News & Analysis
though guidelines say it’s a second-line agent for lowering cholesterol, reflects Jackevicius’s team’s findings. Using data from provincial health administrative databases, the Saskatchewan researchers found that ezetimibe prescriptions were 2.5% of cholesterol-lowering dispensations in 2004 and 8.8% of such dispensations in 2011 (Alsabbagh WM et al. Can J Cardiol. 2014; 30[2]:237-243). The authors concluded that allowing unrestricted use of ezetimibe in Saskatchewan may have led to a large number of inappropriate prescriptions, at odds with Canadian clinical guidelines. And although ezetimibe use declined in the United States, its use per 100 000 population is still greater than Canada’s, generat-
ing US expenditures of more than $2.2 billion in 2009. Krumholz, one of the coauthors on the study with Jackevicius, remains perplexed as to the continuing popularity of ezetimibe. “The drug continues to defy gravity, and that’s probably a result of really strong marketing and the singular focus on cholesterol numbers,” he said. Krumholz said heart health campaigns urging patients to “know your numbers” and treatment goals based on cholesterol measurements, such as getting asymptomatic individuals’LDL-Clevelsbelow130mg/dL,have worked in ezetimibe’s favor at the expense of evidence-based medicine. “Is this the drug that lowers your LDL-C and helps you? We
don’t know that,” he said. “The comfort of hitting a target offers little benefit if you don’t know that it is really protecting you.” Although ENHANCE has not derailed ezetimibe prescribing, the newest cholesterol management guidelines just might. The guidelines, issued late last year by the American College of Cardiology and the American Heart Association, abandon the idea of reaching a target level for LDL-C, instead recommending the use of statins to reduce LDL-C levels only for certain types of patients. Will this change in the guidelines affect ezetimibe prescribing? “It will be interesting to see what the guidelines will do,” Krumholz said.
Poliolike Cases Probed in California CDC Says Rare Cases Not Cause for Widespread Alarm Bridget M. Kuehn, MSJ
K
eith Van Haren, MD, a pediatric neurologist at the Lucile Packard Children’s Hospital at Stanford University, is accustomed to seeing children who present with rare cases of sudden-onset paralysis. These rare but serious emergencies can have a range of causes, including GuillainBarré syndrome, botulism, or tick paralysis.
In 2012, Van Haren and his colleagues across the state noticed an unusual trend of cases of sudden-onset acute flaccid paralysis with motor neuron injury. Normally, he and his colleagues can expect to see 1 such case a year, he said. But in the autumn of 2012, 2 cases of this rare combination were seen, and a few more cases quickly followed.
Later this month, Van Haren and his colleagues will present data for 5 of the cases at the American Academy of Neurology’s annual meeting. But release of the abstract in February generated considerable media attention. “The physician community is taking this very seriously and is invested in figuring out the cause,” Van Haren cautioned. “But it remains rare.” Benjamin Haynes, a spokesperson at the Centers for Disease Control and Prevention (CDC), said the agency is closely monitoring the situation and has consulted with officials from the California Department of Public Health. “At this time, CDC does not think the situation in California poses a public health threat, but we encourage parents to speak with their doctors or pediatricians if they have concerns,” he said.
Seeking an Explanation
Twenty cases of a poliolike illness in California have prompted concerns, but the US Centers for Disease Control and Prevention say the infections are unlikely to pose a public health threat.
1280
Emmanuelle Waubant, MD, PhD, a neurologist at the University of California, San Francisco and one of the abstract’s coauthors, said she and her colleagues wanted to bring the cases to the attention of other neurologists and the California Department of Public Health to encourage quick testing of samples for infectious agents.
JAMA April 2, 2014 Volume 311, Number 13
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/23/2015
jama.com
News & Analysis
Centers for Disease Control and Prevention
Several of the cases had been misdiagnosed as transverse myelitis, she said. Two nasal samples from children with the condition have tested positive for enterovirus 68, a pathogen previously associated with respirator y illness. Waubant said the virus was not detected in some other patients, although it may have simply been too late in the course of illness to be found. “We are not 100% sure there is a causal relationship with enterovirus 68 and poliolike symptoms,” she said. But finding this enterovirus is concerning because it belongs to the same family of viruses as the poliovirus and has in some rare cases been linked to serious illnesses in the past. According to the CDC, enteroviruses are a common cause of human infection but rarely cause symptoms. In a 2011 report, the agency documented several clusters of respiratory illness in Asia, Europe, and the United States between 2008 and 2010, including some hospitalizations and deaths, linked to enterovirus 68 (Imamura T et al. MMWR Morb Mortal Wkly Rep. 2011;60[38]:1301-1304). In this report, the CDC noted the whole range of enterovirus 68 illness is not clear and that this virus has been linked with neurologic disease in at least 1 case (Kreuter JD et al. Arch Pathol Laboratory Med. 2011;135:793796). But the agency urged clinicians
Not a Cause for Alarm
There is some disagreement about whether the 20 cases reported so far fall outside normal baseline levels. Haynes noted in a written statement that “considering the minimum expected rate of acute flaccid paralysis cases in the population annually, the number of cases reported to be under investigation by California Department of Public Health are well within the expected rate.” He also explained that the expected rate of nonpolio acute flaccid paralysis is at least 1 per 100 000 children each year, according to the World Health Organization’s standards for polio surveillance. By this standard, at least 78 cases would be expected in California each year. Acute flaccid paralysis is not a condition that clinicians are required to report to the CDC, so the agency is “unable to assess the significance of the small numbers of cases reported by local and state health departments or speak on a national level, ” Haynes said. But Van Haren said he and his colleagues feel that this particular presentation of acute flaccid paralysis with motor neuron injury is occurring at levels higher than baseline. He explained that there are also other reasons to be concerned about this particular subset of patients. But he and his colleagues have seen more severe disability and less recovery in this group of patients than they would expec t with most cases of acute flaccid “The physician community is taking paralysis. this very seriously and is invested in There has not been any apfiguring out the cause. But it remains parent connecrare.”—Keith Van Haren, MD tion between the cases, and Van Haren and to be aware that this virus was a possible Waubant agree that there is no immediate cause of respiratory illness and to report cause for public health concern. clusters of unexplained respiratory illVan Haren suggested that physicians nesses to local public health authorities. consider the possibility of a motor neuron inGil Chavez, MD, MPH, director of the jury when evaluating patients with a rapid center for infectious disease at the Califor- onset of paralysis, particularly if they are connia Department of Public Health, said in a sidering a diagnosis of transverse myelitis. statement that the department has tested Waubant said when a patient presents with specimens from 15 of the 20 reported severe or moderate poliolike symptoms, cases so far and has not found any com- physicians should consider a possible infecmon cause. He said the department will tious cause and send clinical specimens to continue to investigate. the appropriate public health officials.
news@JAMA FROM JAMA’S DAILY NEWS SITE
Toxin May Be Factor in Multiple Sclerosis A toxin produced by a ubiquitous bacteria and common source of food poisoning can damage the same cells that are attacked in patients with multiple sclerosis (MS). Clostridium perfringens type B is commonly found in soil and human and animal intestines, but certain subtypes (B and D) produce a chemical that may become toxic when ingested. The toxin kills oligodendrocytes and binds to many of the sites where inflammation is seen in patients with MS. This suggests a mechanism by which the toxin might contribute to the disease. Patients with active MS are also more likely to have antibodies to the toxin compared with healthy individuals. http://jama.md/1kBdD4L New Harms of Smoking Still Emerging Fifty years after the 1964 landmark general’s report on the negative health effects of smoking, research continues to reinforce the report’s findings. The recently released 2014 surgeon general’s report on the health effects of smoking highlights new evidence that smoking causes liver cancer, colon cancer, diabetes, and rheumatoid arthritis and that secondhand smoke causes stroke. The report also noted that women are now as likely as men to die from smoking-related diseases. http://jama.md/1hsHnfH Less Aggressive Treatment for Diverticulitis Recent research suggests that recommendations offered in current national clinical guidelines for treating patients with sigmoid diverticulitis may overstate the need for aggressive antibiotic and surgical interventions. Researchers conducted a systematic review in which they analyzed 80 articles regarding the diagnosis and management of diverticulitis published between January 1, 2000, and March 31, 2013. They found, contrary to previous thought, that the risk of septic peritonitis is reduced rather than increased with each recurrence of diverticulitis. Their analysis also found that treatment with antibiotics and fiber consumption were not as beneficial as previously thought and that surgery for chronic disease is not always warranted. http://jama.md/NCemVm
jama.com
For more on these stories and other medical news, visit http://newsatjama.jama.com. JAMA April 2, 2014 Volume 311, Number 13
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/23/2015
1281
though guidelines say it’s a second-line agent for lowering cholesterol, reflects Jackevicius’s team’s findings. Using data from provincial health administrative databases, the Saskatchewan researchers found that ezetimibe prescriptions were 2.5% of cholesterol-lowering dispensations in 2004 and 8.8% of such dispensations in 2011 (Alsabbagh WM et al. Can J Cardiol. 2014; 30[2]:237-243). The authors concluded that allowing unrestricted use of ezetimibe in Saskatchewan may have led to a large number of inappropriate prescriptions, at odds with Canadian clinical guidelines. And although ezetimibe use declined in the United States, its use per 100 000 population is still greater than Canada’s, generat-
ing US expenditures of more than $2.2 billion in 2009. Krumholz, one of the coauthors on the study with Jackevicius, remains perplexed as to the continuing popularity of ezetimibe. “The drug continues to defy gravity, and that’s probably a result of really strong marketing and the singular focus on cholesterol numbers,” he said. Krumholz said heart health campaigns urging patients to “know your numbers” and treatment goals based on cholesterol measurements, such as getting asymptomatic individuals’LDL-Clevelsbelow130mg/dL,have worked in ezetimibe’s favor at the expense of evidence-based medicine. “Is this the drug that lowers your LDL-C and helps you? We
don’t know that,” he said. “The comfort of hitting a target offers little benefit if you don’t know that it is really protecting you.” Although ENHANCE has not derailed ezetimibe prescribing, the newest cholesterol management guidelines just might. The guidelines, issued late last year by the American College of Cardiology and the American Heart Association, abandon the idea of reaching a target level for LDL-C, instead recommending the use of statins to reduce LDL-C levels only for certain types of patients. Will this change in the guidelines affect ezetimibe prescribing? “It will be interesting to see what the guidelines will do,” Krumholz said.
Poliolike Cases Probed in California CDC Says Rare Cases Not Cause for Widespread Alarm Bridget M. Kuehn, MSJ
K
eith Van Haren, MD, a pediatric neurologist at the Lucile Packard Children’s Hospital at Stanford University, is accustomed to seeing children who present with rare cases of sudden-onset paralysis. These rare but serious emergencies can have a range of causes, including GuillainBarré syndrome, botulism, or tick paralysis.
In 2012, Van Haren and his colleagues across the state noticed an unusual trend of cases of sudden-onset acute flaccid paralysis with motor neuron injury. Normally, he and his colleagues can expect to see 1 such case a year, he said. But in the autumn of 2012, 2 cases of this rare combination were seen, and a few more cases quickly followed.
Later this month, Van Haren and his colleagues will present data for 5 of the cases at the American Academy of Neurology’s annual meeting. But release of the abstract in February generated considerable media attention. “The physician community is taking this very seriously and is invested in figuring out the cause,” Van Haren cautioned. “But it remains rare.” Benjamin Haynes, a spokesperson at the Centers for Disease Control and Prevention (CDC), said the agency is closely monitoring the situation and has consulted with officials from the California Department of Public Health. “At this time, CDC does not think the situation in California poses a public health threat, but we encourage parents to speak with their doctors or pediatricians if they have concerns,” he said.
Seeking an Explanation
Twenty cases of a poliolike illness in California have prompted concerns, but the US Centers for Disease Control and Prevention say the infections are unlikely to pose a public health threat.
1280
Emmanuelle Waubant, MD, PhD, a neurologist at the University of California, San Francisco and one of the abstract’s coauthors, said she and her colleagues wanted to bring the cases to the attention of other neurologists and the California Department of Public Health to encourage quick testing of samples for infectious agents.
JAMA April 2, 2014 Volume 311, Number 13
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/23/2015
jama.com
News & Analysis
Centers for Disease Control and Prevention
Several of the cases had been misdiagnosed as transverse myelitis, she said. Two nasal samples from children with the condition have tested positive for enterovirus 68, a pathogen previously associated with respirator y illness. Waubant said the virus was not detected in some other patients, although it may have simply been too late in the course of illness to be found. “We are not 100% sure there is a causal relationship with enterovirus 68 and poliolike symptoms,” she said. But finding this enterovirus is concerning because it belongs to the same family of viruses as the poliovirus and has in some rare cases been linked to serious illnesses in the past. According to the CDC, enteroviruses are a common cause of human infection but rarely cause symptoms. In a 2011 report, the agency documented several clusters of respiratory illness in Asia, Europe, and the United States between 2008 and 2010, including some hospitalizations and deaths, linked to enterovirus 68 (Imamura T et al. MMWR Morb Mortal Wkly Rep. 2011;60[38]:1301-1304). In this report, the CDC noted the whole range of enterovirus 68 illness is not clear and that this virus has been linked with neurologic disease in at least 1 case (Kreuter JD et al. Arch Pathol Laboratory Med. 2011;135:793796). But the agency urged clinicians
Not a Cause for Alarm
There is some disagreement about whether the 20 cases reported so far fall outside normal baseline levels. Haynes noted in a written statement that “considering the minimum expected rate of acute flaccid paralysis cases in the population annually, the number of cases reported to be under investigation by California Department of Public Health are well within the expected rate.” He also explained that the expected rate of nonpolio acute flaccid paralysis is at least 1 per 100 000 children each year, according to the World Health Organization’s standards for polio surveillance. By this standard, at least 78 cases would be expected in California each year. Acute flaccid paralysis is not a condition that clinicians are required to report to the CDC, so the agency is “unable to assess the significance of the small numbers of cases reported by local and state health departments or speak on a national level, ” Haynes said. But Van Haren said he and his colleagues feel that this particular presentation of acute flaccid paralysis with motor neuron injury is occurring at levels higher than baseline. He explained that there are also other reasons to be concerned about this particular subset of patients. But he and his colleagues have seen more severe disability and less recovery in this group of patients than they would expec t with most cases of acute flaccid “The physician community is taking paralysis. this very seriously and is invested in There has not been any apfiguring out the cause. But it remains parent connecrare.”—Keith Van Haren, MD tion between the cases, and Van Haren and to be aware that this virus was a possible Waubant agree that there is no immediate cause of respiratory illness and to report cause for public health concern. clusters of unexplained respiratory illVan Haren suggested that physicians nesses to local public health authorities. consider the possibility of a motor neuron inGil Chavez, MD, MPH, director of the jury when evaluating patients with a rapid center for infectious disease at the Califor- onset of paralysis, particularly if they are connia Department of Public Health, said in a sidering a diagnosis of transverse myelitis. statement that the department has tested Waubant said when a patient presents with specimens from 15 of the 20 reported severe or moderate poliolike symptoms, cases so far and has not found any com- physicians should consider a possible infecmon cause. He said the department will tious cause and send clinical specimens to continue to investigate. the appropriate public health officials.
news@JAMA FROM JAMA’S DAILY NEWS SITE
Toxin May Be Factor in Multiple Sclerosis A toxin produced by a ubiquitous bacteria and common source of food poisoning can damage the same cells that are attacked in patients with multiple sclerosis (MS). Clostridium perfringens type B is commonly found in soil and human and animal intestines, but certain subtypes (B and D) produce a chemical that may become toxic when ingested. The toxin kills oligodendrocytes and binds to many of the sites where inflammation is seen in patients with MS. This suggests a mechanism by which the toxin might contribute to the disease. Patients with active MS are also more likely to have antibodies to the toxin compared with healthy individuals. http://jama.md/1kBdD4L New Harms of Smoking Still Emerging Fifty years after the 1964 landmark general’s report on the negative health effects of smoking, research continues to reinforce the report’s findings. The recently released 2014 surgeon general’s report on the health effects of smoking highlights new evidence that smoking causes liver cancer, colon cancer, diabetes, and rheumatoid arthritis and that secondhand smoke causes stroke. The report also noted that women are now as likely as men to die from smoking-related diseases. http://jama.md/1hsHnfH Less Aggressive Treatment for Diverticulitis Recent research suggests that recommendations offered in current national clinical guidelines for treating patients with sigmoid diverticulitis may overstate the need for aggressive antibiotic and surgical interventions. Researchers conducted a systematic review in which they analyzed 80 articles regarding the diagnosis and management of diverticulitis published between January 1, 2000, and March 31, 2013. They found, contrary to previous thought, that the risk of septic peritonitis is reduced rather than increased with each recurrence of diverticulitis. Their analysis also found that treatment with antibiotics and fiber consumption were not as beneficial as previously thought and that surgery for chronic disease is not always warranted. http://jama.md/NCemVm
jama.com
For more on these stories and other medical news, visit http://newsatjama.jama.com. JAMA April 2, 2014 Volume 311, Number 13
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/23/2015
1281
