhering to prescribed therapy and are engaged in ongoing care.

Syringe-sharing and sexual partners of those diagnosed with HIV or HCV should be encouraged to undergo testing, and all persons with substance abuse problems should be referred for medication-assisted treatment and counseling. In Indiana, where a public health emergency was declared on March 26 and has been extended until May 24, care includes HIV and HCV treatment, as well as substance abuse counseling and treatment, according to a “Notes From the Field Report” in the Morbidity and Mortality Weekly Report (MMWR 2015 April 24;64:1-2).

[email protected]

Most accidental genital trauma cases manageable in ED

BY SHARON WORCESTER

AT THE NASPAG ANNUAL MEETING

ORLANDO – Most cases of accidental genital trauma in girls are caused by straddle injuries and are isolated to the labia, and most can be managed expectantly or treated in the emergency department, according to findings from a retrospective cohort study.

Penetrating injuries, however, should be considered an indication for management in the operating room, Dr Tazim Dowlut-McElroy reported at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

A review of 359 cases showed that the vast majority – 82% – were minor and managed expectantly.

“Only 18% required surgical management. Of those, 37% required general anesthesia in the OR, but 63% were adequately evaluated and treated in the ED,” said Dr Dowlut-McElroy of Children’s Mercy Hospitals and Clinics, Kansas City.

About 64% of the patients presented during the day, and 36% presented at night. The most common presenting complaint was bleeding and pain (89% of cases), followed by voiding issues in 8% of cases. No presenting complaint was recorded in the remaining patient charts.

The most common mechanism of injury was straddle injury (73% of cases), followed by non-straddle blunt trauma in 15% of cases, and penetrating injury in the remaining cases, Dr Dowlut-McElroy said.

Injuries included lacerations in 86% of cases, abrasions or contusions in 7%, and hematomas in 3%.

Pediatric genital injuries comprised 0.2%-8% of reported childhood trauma, and despite public health efforts to reduce injuries, the number of such pediatric injuries continues to rise, Dr Dowlut-McElroy said.

Patients included in the current review were identified by a medical database query from January 2000 to July 2014. They were aged 0-18 years and had been treated in the ED for genital trauma; those with obstetrical injuries were excluded. 

[email protected]

EDs pump up pediatric preparedness

BY MARY ANN MOON

FROM JAMA PEDIATRICS

Pediatric readiness has improved in emergency departments across the country, as measured by EDs’ compliance with 2009 guidelines for emergency care in children, according to a report published online April 13 in JAMA Pediatrics.

In what they described as “the most comprehensive evaluation of pediatric readiness of our nation’s EDs to date,” investigators performed a web-based assessment of 4,137 hospitals’ self-reported compliance with guidelines addressing child-specific emergency care. The overall median weighted pediatric readiness score (WPRS) was 68.9, a solid improvement over the previously reported median WPRS of 55, said Dr Marianne Gausche-Hill of Harbor-UCLA Medical Center, Torrance, Calif., and her associates. 

The single most important factor found to enhance pediatric readiness was to designate two people, one of whom is a physician or nurse, as the hospital’s pediatric emergency care coordinator, as recommended by the Institute of Medicine, the researchers wrote. Nearly half (47.5%) of EDs now have a physician coordinator, and 59.3% now have a nurse coordinator, compared with 18% and 12%, respectively, in a previous report. The presence of coordinators quadrupled the chances that a hospital would put important quality-improvement plans in place to address children’s care needs, the investigators said (JAMA Pediatr. 2015 April 13 [doi:10.1001/jamapediatrics.2015.138]).

Other findings included the following:

• Most physicians providing emergency care for children were specifically trained in emergency medicine (88.6%) or pediatric emergency medicine (55.4%) at high-volume hospitals; low-volume hospitals were more likely to have family-medicine-trained physicians doing so (78.9%).
• Mandatory competency evaluations for providing pediatric emergency care were relatively common for nurses (66.6%) but less so for physicians (38.7%) and midlevel staff (18.1%).
• 99.5% of EDs said all staff are trained on the location of pediatric equipment in the ED, including tools to ensure correct sizing of resuscitation equipment and appropriate dosing of medications.
• 83.1% of EDs said they verified the proper location and function of pediatric equipment daily.
• EDs routinely stocked 91% of recommended pediatric equipment. Equipment that was missing in more than 15% of EDs included laryngeal mask airways, umbilical vein catheters, central venous catheters, tracheostomy tubes, size 00 laryngoscope blades, continuous end-tidal carbon dioxide monitoring equipment, pediatric Magill forceps, and infant and child nasopharyngeal airways.
• Only 46.8% of EDs had disaster plans that specifically addressed children, as recommended. Even among high-volume hospitals, which were the most compliant with guidelines, only 67.4% had such disaster plans.
• Approximately one-third of EDs said their providers failed to weigh children and record the weight in kilograms only, as recommended. This safety measure is crucial to preventing drug-dosing errors.
• The most frequently cited barriers to complying with guidelines were the cost of child-specific training (reported by 54.4% of EDs) and a lack of educational resources (reported by 49.0%). Few EDs reported that a lack of interest was a barrier to implementing the guidelines. 

Simplified PESI identified low-risk pulmonary embolism

BY AMY KARON

FROM ACADEMIC EMERGENCY MEDICINE

A simplified version of the Pulmonary Embolism Severity Index identified patients with acute pulmonary embolism who were at low risk of adverse events and might be suitable for outpatient care.

“Although guidelines, such as those from the American College of Chest Physicians, recommend outpatient treatment for selected PE patients at low risk of recurrence, existing evidence for the outpatient management of patients with PE is derived from small cohorts of patients from outside the United States,” said Dr Gregory J. Fermann of the University of Cincinnati department of emergency medicine and his associates.  “Risk stratification of PE patients may allow a cohort of low-risk patients to be treated in a clinical decision unit or by a closely monitored outpatient strategy. Such an approach might relieve some of the burden placed on the emergency department,” they wrote (Acad. Emerg. Med. 2015;22:299-307).

The simplified PESI includes 6 of the 11 variables measured in PESI, which has been shown to identify patients at increased risk of death and adverse outcome events after acute PE. The six features of the simplified PESI are age greater than 80 years, history of cancer, history of chronic cardiopulmonary disease, heart rate of at least 110 beats per minutes, systolic blood pressure less than 100 mm Hg, and oxygen saturation less than 90%. Each factor is assigned a score of 1.

They carried out a post hoc analysis of simplified PESI scores and outcomes among 4,831 acute PE patients from the EINSTEIN-PE study of rivaroxaban  and an enoxaparin–vitamin K antagonist combination (N. Engl. J. Med. 2012;366:1287-97).

Roughly half (53.6%) of the patients had a score of 0, one-third (36.7%) had a score of 1, and 9.7% had a score of 2 or 3, the researchers reported. Higher simplified PESI scores were associated with increased risk of almost all adverse outcomes measured, including recurrent VTE, fatal PE, all-cause mortality, and major bleeding. Patients with scores of 0 or 1 had low rates of major adverse events during the first 30 days of treatment, regardless of which protocol they received. Scores of 2 or 3 were associated with greater risk of recurrent VTE, fatal PE, all-cause mortality, and major bleeding in both treatment groups.

Diagnostic errors top malpractice claims against emergency physicians

BY ALICIA GALLEGOS
FRONTLINE MEDICAL NEWS

More than half of medical malpractice lawsuits against emergency physicians involve allegations of diagnostic errors, according to a study by national medical liability insurer The Doctors Company.

The study analyzed 332 emergency medicine claims in the insurer’s database that were closed from 2007 to 2013. The findings show the importance of strong communication in the emergency department (ED), and how communication breakdowns can be catalysts for legal claims, Darrell Ranum, vice president for patient safety and risk management for The Doctors Company, said.

Mr. Ranum pointed out one claim in which a patient’s vital signs had changed during the course of a visit. The changes were not communicated to the emergency physician, and he inappropriately discharged the patient. In another case, a patient’s history of overdoses was not conveyed during a patient hand-off, which resulted in an overdose that was not treated in a timely manner.

“Sometimes, we find that patients don’t always understand instructions,” Mr. Ranum said. “If patients don’t understand the communication from their providers or if a patient receives inadequate information, such as in situations where you have a language barrier, you can have problems there as well.”

Another key lesson from the study is the importance of a thorough differential diagnosis, Dr David B. Troxel, medical director for The Doctors Company said in an interview.

Of the 332 claims, 57% were diagnosis related; they included allegations of failure to establish a differential diagnosis, failure to order diagnostic tests, failure to address abnormal findings, and failure to consider available clinical information.

“Our hope is that as physicians review the findings of this study, they will scrutinize their own systems and processes and determine whether the weaknesses identified in the study exist in their organization,” Dr Troxel said.

Among the other claims, 13% related to improper management or treatment, 5% claimed improper performance of treatment, and 3% alleged failure to order medication.

Claims could have more than one contributing factor. Problems with patient assessments, such as failure to address abnormal findings, contributed to 52% of claims. Patient factors, such as physical characteristics and noncompliance, were the second-most-frequent contributor at 21%. Other factors were lack of communication among physicians (17%), poor communication between doctors and patients (14%), insufficient or lack of documentation (13%), and workflow/workload issues (12%). 

[email protected]

On Twitter @legal_med

ED-initiated buprenorphine ups treatment rates for opioid addiction

BY BIANCA NOGRADY
FROM JAMA

Initiating buprenorphine treatment during an emergency department visit can significantly increase the likelihood that opioid-dependent patients will seek addiction treatment, according to results of a randomized clinical trial published in April 28 in JAMA.

Researchers randomized 104 opioid-dependent patients who had presented to the ED to screening and treatment referral, screening and a brief intervention with referral to a community-based treatment service, or screening with a brief intervention and ED-initiated treatment with buprenorphine/naloxone and referral to primary care.

Significantly more patients in the buprenorphine group sought addiction treatment in the 30 days after randomization compared to the referral or intervention arms (78% vs. 37% vs. 45%, P < .001), and they showed significant reductions in the number of days of illicit opioid use per week.

“Expanded use of ED-initiated buprenorphine with community follow-up should help increase access to treatment options for this chronic and relapsing medical condition that has substantial morbidity and mortality and that affects health care use and costs,” wrote Dr Gail D’Onofrio of Yale School of Medicine, New Haven, Ct., and coauthors (JAMA 2015; 313:1636-1644 [doi:10.1001/jama.2015.3474]). 

More than 75% with sickle cell crises don’t get hydroxyurea

BY MARY ANN MOON
FROM JAMA

More than 75% of adults with sickle cell anemia who have frequent pain crises fail to receive hydroxyurea therapy as strongly recommended in National Heart, Lung, and Blood Institute clinical guidelines, according to a Research Letter to the Editor published online April 28 in JAMA.

Despite proven benefits in decreasing pain crises, hospitalizations, blood transfusions, and possibly mortality, hydroxyurea, a “safe and inexpensive drug,” is thought to be underused. To document the actual use of the drug when indicated, investigators analyzed information in a nationwide insurance claims database covering nearly 27 million patients per year. They focused on the records of 570 adults hospitalized or treated in an emergency department for a sickle cell pain crisis at least three times during a 1-year period, said Dr Nicolas Stettler of the Lewin Group, a health care consulting firm in Falls Church, Va., and his associates.

Only 15.1% of these patients received hydroxyurea within 3 months of their third crisis, only 18.2% received the agent within 6 months, and only 22.7% received it within 12 months. These figures likely represent a conservative estimate of the hydroxyurea treatment gap, since the study didn’t include the large uninsured and publicly insured populations who have more limited access to health care, Dr Stettler and his associates noted (JAMA 2015;313:1671-2).

Several barriers to this treatment have been identified in previous research, including fear of adverse events, lack of clinician training, and failure to use shared decision making. “To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit,” they added.

Recognizing human trafficking victims

BY ALICIA GALLEGOS
AT THE AMWA ANNUAL MEETING

CHICAGO – Emergency physicians encounter nearly 40% of human trafficking  victims who come in contact with health providers, according to Dr Holly G. Atkinson.

In a 2014 survey of domestic sex-trafficking victims, 88% said they encountered one or more health professions during the period in which they were being trafficked, yet none was identified as a victim by physicians during the visits. In another 2014 survey of survivors, 39% of victims reported having contact with emergency departments; 29%, with primary care physicians; 17%, with ob.gyns.; 17%, with dentists; and 3%, with pediatricians.

Key indicators for potential victimization include discrepancies between history and clinical presentation, multiple sexually transmitted diseases, and the accompaniment of a controlling third-party who is not a guardian, said Dr Atkinson, director of the human rights program at Arnhold Global Health Institute at the Icahn School of Medicine at Mount Sinai in New York City, said at the annual meeting of the American Medical Women’s Association.

In 2014, the National Human Trafficking Resource Center, operated by the antislavery organization Polaris, received 3,598 reports of sex-trafficking cases inside the United States. The National Center for Missing & Exploited Children estimates that between 100,000 and 300,000 U.S. children are at risk of being sexually trafficked each year.

Physical signs that could denote the possibility of patients being trafficked include visible tattoos with “daddy,” “property of,” or a trafficker’s street name. Perpetrators often brand their victims so that they are easily recognizable and can be returned if they escape, Dr Atkinson explained.

Dehydration, malnutrition, multiple sexually transmitted infections, and multiple pregnancies or abortions could also be clues. The inability to provide an address, confusion about their current location, an appearance younger than the stated age, avoidance of eye contact, and answers that sound scripted are potential signs of human trafficking, as is the presence of a controlling third party who does not let the patient answer questions or who interrupts or corrects the patient.

The Via Christi Health system in Wichita, Kan., recently published guidance for clinicians on how to proceed if they suspect a patient is a victim of human trafficking. Steps include following child abuse or domestic violence protocols; separating the patient from the controlling third party; providing the patient a comfortable, safe area; and ensuring a patient interview is performed by a trauma-informed social worker or nurse.

Some questions physicians may want to ask patients include: Have you ever exchanged sex for money, food, or shelter? Have you been forced to have sex against your will? Have you been asked to have sex with multiple partners? If the patient answers yes, physicians should follow child abuse protocols and mandatory reporting requirements. If the patient is aged 18 or older, doctors should obtain the patient’s permission to call law enforcement or assist the patient in calling 911.

AMWA recently launched Physicians Against the Trafficking of Humans (PATH). The PATH website includes resources for physicians and an online video about trafficking that doctors can share with their practices and colleagues. 

[email protected]

On Twitter @legal_med

Indiana HIV outbreak prompts national advisory

BY SHARON WORCESTER
FRONTLINE MEDICAL NEWS

As health officials continue to battle an intravenous drug use–related HIV outbreak in a rural county in Indiana, the Centers for Disease Control and Prevention has issued an official health advisory stressing the need for vigilance at the state and local levels with respect to detecting and controlling similar outbreaks across the United States.

The Indiana outbreak began in November, with 11 new HIV infections diagnosed by January in Scott County, where fewer than 5 infections per year had been identified previously; since January, an unprecedented 135 infections have been confirmed, and 6 others are under investigation, according to Dr Jerome M. Adams, Indiana State Health Commissioner.

“To put this in further perspective, from 2009 through 2013, the county only reported three new cases of HIV,” Dr Adams said in a joint Indiana State Department of Health/CDC teleconference.

The affected community includes only 4,200 people, and 84% of those diagnosed with HIV also tested positive for hepatitis C virus (HCV) infection, Dr Joan Duwve, chief medical consultant, Indiana State Department of Health, said during the teleconference.

According to the CDC advisory, 96% of 108 infected individuals who were interviewed reported injecting dissolved prescription-type oxymorphone, as well as sharing syringes.

“The United States is facing an epidemic of prescription opioid abuse that must be addressed. Opioid poisoning deaths have nearly quadrupled from 1999 through 2011. This epidemic of opioid abuse has already contributed to a severe and growing epidemic of viral hepatitis among people who inject drugs,” said Dr Jonathan Mermin, director of the National Center for HIV/AIDS Viral Hepatitis, STD, and TB Prevention, who also participated in the teleconference.

New CDC data on HCV show a 150% increase in reports of acute HCV infections nationwide between 2010 to 2013.

“The majority of these infections  are believed to be attributable to injection drug use, so we must act now to reverse this trend and to prevent this from undoing progress in HIV prevention to date,” he said.

Among the recommendations were routine opt-out of HIV testing as well as HCV testing per current recommendations. Further, health care professionals should report suspected clusters to their local or state health department, ensure that HCV-infected patients are also tested for HIV and vice versa, and ensure that those receiving treatment for either HIV or HCV are adhering to prescribed therapy and are engaged in ongoing care.

Syringe-sharing and sexual partners of those diagnosed with HIV or HCV should be encouraged to undergo testing, and all persons with substance abuse problems should be referred for medication-assisted treatment and counseling. In Indiana, where a public health emergency was declared on March 26 and has been extended until May 24, care includes HIV and HCV treatment, as well as substance abuse counseling and treatment, according to a “Notes From the Field Report” in the Morbidity and Mortality Weekly Report (MMWR 2015 April 24;64:1-2).

[email protected]

Most accidental genital trauma cases manageable in ED

BY SHARON WORCESTER

AT THE NASPAG ANNUAL MEETING

ORLANDO – Most cases of accidental genital trauma in girls are caused by straddle injuries and are isolated to the labia, and most can be managed expectantly or treated in the emergency department, according to findings from a retrospective cohort study.

Penetrating injuries, however, should be considered an indication for management in the operating room, Dr Tazim Dowlut-McElroy reported at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

A review of 359 cases showed that the vast majority – 82% – were minor and managed expectantly.

“Only 18% required surgical management. Of those, 37% required general anesthesia in the OR, but 63% were adequately evaluated and treated in the ED,” said Dr Dowlut-McElroy of Children’s Mercy Hospitals and Clinics, Kansas City.

About 64% of the patients presented during the day, and 36% presented at night. The most common presenting complaint was bleeding and pain (89% of cases), followed by voiding issues in 8% of cases. No presenting complaint was recorded in the remaining patient charts.

The most common mechanism of injury was straddle injury (73% of cases), followed by non-straddle blunt trauma in 15% of cases, and penetrating injury in the remaining cases, Dr Dowlut-McElroy said.

Injuries included lacerations in 86% of cases, abrasions or contusions in 7%, and hematomas in 3%.

Pediatric genital injuries comprised 0.2%-8% of reported childhood trauma, and despite public health efforts to reduce injuries, the number of such pediatric injuries continues to rise, Dr Dowlut-McElroy said.

Patients included in the current review were identified by a medical database query from January 2000 to July 2014. They were aged 0-18 years and had been treated in the ED for genital trauma; those with obstetrical injuries were excluded. 

[email protected]

EDs pump up pediatric preparedness

BY MARY ANN MOON

FROM JAMA PEDIATRICS

Pediatric readiness has improved in emergency departments across the country, as measured by EDs’ compliance with 2009 guidelines for emergency care in children, according to a report published online April 13 in JAMA Pediatrics.

In what they described as “the most comprehensive evaluation of pediatric readiness of our nation’s EDs to date,” investigators performed a web-based assessment of 4,137 hospitals’ self-reported compliance with guidelines addressing child-specific emergency care. The overall median weighted pediatric readiness score (WPRS) was 68.9, a solid improvement over the previously reported median WPRS of 55, said Dr Marianne Gausche-Hill of Harbor-UCLA Medical Center, Torrance, Calif., and her associates. 

The single most important factor found to enhance pediatric readiness was to designate two people, one of whom is a physician or nurse, as the hospital’s pediatric emergency care coordinator, as recommended by the Institute of Medicine, the researchers wrote. Nearly half (47.5%) of EDs now have a physician coordinator, and 59.3% now have a nurse coordinator, compared with 18% and 12%, respectively, in a previous report. The presence of coordinators quadrupled the chances that a hospital would put important quality-improvement plans in place to address children’s care needs, the investigators said (JAMA Pediatr. 2015 April 13 [doi:10.1001/jamapediatrics.2015.138]).

Other findings included the following:

• Most physicians providing emergency care for children were specifically trained in emergency medicine (88.6%) or pediatric emergency medicine (55.4%) at high-volume hospitals; low-volume hospitals were more likely to have family-medicine-trained physicians doing so (78.9%).
• Mandatory competency evaluations for providing pediatric emergency care were relatively common for nurses (66.6%) but less so for physicians (38.7%) and midlevel staff (18.1%).
• 99.5% of EDs said all staff are trained on the location of pediatric equipment in the ED, including tools to ensure correct sizing of resuscitation equipment and appropriate dosing of medications.
• 83.1% of EDs said they verified the proper location and function of pediatric equipment daily.
• EDs routinely stocked 91% of recommended pediatric equipment. Equipment that was missing in more than 15% of EDs included laryngeal mask airways, umbilical vein catheters, central venous catheters, tracheostomy tubes, size 00 laryngoscope blades, continuous end-tidal carbon dioxide monitoring equipment, pediatric Magill forceps, and infant and child nasopharyngeal airways.
• Only 46.8% of EDs had disaster plans that specifically addressed children, as recommended. Even among high-volume hospitals, which were the most compliant with guidelines, only 67.4% had such disaster plans.
• Approximately one-third of EDs said their providers failed to weigh children and record the weight in kilograms only, as recommended. This safety measure is crucial to preventing drug-dosing errors.
• The most frequently cited barriers to complying with guidelines were the cost of child-specific training (reported by 54.4% of EDs) and a lack of educational resources (reported by 49.0%). Few EDs reported that a lack of interest was a barrier to implementing the guidelines. 

Simplified PESI identified low-risk pulmonary embolism

BY AMY KARON

FROM ACADEMIC EMERGENCY MEDICINE

A simplified version of the Pulmonary Embolism Severity Index identified patients with acute pulmonary embolism who were at low risk of adverse events and might be suitable for outpatient care.

“Although guidelines, such as those from the American College of Chest Physicians, recommend outpatient treatment for selected PE patients at low risk of recurrence, existing evidence for the outpatient management of patients with PE is derived from small cohorts of patients from outside the United States,” said Dr Gregory J. Fermann of the University of Cincinnati department of emergency medicine and his associates.  “Risk stratification of PE patients may allow a cohort of low-risk patients to be treated in a clinical decision unit or by a closely monitored outpatient strategy. Such an approach might relieve some of the burden placed on the emergency department,” they wrote (Acad. Emerg. Med. 2015;22:299-307).

The simplified PESI includes 6 of the 11 variables measured in PESI, which has been shown to identify patients at increased risk of death and adverse outcome events after acute PE. The six features of the simplified PESI are age greater than 80 years, history of cancer, history of chronic cardiopulmonary disease, heart rate of at least 110 beats per minutes, systolic blood pressure less than 100 mm Hg, and oxygen saturation less than 90%. Each factor is assigned a score of 1.

They carried out a post hoc analysis of simplified PESI scores and outcomes among 4,831 acute PE patients from the EINSTEIN-PE study of rivaroxaban  and an enoxaparin–vitamin K antagonist combination (N. Engl. J. Med. 2012;366:1287-97).

Roughly half (53.6%) of the patients had a score of 0, one-third (36.7%) had a score of 1, and 9.7% had a score of 2 or 3, the researchers reported. Higher simplified PESI scores were associated with increased risk of almost all adverse outcomes measured, including recurrent VTE, fatal PE, all-cause mortality, and major bleeding. Patients with scores of 0 or 1 had low rates of major adverse events during the first 30 days of treatment, regardless of which protocol they received. Scores of 2 or 3 were associated with greater risk of recurrent VTE, fatal PE, all-cause mortality, and major bleeding in both treatment groups.

Drug-resistant shigellosis outbreak

BY DEEPAK CHITNIS
FROM MMWR

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

[email protected]

Otherwise healthy patients over 80 benefit from aggressive treatment for MI

BY PATRICE WENDLING
AT ACC/CRF I2 SUMMIT

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41%.

That drop was driven primarily by significantly fewer MIs (17% vs. 30%) and urgent revascularizations (2% vs. 11%), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke or all-cause death.

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%), he reported.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery. The patients were selected from nearly 4,200 elderly patients at 17 community hospitals in Norway; over 3,700 of the patients were ineligible for the study because their life expectancy was less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population, “The coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

[email protected]

FDA approves Anthrasil to treat inhalational anthrax

BY DEEPAK CHITNIS
FRONTLINE MEDICAL NEWS

The Food and Drug Administration has approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), for treatment of inhalational anthrax when used with appropriate antibacterial drugs.

Inhalational anthrax is caused by breathing in Bacillus anthracis spores, which can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of spores. In a statement, Dr. Karen Midthun – director of the FDA’s Center for Biologics Evaluation and Research – explained that Anthrasil “will be stored in U.S. Strategic National Stockpile to facilitate its availability in response to an anthrax emergency.”

Anthrasil was purchased by the U.S. Department of Health & Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in 2011, but because it was not approved, its use prior to FDA approval would have required an emergency use authorization from the FDA.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans, the FDA said. Monkeys and rabbits were exposed to Bacillus anthracis spores, and subsequently given either Anthrasil or a placebo. The survival rate for monkeys given Anthrasil was between 36% and 70%, with a trend toward increased survival at higher doses of Anthrasil. None of the monkeys given placebo survived. Rabbits had a 26% survival rate when given the drug, compared to 2% of those given placebo. A separate study exposed rabbits to Bacillus anthracis and treated them with either antibiotics or a combination of antibiotics and Anthrasil; survival rates were 71% for those treated with the combination and 25% for those treated with antibiotics only.

Safety was tested in 74 healthy human volunteers and the most commonly reported side effects were headache, back pain, nausea, and pain and swelling at the infusion site.

Anthrasil is manufactured by Cangene Corporation, based in Winnipeg, Canada, which developed the drug in collaboration with BARDA.

[email protected]

FDA: Amiodarone plus some hepatitis C antivirals may result in bradycardia

BY ELIZABETH MECHCATIE
Frontline Medical News

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

[email protected]

Clindamycin, TMP-SMX are equally effective for skin infections

BY MARY ANN MOON
FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Clindamycin and trimethoprim-sulfamethoxazole are similarly safe and effective for treating uncomplicated skin infections, including both cellulitis and abscesses, in ambulatory settings in regions where MRSA is endemic.

The data comparing these two agents in an ambulatory setting are limited, though both are commonly recommended as empirical therapy for skin infections in patients who present to clinics and emergency departments and have only minor or no coexisting conditions, said Dr. Loren G. Miller of the Los Angeles Biomedical Research Institute and the division of infectious diseases at Harbor-UCLA Medical Center, and his associates.

They performed a prospective double-blind randomized trial comparing clindamycin against TMP-SMX in 524 ethnically diverse adults and children who presented as outpatients with uncomplicated skin infections during a 2-year period in Chicago, San Francisco, Los Angeles, and Nashville – areas in which community-associated MRSA is endemic. The mean patient age was 27 years, and approximately 30% were pediatric patients. All the participants had cellulitis without abscesses (including erysipelas), one or more abscesses larger than 5 cm in diameter, or both conditions. A total of 264 were randomized to clindamycin and 260 to TMP-SMX daily for 10 days.

Cure rates did not differ significantly between the two study groups. At 7-10 days after completing therapy, the rates of cure in the intention-to-treat population were 80% for clindamycin and 78% for TMP-SMX, and in the evaluable population the rates were nearly 90% and 88%, respectively.

At 1 month follow-up, the cure rates in the evaluable population were 84% for clindamycin and 78% for TMP-SMX, the investigators said (N. Engl. J. Med. 2015;372:1093-103 [doi:10.1056/NEJMoa1403789]). Rates of adverse events were nearly identical between the two study groups at about 19%, and most were mild and resolved without sequelae. There were no treatment-associated serious adverse events, and the rates of treatment discontinuation were similar at nearly 9% between patients receiving clindamycin and those receiving TMP-SMX.

Stroke ambulances speed treatment to U.S. patients

BY MITCHEL L. ZOLER
AT THE INTERNATIONAL STROKE CONFERENCE

NASHVILLE, TENN. – Bringing a CT scanner and thrombolytic treatment directly to stroke patients in the field sped the time to thrombolysis, compared with waiting for the patient to arrive at the hospital.

Some U.S. stroke centers now send out a team that can immediately assess and start treating stroke patients in the community. In 2014, the first two U.S. mobile stroke-treatment units began operating, one in Houston and the second in Cleveland.

Initial reports show both programs were successful in cutting the time to deliver thrombolytic treatment with intravenous tissue plasminogen activator (TPA) to appropriate patients.

In Houston, the active phase of the program started in May 2014, and by October 2014, 47 acute ischemic stroke patients had been treated with TPA. The mobile-unit crews started 43% of eligible patients on thrombolysis within 60 minutes of their symptom onset and another 31% were treated starting 61-80 minutes after symptom onset, said Stephanie A. Parker at the International Stroke Conference.

The unit also treats patients diagnosed with hemorrhagic stroke with intravenous nicardipine for rapid blood pressure reduction, said Ms. Parker, a critical care and emergency medicine–trained registered nurse who is project manager for the Houston mobile unit.

The Cleveland program began in July 2014; of the first 100 stroke patients seen by the mobile unit 16 of 19 eligible patients received tPA, with an average time of 56 minutes from symptom onset to treatment. This compared with an average 94 minutes to tPA onset in patients brought conventionally last year to a Cleveland-area hospital, Dr. M. Shazam Hussain said in a report at the meeting, sponsored by the American Heart Association.

The clinical impact and cost effectiveness of the pilot programs using the mobile units have not yet been assessed from the data, Dr. Hussain and Ms. Parker emphasized. Funding for the Cleveland and Houston vehicles came from local donors; the Houston program also received equipment donations from manufacturers.

The two mobile units are standard 12-foot, box-shaped ambulances outfitted with a CT scanner, a point-of-care lab, and telemedicine components as well as more standard emergency-vehicle equipment. The Houston vehicle contains “all the diagnostic equipment that is in our emergency room,” Ms. Parker said.

The concept behind both the Cleveland unit, operated by the Cleveland Clinic, and the Houston unit, operated by the University of Texas, Houston, is that the mobile stroke unit arrives to a patient with a suspected stroke, the unit is stationary while a CT scan and other diagnostic tests are run, diagnosis occurs with telemedicine assistance. If the patient is cleared for TPA treatment, the infusion starts and the vehicle carries the patient to an appropriate stroke center.

Currently, the Houston unit goes out with a vascular neurologist and a telemedicine physician on board, but plans are in place to test the feasibility of relying entirely on telemedicine when making diagnostic and treatment decisions. The Cleveland mobile unit already operates in this fashion, with no physician on board, and was the first mobile stroke unit in the world to depend completely on telemedicine, according to Dr. Hussain, a neurologist and head of the stroke program at the Cleveland Clinic.

The world’s first mobile stroke unit began operating in Saarland, Germany, in 2008 (Lancet Neurology 2012;11:397-404), and a second unit began running in Berlin after that, Dr. Hussain noted. Because of limited funding, the service he directs in Cleveland has been operating from 8 a.m.-8 p.m., 7 days a week. The program plans to expand to 24-hour coverage. The Houston mobile unit operates 24/7; it averages two runs per day and administers TPA on 1 of every 10 runs, Ms. Parker said. Both the Houston and Cleveland units tie into the local 911 emergency activation systems for their respective regions.

[email protected]

Consider cephalosporin a safe alternative for patients with penicillin allergy

BY DEEPAK CHITNIS
AT THE 2015 AAAAI ANNUAL MEETING

HOUSTON – Given the low incidence of adverse drug reactions to cephalosporin antibiotics among nearly a million California health plan patients, patients with a history of penicillin allergy can safely be given cephalosporins, according to Dr. Eric M. Macy.

The recommendation is based on the findings of a retrospective, population-based analysis of the records of 949,323 Kaiser Permanente Southern California health plan members, which was presented by Dr. Macy, of the Kaiser Permanente Medical Center in San Diego, at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Dr. Macy and his colleagues examined the records of 622,456 health plan members who were given 901,908 regimens of oral cephalosporins and 326,867 members given 487,630 parenteral cephalosporin regimens between Jan. 1, 2010, and Dec. 31, 2012.

Clostridium difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day were the most common cephalosporin-associated adverse drug reactions (ADRs) reported by physicians, with rates of 0.91%, 0.15%, and 0.10%, respectively. Cephalosporin-associated anaphylaxis was documented by physicians a total of five times in oral patients and eight times in parenteral patients (P = .0761), while only three serious cutaneous adverse reactions (SCARs) were recorded. All of those SCARS were attributable to other antibiotics taken at the same time as the cephalosporins, according to Dr. Macy.

Patients who reported developing new cephalosporin allergies over the course of the study period were significantly more likely to be female than male: 0.56% vs. 0.43% (P < .0001). And patients with a history of penicillin allergy were more likely to report a new cephalosporin allergy within 30 days than patients with no drug allergy, another cephalosporin allergy, or a non–beta-lactam allergy.

[email protected]

Drug-resistant shigellosis outbreak

BY DEEPAK CHITNIS
FROM MMWR

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

[email protected]

Otherwise healthy patients over 80 benefit from aggressive treatment for MI

BY PATRICE WENDLING
AT ACC/CRF I2 SUMMIT

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41%.

That drop was driven primarily by significantly fewer MIs (17% vs. 30%) and urgent revascularizations (2% vs. 11%), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke or all-cause death.

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%), he reported.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery. The patients were selected from nearly 4,200 elderly patients at 17 community hospitals in Norway; over 3,700 of the patients were ineligible for the study because their life expectancy was less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population, “The coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

[email protected]

FDA approves Anthrasil to treat inhalational anthrax

BY DEEPAK CHITNIS
FRONTLINE MEDICAL NEWS

The Food and Drug Administration has approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), for treatment of inhalational anthrax when used with appropriate antibacterial drugs.

Inhalational anthrax is caused by breathing in Bacillus anthracis spores, which can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of spores. In a statement, Dr. Karen Midthun – director of the FDA’s Center for Biologics Evaluation and Research – explained that Anthrasil “will be stored in U.S. Strategic National Stockpile to facilitate its availability in response to an anthrax emergency.”

Anthrasil was purchased by the U.S. Department of Health & Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in 2011, but because it was not approved, its use prior to FDA approval would have required an emergency use authorization from the FDA.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans, the FDA said. Monkeys and rabbits were exposed to Bacillus anthracis spores, and subsequently given either Anthrasil or a placebo. The survival rate for monkeys given Anthrasil was between 36% and 70%, with a trend toward increased survival at higher doses of Anthrasil. None of the monkeys given placebo survived. Rabbits had a 26% survival rate when given the drug, compared to 2% of those given placebo. A separate study exposed rabbits to Bacillus anthracis and treated them with either antibiotics or a combination of antibiotics and Anthrasil; survival rates were 71% for those treated with the combination and 25% for those treated with antibiotics only.

Safety was tested in 74 healthy human volunteers and the most commonly reported side effects were headache, back pain, nausea, and pain and swelling at the infusion site.

Anthrasil is manufactured by Cangene Corporation, based in Winnipeg, Canada, which developed the drug in collaboration with BARDA.

[email protected]

FDA: Amiodarone plus some hepatitis C antivirals may result in bradycardia

BY ELIZABETH MECHCATIE
Frontline Medical News

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

[email protected]

Clindamycin, TMP-SMX are equally effective for skin infections

BY MARY ANN MOON
FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Clindamycin and trimethoprim-sulfamethoxazole are similarly safe and effective for treating uncomplicated skin infections, including both cellulitis and abscesses, in ambulatory settings in regions where MRSA is endemic.

The data comparing these two agents in an ambulatory setting are limited, though both are commonly recommended as empirical therapy for skin infections in patients who present to clinics and emergency departments and have only minor or no coexisting conditions, said Dr. Loren G. Miller of the Los Angeles Biomedical Research Institute and the division of infectious diseases at Harbor-UCLA Medical Center, and his associates.

They performed a prospective double-blind randomized trial comparing clindamycin against TMP-SMX in 524 ethnically diverse adults and children who presented as outpatients with uncomplicated skin infections during a 2-year period in Chicago, San Francisco, Los Angeles, and Nashville – areas in which community-associated MRSA is endemic. The mean patient age was 27 years, and approximately 30% were pediatric patients. All the participants had cellulitis without abscesses (including erysipelas), one or more abscesses larger than 5 cm in diameter, or both conditions. A total of 264 were randomized to clindamycin and 260 to TMP-SMX daily for 10 days.

Cure rates did not differ significantly between the two study groups. At 7-10 days after completing therapy, the rates of cure in the intention-to-treat population were 80% for clindamycin and 78% for TMP-SMX, and in the evaluable population the rates were nearly 90% and 88%, respectively.

At 1 month follow-up, the cure rates in the evaluable population were 84% for clindamycin and 78% for TMP-SMX, the investigators said (N. Engl. J. Med. 2015;372:1093-103 [doi:10.1056/NEJMoa1403789]). Rates of adverse events were nearly identical between the two study groups at about 19%, and most were mild and resolved without sequelae. There were no treatment-associated serious adverse events, and the rates of treatment discontinuation were similar at nearly 9% between patients receiving clindamycin and those receiving TMP-SMX.

Stroke ambulances speed treatment to U.S. patients

BY MITCHEL L. ZOLER
AT THE INTERNATIONAL STROKE CONFERENCE

NASHVILLE, TENN. – Bringing a CT scanner and thrombolytic treatment directly to stroke patients in the field sped the time to thrombolysis, compared with waiting for the patient to arrive at the hospital.

Some U.S. stroke centers now send out a team that can immediately assess and start treating stroke patients in the community. In 2014, the first two U.S. mobile stroke-treatment units began operating, one in Houston and the second in Cleveland.

Initial reports show both programs were successful in cutting the time to deliver thrombolytic treatment with intravenous tissue plasminogen activator (TPA) to appropriate patients.

In Houston, the active phase of the program started in May 2014, and by October 2014, 47 acute ischemic stroke patients had been treated with TPA. The mobile-unit crews started 43% of eligible patients on thrombolysis within 60 minutes of their symptom onset and another 31% were treated starting 61-80 minutes after symptom onset, said Stephanie A. Parker at the International Stroke Conference.

The unit also treats patients diagnosed with hemorrhagic stroke with intravenous nicardipine for rapid blood pressure reduction, said Ms. Parker, a critical care and emergency medicine–trained registered nurse who is project manager for the Houston mobile unit.

The Cleveland program began in July 2014; of the first 100 stroke patients seen by the mobile unit 16 of 19 eligible patients received tPA, with an average time of 56 minutes from symptom onset to treatment. This compared with an average 94 minutes to tPA onset in patients brought conventionally last year to a Cleveland-area hospital, Dr. M. Shazam Hussain said in a report at the meeting, sponsored by the American Heart Association.

The clinical impact and cost effectiveness of the pilot programs using the mobile units have not yet been assessed from the data, Dr. Hussain and Ms. Parker emphasized. Funding for the Cleveland and Houston vehicles came from local donors; the Houston program also received equipment donations from manufacturers.

The two mobile units are standard 12-foot, box-shaped ambulances outfitted with a CT scanner, a point-of-care lab, and telemedicine components as well as more standard emergency-vehicle equipment. The Houston vehicle contains “all the diagnostic equipment that is in our emergency room,” Ms. Parker said.

The concept behind both the Cleveland unit, operated by the Cleveland Clinic, and the Houston unit, operated by the University of Texas, Houston, is that the mobile stroke unit arrives to a patient with a suspected stroke, the unit is stationary while a CT scan and other diagnostic tests are run, diagnosis occurs with telemedicine assistance. If the patient is cleared for TPA treatment, the infusion starts and the vehicle carries the patient to an appropriate stroke center.

Currently, the Houston unit goes out with a vascular neurologist and a telemedicine physician on board, but plans are in place to test the feasibility of relying entirely on telemedicine when making diagnostic and treatment decisions. The Cleveland mobile unit already operates in this fashion, with no physician on board, and was the first mobile stroke unit in the world to depend completely on telemedicine, according to Dr. Hussain, a neurologist and head of the stroke program at the Cleveland Clinic.

The world’s first mobile stroke unit began operating in Saarland, Germany, in 2008 (Lancet Neurology 2012;11:397-404), and a second unit began running in Berlin after that, Dr. Hussain noted. Because of limited funding, the service he directs in Cleveland has been operating from 8 a.m.-8 p.m., 7 days a week. The program plans to expand to 24-hour coverage. The Houston mobile unit operates 24/7; it averages two runs per day and administers TPA on 1 of every 10 runs, Ms. Parker said. Both the Houston and Cleveland units tie into the local 911 emergency activation systems for their respective regions.

[email protected]

Consider cephalosporin a safe alternative for patients with penicillin allergy

BY DEEPAK CHITNIS
AT THE 2015 AAAAI ANNUAL MEETING

HOUSTON – Given the low incidence of adverse drug reactions to cephalosporin antibiotics among nearly a million California health plan patients, patients with a history of penicillin allergy can safely be given cephalosporins, according to Dr. Eric M. Macy.

The recommendation is based on the findings of a retrospective, population-based analysis of the records of 949,323 Kaiser Permanente Southern California health plan members, which was presented by Dr. Macy, of the Kaiser Permanente Medical Center in San Diego, at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Dr. Macy and his colleagues examined the records of 622,456 health plan members who were given 901,908 regimens of oral cephalosporins and 326,867 members given 487,630 parenteral cephalosporin regimens between Jan. 1, 2010, and Dec. 31, 2012.

Clostridium difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day were the most common cephalosporin-associated adverse drug reactions (ADRs) reported by physicians, with rates of 0.91%, 0.15%, and 0.10%, respectively. Cephalosporin-associated anaphylaxis was documented by physicians a total of five times in oral patients and eight times in parenteral patients (P = .0761), while only three serious cutaneous adverse reactions (SCARs) were recorded. All of those SCARS were attributable to other antibiotics taken at the same time as the cephalosporins, according to Dr. Macy.

Patients who reported developing new cephalosporin allergies over the course of the study period were significantly more likely to be female than male: 0.56% vs. 0.43% (P < .0001). And patients with a history of penicillin allergy were more likely to report a new cephalosporin allergy within 30 days than patients with no drug allergy, another cephalosporin allergy, or a non–beta-lactam allergy.

[email protected]

Drug-resistant shigellosis outbreak

BY DEEPAK CHITNIS
FROM MMWR

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

[email protected]

Otherwise healthy patients over 80 benefit from aggressive treatment for MI

BY PATRICE WENDLING
AT ACC/CRF I2 SUMMIT

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41%.

That drop was driven primarily by significantly fewer MIs (17% vs. 30%) and urgent revascularizations (2% vs. 11%), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke or all-cause death.

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%), he reported.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery. The patients were selected from nearly 4,200 elderly patients at 17 community hospitals in Norway; over 3,700 of the patients were ineligible for the study because their life expectancy was less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population, “The coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

[email protected]

FDA approves Anthrasil to treat inhalational anthrax

BY DEEPAK CHITNIS
FRONTLINE MEDICAL NEWS

The Food and Drug Administration has approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), for treatment of inhalational anthrax when used with appropriate antibacterial drugs.

Inhalational anthrax is caused by breathing in Bacillus anthracis spores, which can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of spores. In a statement, Dr. Karen Midthun – director of the FDA’s Center for Biologics Evaluation and Research – explained that Anthrasil “will be stored in U.S. Strategic National Stockpile to facilitate its availability in response to an anthrax emergency.”

Anthrasil was purchased by the U.S. Department of Health & Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in 2011, but because it was not approved, its use prior to FDA approval would have required an emergency use authorization from the FDA.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans, the FDA said. Monkeys and rabbits were exposed to Bacillus anthracis spores, and subsequently given either Anthrasil or a placebo. The survival rate for monkeys given Anthrasil was between 36% and 70%, with a trend toward increased survival at higher doses of Anthrasil. None of the monkeys given placebo survived. Rabbits had a 26% survival rate when given the drug, compared to 2% of those given placebo. A separate study exposed rabbits to Bacillus anthracis and treated them with either antibiotics or a combination of antibiotics and Anthrasil; survival rates were 71% for those treated with the combination and 25% for those treated with antibiotics only.

Safety was tested in 74 healthy human volunteers and the most commonly reported side effects were headache, back pain, nausea, and pain and swelling at the infusion site.

Anthrasil is manufactured by Cangene Corporation, based in Winnipeg, Canada, which developed the drug in collaboration with BARDA.

[email protected]

FDA: Amiodarone plus some hepatitis C antivirals may result in bradycardia

BY ELIZABETH MECHCATIE
Frontline Medical News

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

[email protected]

Clindamycin, TMP-SMX are equally effective for skin infections

BY MARY ANN MOON
FROM THE NEW ENGLAND JOURNAL OF MEDICINE