Neuromuscular Disorders

VANCOUVER – A new American Academy of Neurology practice guideline on the efficacy and safety evidence for botulinum toxin treatment of blepharospasm, cervical dystonia, spasticity, and headache has updated the last recommendations published in 2008, but leaves some relevant clinical concerns and off-label uses unaddressed.

The 2016 update, published April 18 in Neurology, adds new individual evidence for the use of the four branded formulations of the two commercially available botulinum toxin serotypes, A and B, for the aforementioned indications rather than lumping all recommendations for botulinum toxin together as in the 2008 guidelines. However, questions remain on the differences between the different products in clinical practice, especially since the formulations show little clinical difference in head-to-head comparisons for some of the indications, especially for the serotype A formulations.

Jeff Evans/Frontline Medical News

In a press briefing on the new guidelines at the annual meeting of the American Academy of Neurology, guidelines coauthor Dr. Mark Hallett noted that nothing really surprised the experienced 14-member committee that put the guidelines together. “The reason that we chose these four different diseases is because we already had the sense that they were going to change in the particular ways that they did. We didn’t know exactly, of course, what was going to happen, but we had a sense that there were sufficient data that it was worth looking at them.”

For blepharospasm, the totality of evidence suggests that onabotulinumtoxinA (onaBoNT-A; Botox) and incobotulinumtoxinA (incoBoNT-A; Xeomin) injections should be considered and are probably safe and effective (level B recommendation), while abobotulinumtoxinA (aboBoNT-A; Dysport) may be considered (level C) and is possibly effective. The evidence shows that incoBoNT-A and onaBoNT-A have equivalent efficacy and aboBoNT-A and onaBoNT-A are possibly equivalent. There was not enough evidence to determine the efficacy of rimabotulinumtoxinB for blepharospasm (rimaBoNT-B; Myobloc).

The rigorousness of clinical trials in evaluating the efficacy and safety of botulinum toxin has evolved since the Food and Drug Administration approved onaBoNT-A and incoBoNT-A to treat blepharospasm, but no new trials have been conducted to give it a higher level of recommendation despite their well-known magnitude of benefit, said Dr. Hallett, chief of the National Institute of Neurological Disorders and Stroke medical neurology branch and its human motor control section.

New evidence added to the already well-established data on the effectiveness of botulinum toxin for cervical dystonia suggest that onaBoNT-A and incoBoNT-A are probably safe and effective and should be considered. In addition, aboBoNT-A and rimaBoNT-B have already proven effectiveness and safety and should be offered. The lack of class I studies for onaBoNT-A and incoBoNT-A led to the lower level of recommendation for them despite an extensive clinical history of their use in cervical dystonia, the guideline committee wrote (Neurology. 2016 Apr 18. doi: 10.1212/WNL.0000000000002560).

In adults with upper-limb spasticity, all three serotype A formulations – onaBoNT-A, aboBoNT-A, and incoBoNT-A – are effective and safe in reducing symptoms and improving passive limb function. All three achieved level A evidence to recommend that they should be offered. One comparative trial showed enough evidence to say that onaBoNT-A is probably superior to tizanidine for reducing upper-extremity tone and should be considered before it. RimaBoNT-B has level B evidence to advise that it should be considered and is probably safe and effective. None of the formulations have enough data to determine their efficacy on active limb function.

Fewer trials have examined the safety and effectiveness of botulinum toxin formulations for reducing lower leg spasticity in adults. The guidelines panel found enough evidence to recommend that aboBoNT-A and onaBoNT-A are safe and effective and should be offered (level A). There were no trials with high enough level of quality to determine whether incoBoNT-A or rimaBoNT-B were effective for lower-leg spasticity. None of the four agents had enough evidence to support their ability to improve active function associated with lower-limb spasticity.

At the press briefing, guidelines first author Dr. David M. Simpson expressed hope that a more refined methodology for evaluating spasticity might be achieved in future trials of botulinum toxin to detect the potentially subtle effects the agents may have on certain patients who are more likely to achieve benefits in active limb function. Currently, trials use a standardized set of outcomes to try to detect differences in patients with wide-ranging severity of symptoms and types of injury that led to spasticity. Dr. Simpson is professor of neurology at Mount Sinai in New York, as well as director of the neuromuscular diseases division and director of the clinical neurophysiology laboratories.

Positive results for onaBoNT-A in two pivotal trials in chronic migraine that were published since the last guidelines give the formulation the only FDA-approved indication for a botulinum toxin in chronic migraine and earned it a level A recommendation from the guidelines committee. However, in the trials it had a relatively small magnitude of efficacy in reducing the number of headache days by 15% versus placebo. The guidelines also advise not using onaBoNT-A in episodic migraine based on three negative trials. No high-quality trials have evaluated any formulation to change the overall 2008 guidelines’ advice that botulinum toxin is probably ineffective for treating chronic tension-type headaches.

Familiarity with appropriate dosing and side effects may allow clinicians to use the products off-label for indications in the guidelines for which clinical trials were not available, Dr. Richard L. Barbano of the movement disorders division at the University of Rochester noted in an editorial about the guidelines (Neurol Clin Pract. 2016 Apr 18. doi: 10.1212/CPJ.0000000000000244). “Off-label use is common in clinical practice. Little data exist to indicate that any of the different formulations, with attention to appropriate dosing and side effects, would not be effective in treating these other conditions. There are also a number of other neurologic conditions not discussed in the guideline in which botulinum toxin has shown efficacy, such as hemifacial spasm and other focal dystonias. Lack of sufficient high-level evidence to support a level A or B guideline recommendation does not negate their potential utility and likewise, there is little evidence to recommend one formulation over another.”

“In some circumstances where the drugs are relatively equivalent, some people prefer to stick with one so they get used to it more, and they can have more of a sense of what the dosing is, given that the doses may be different with the compounds and have different side effects,” Dr. Hallett said in an interview, noting that availability and price also might enter into a clinician’s decision on what to do.

Dr. Barbano also said that cost and value are becoming more important, and neurologists should consider when botulinum toxin therapy should be chosen among existing alternative treatment options, particularly for chronic migraine.

The guidelines are endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine and the American Society of Plastic Surgeons.

Dr. Hallett reported serving as chair of the Neurotoxin Institute Advisory Council and has received research grants from Allergan and Merz Pharmaceuticals. Dr. Simpson reported receiving research grants from and served as a consultant for Allergan, Ipsen, Merz Pharmaceuticals, and Acorda Therapeutics. Five other coauthors of the guidelines disclosed relationships with manufacturers of botulinum toxin formulations. Dr. Barbano reported serving on a scientific advisory board for Allergan and receiving research support from Allergan, Vaccinex, and Biotie.

[email protected]

VANCOUVER – A new American Academy of Neurology practice guideline on the efficacy and safety evidence for botulinum toxin treatment of blepharospasm, cervical dystonia, spasticity, and headache has updated the last recommendations published in 2008, but leaves some relevant clinical concerns and off-label uses unaddressed.

The 2016 update, published April 18 in Neurology, adds new individual evidence for the use of the four branded formulations of the two commercially available botulinum toxin serotypes, A and B, for the aforementioned indications rather than lumping all recommendations for botulinum toxin together as in the 2008 guidelines. However, questions remain on the differences between the different products in clinical practice, especially since the formulations show little clinical difference in head-to-head comparisons for some of the indications, especially for the serotype A formulations.

Jeff Evans/Frontline Medical News

In a press briefing on the new guidelines at the annual meeting of the American Academy of Neurology, guidelines coauthor Dr. Mark Hallett noted that nothing really surprised the experienced 14-member committee that put the guidelines together. “The reason that we chose these four different diseases is because we already had the sense that they were going to change in the particular ways that they did. We didn’t know exactly, of course, what was going to happen, but we had a sense that there were sufficient data that it was worth looking at them.”

For blepharospasm, the totality of evidence suggests that onabotulinumtoxinA (onaBoNT-A; Botox) and incobotulinumtoxinA (incoBoNT-A; Xeomin) injections should be considered and are probably safe and effective (level B recommendation), while abobotulinumtoxinA (aboBoNT-A; Dysport) may be considered (level C) and is possibly effective. The evidence shows that incoBoNT-A and onaBoNT-A have equivalent efficacy and aboBoNT-A and onaBoNT-A are possibly equivalent. There was not enough evidence to determine the efficacy of rimabotulinumtoxinB for blepharospasm (rimaBoNT-B; Myobloc).

The rigorousness of clinical trials in evaluating the efficacy and safety of botulinum toxin has evolved since the Food and Drug Administration approved onaBoNT-A and incoBoNT-A to treat blepharospasm, but no new trials have been conducted to give it a higher level of recommendation despite their well-known magnitude of benefit, said Dr. Hallett, chief of the National Institute of Neurological Disorders and Stroke medical neurology branch and its human motor control section.

New evidence added to the already well-established data on the effectiveness of botulinum toxin for cervical dystonia suggest that onaBoNT-A and incoBoNT-A are probably safe and effective and should be considered. In addition, aboBoNT-A and rimaBoNT-B have already proven effectiveness and safety and should be offered. The lack of class I studies for onaBoNT-A and incoBoNT-A led to the lower level of recommendation for them despite an extensive clinical history of their use in cervical dystonia, the guideline committee wrote (Neurology. 2016 Apr 18. doi: 10.1212/WNL.0000000000002560).

In adults with upper-limb spasticity, all three serotype A formulations – onaBoNT-A, aboBoNT-A, and incoBoNT-A – are effective and safe in reducing symptoms and improving passive limb function. All three achieved level A evidence to recommend that they should be offered. One comparative trial showed enough evidence to say that onaBoNT-A is probably superior to tizanidine for reducing upper-extremity tone and should be considered before it. RimaBoNT-B has level B evidence to advise that it should be considered and is probably safe and effective. None of the formulations have enough data to determine their efficacy on active limb function.

Fewer trials have examined the safety and effectiveness of botulinum toxin formulations for reducing lower leg spasticity in adults. The guidelines panel found enough evidence to recommend that aboBoNT-A and onaBoNT-A are safe and effective and should be offered (level A). There were no trials with high enough level of quality to determine whether incoBoNT-A or rimaBoNT-B were effective for lower-leg spasticity. None of the four agents had enough evidence to support their ability to improve active function associated with lower-limb spasticity.

At the press briefing, guidelines first author Dr. David M. Simpson expressed hope that a more refined methodology for evaluating spasticity might be achieved in future trials of botulinum toxin to detect the potentially subtle effects the agents may have on certain patients who are more likely to achieve benefits in active limb function. Currently, trials use a standardized set of outcomes to try to detect differences in patients with wide-ranging severity of symptoms and types of injury that led to spasticity. Dr. Simpson is professor of neurology at Mount Sinai in New York, as well as director of the neuromuscular diseases division and director of the clinical neurophysiology laboratories.

Positive results for onaBoNT-A in two pivotal trials in chronic migraine that were published since the last guidelines give the formulation the only FDA-approved indication for a botulinum toxin in chronic migraine and earned it a level A recommendation from the guidelines committee. However, in the trials it had a relatively small magnitude of efficacy in reducing the number of headache days by 15% versus placebo. The guidelines also advise not using onaBoNT-A in episodic migraine based on three negative trials. No high-quality trials have evaluated any formulation to change the overall 2008 guidelines’ advice that botulinum toxin is probably ineffective for treating chronic tension-type headaches.

Familiarity with appropriate dosing and side effects may allow clinicians to use the products off-label for indications in the guidelines for which clinical trials were not available, Dr. Richard L. Barbano of the movement disorders division at the University of Rochester noted in an editorial about the guidelines (Neurol Clin Pract. 2016 Apr 18. doi: 10.1212/CPJ.0000000000000244). “Off-label use is common in clinical practice. Little data exist to indicate that any of the different formulations, with attention to appropriate dosing and side effects, would not be effective in treating these other conditions. There are also a number of other neurologic conditions not discussed in the guideline in which botulinum toxin has shown efficacy, such as hemifacial spasm and other focal dystonias. Lack of sufficient high-level evidence to support a level A or B guideline recommendation does not negate their potential utility and likewise, there is little evidence to recommend one formulation over another.”

“In some circumstances where the drugs are relatively equivalent, some people prefer to stick with one so they get used to it more, and they can have more of a sense of what the dosing is, given that the doses may be different with the compounds and have different side effects,” Dr. Hallett said in an interview, noting that availability and price also might enter into a clinician’s decision on what to do.

Dr. Barbano also said that cost and value are becoming more important, and neurologists should consider when botulinum toxin therapy should be chosen among existing alternative treatment options, particularly for chronic migraine.

The guidelines are endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine and the American Society of Plastic Surgeons.

Dr. Hallett reported serving as chair of the Neurotoxin Institute Advisory Council and has received research grants from Allergan and Merz Pharmaceuticals. Dr. Simpson reported receiving research grants from and served as a consultant for Allergan, Ipsen, Merz Pharmaceuticals, and Acorda Therapeutics. Five other coauthors of the guidelines disclosed relationships with manufacturers of botulinum toxin formulations. Dr. Barbano reported serving on a scientific advisory board for Allergan and receiving research support from Allergan, Vaccinex, and Biotie.

[email protected]

VANCOUVER – A new American Academy of Neurology practice guideline on the efficacy and safety evidence for botulinum toxin treatment of blepharospasm, cervical dystonia, spasticity, and headache has updated the last recommendations published in 2008, but leaves some relevant clinical concerns and off-label uses unaddressed.

The 2016 update, published April 18 in Neurology, adds new individual evidence for the use of the four branded formulations of the two commercially available botulinum toxin serotypes, A and B, for the aforementioned indications rather than lumping all recommendations for botulinum toxin together as in the 2008 guidelines. However, questions remain on the differences between the different products in clinical practice, especially since the formulations show little clinical difference in head-to-head comparisons for some of the indications, especially for the serotype A formulations.

Jeff Evans/Frontline Medical News

In a press briefing on the new guidelines at the annual meeting of the American Academy of Neurology, guidelines coauthor Dr. Mark Hallett noted that nothing really surprised the experienced 14-member committee that put the guidelines together. “The reason that we chose these four different diseases is because we already had the sense that they were going to change in the particular ways that they did. We didn’t know exactly, of course, what was going to happen, but we had a sense that there were sufficient data that it was worth looking at them.”

For blepharospasm, the totality of evidence suggests that onabotulinumtoxinA (onaBoNT-A; Botox) and incobotulinumtoxinA (incoBoNT-A; Xeomin) injections should be considered and are probably safe and effective (level B recommendation), while abobotulinumtoxinA (aboBoNT-A; Dysport) may be considered (level C) and is possibly effective. The evidence shows that incoBoNT-A and onaBoNT-A have equivalent efficacy and aboBoNT-A and onaBoNT-A are possibly equivalent. There was not enough evidence to determine the efficacy of rimabotulinumtoxinB for blepharospasm (rimaBoNT-B; Myobloc).

The rigorousness of clinical trials in evaluating the efficacy and safety of botulinum toxin has evolved since the Food and Drug Administration approved onaBoNT-A and incoBoNT-A to treat blepharospasm, but no new trials have been conducted to give it a higher level of recommendation despite their well-known magnitude of benefit, said Dr. Hallett, chief of the National Institute of Neurological Disorders and Stroke medical neurology branch and its human motor control section.

New evidence added to the already well-established data on the effectiveness of botulinum toxin for cervical dystonia suggest that onaBoNT-A and incoBoNT-A are probably safe and effective and should be considered. In addition, aboBoNT-A and rimaBoNT-B have already proven effectiveness and safety and should be offered. The lack of class I studies for onaBoNT-A and incoBoNT-A led to the lower level of recommendation for them despite an extensive clinical history of their use in cervical dystonia, the guideline committee wrote (Neurology. 2016 Apr 18. doi: 10.1212/WNL.0000000000002560).

In adults with upper-limb spasticity, all three serotype A formulations – onaBoNT-A, aboBoNT-A, and incoBoNT-A – are effective and safe in reducing symptoms and improving passive limb function. All three achieved level A evidence to recommend that they should be offered. One comparative trial showed enough evidence to say that onaBoNT-A is probably superior to tizanidine for reducing upper-extremity tone and should be considered before it. RimaBoNT-B has level B evidence to advise that it should be considered and is probably safe and effective. None of the formulations have enough data to determine their efficacy on active limb function.

Fewer trials have examined the safety and effectiveness of botulinum toxin formulations for reducing lower leg spasticity in adults. The guidelines panel found enough evidence to recommend that aboBoNT-A and onaBoNT-A are safe and effective and should be offered (level A). There were no trials with high enough level of quality to determine whether incoBoNT-A or rimaBoNT-B were effective for lower-leg spasticity. None of the four agents had enough evidence to support their ability to improve active function associated with lower-limb spasticity.

At the press briefing, guidelines first author Dr. David M. Simpson expressed hope that a more refined methodology for evaluating spasticity might be achieved in future trials of botulinum toxin to detect the potentially subtle effects the agents may have on certain patients who are more likely to achieve benefits in active limb function. Currently, trials use a standardized set of outcomes to try to detect differences in patients with wide-ranging severity of symptoms and types of injury that led to spasticity. Dr. Simpson is professor of neurology at Mount Sinai in New York, as well as director of the neuromuscular diseases division and director of the clinical neurophysiology laboratories.

Positive results for onaBoNT-A in two pivotal trials in chronic migraine that were published since the last guidelines give the formulation the only FDA-approved indication for a botulinum toxin in chronic migraine and earned it a level A recommendation from the guidelines committee. However, in the trials it had a relatively small magnitude of efficacy in reducing the number of headache days by 15% versus placebo. The guidelines also advise not using onaBoNT-A in episodic migraine based on three negative trials. No high-quality trials have evaluated any formulation to change the overall 2008 guidelines’ advice that botulinum toxin is probably ineffective for treating chronic tension-type headaches.

Familiarity with appropriate dosing and side effects may allow clinicians to use the products off-label for indications in the guidelines for which clinical trials were not available, Dr. Richard L. Barbano of the movement disorders division at the University of Rochester noted in an editorial about the guidelines (Neurol Clin Pract. 2016 Apr 18. doi: 10.1212/CPJ.0000000000000244). “Off-label use is common in clinical practice. Little data exist to indicate that any of the different formulations, with attention to appropriate dosing and side effects, would not be effective in treating these other conditions. There are also a number of other neurologic conditions not discussed in the guideline in which botulinum toxin has shown efficacy, such as hemifacial spasm and other focal dystonias. Lack of sufficient high-level evidence to support a level A or B guideline recommendation does not negate their potential utility and likewise, there is little evidence to recommend one formulation over another.”

“In some circumstances where the drugs are relatively equivalent, some people prefer to stick with one so they get used to it more, and they can have more of a sense of what the dosing is, given that the doses may be different with the compounds and have different side effects,” Dr. Hallett said in an interview, noting that availability and price also might enter into a clinician’s decision on what to do.

Dr. Barbano also said that cost and value are becoming more important, and neurologists should consider when botulinum toxin therapy should be chosen among existing alternative treatment options, particularly for chronic migraine.

The guidelines are endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine and the American Society of Plastic Surgeons.

Dr. Hallett reported serving as chair of the Neurotoxin Institute Advisory Council and has received research grants from Allergan and Merz Pharmaceuticals. Dr. Simpson reported receiving research grants from and served as a consultant for Allergan, Ipsen, Merz Pharmaceuticals, and Acorda Therapeutics. Five other coauthors of the guidelines disclosed relationships with manufacturers of botulinum toxin formulations. Dr. Barbano reported serving on a scientific advisory board for Allergan and receiving research support from Allergan, Vaccinex, and Biotie.

[email protected]

Officials at the Centers for Disease Control and Prevention have determined that Zika virus infection is a cause of microcephaly in babies born to infected mothers, following a systematic review of the latest research on Zika virus.

The CDC released findings from that review in a peer-reviewed special report published online April 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMsr1604338). The report, CDC officials said, incorporated evidence from as recently as the past week.

Sumaia Villela/Agência Brasil/CC BY 3.0 BR

In a press conference in April, CDC director Tom Frieden said there was “no longer any doubt” that Zika virus causes microcephaly. Dr. Frieden’s statements reflect what appears to be a growing scientific consensus. On March 31, the World Health Organization reported that there was a “strong” consensus that Zika virus can cause microcephaly, Guillain-Barré syndrome, and other neurological disorders. New microcephaly cases in Colombia – with 32 reported by the end of March – are among the findings cited by both the WHO and the CDC.

Dr. Frieden stressed that no single piece of evidence was seen to provide conclusive proof of causation, but that the CDC scientists’ conclusions were based on “a thorough review of the best available evidence” subjected to established criteria.

For its review published in the New England Journal of Medicine, CDC scientists led by Dr. Sonja Rasmussen subjected available evidence to two separate criteria to determine the relationship of Zika virus to the spikes in microcephaly cases seen in countries where Zika is spreading. Shepard’s criteria were used to prove teratogenicity, and the Bradford Hill criteria were used to show evidence of causation.

The CDC has not made any changes to its guidance on Zika virus prevention, which includes advising pregnant women to avoid travel to regions where Zika transmission is occurring, take steps to prevent infection if they live in areas where Zika virus is present, and use condoms to prevent sexual transmission of Zika from a partner. On April 13, the CDC added St. Lucia to its growing list of countries to be avoided by pregnant women.

The full spectrum of defects caused by congenital Zika infection is still poorly understood. Additional studies are underway at CDC, Dr. Frieden said, to better understand the severe phenotype of microcephaly seen in babies born to Zika-infected mothers and “to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain.”

Officials at the Centers for Disease Control and Prevention have determined that Zika virus infection is a cause of microcephaly in babies born to infected mothers, following a systematic review of the latest research on Zika virus.

The CDC released findings from that review in a peer-reviewed special report published online April 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMsr1604338). The report, CDC officials said, incorporated evidence from as recently as the past week.

Sumaia Villela/Agência Brasil/CC BY 3.0 BR

In a press conference in April, CDC director Tom Frieden said there was “no longer any doubt” that Zika virus causes microcephaly. Dr. Frieden’s statements reflect what appears to be a growing scientific consensus. On March 31, the World Health Organization reported that there was a “strong” consensus that Zika virus can cause microcephaly, Guillain-Barré syndrome, and other neurological disorders. New microcephaly cases in Colombia – with 32 reported by the end of March – are among the findings cited by both the WHO and the CDC.

Dr. Frieden stressed that no single piece of evidence was seen to provide conclusive proof of causation, but that the CDC scientists’ conclusions were based on “a thorough review of the best available evidence” subjected to established criteria.

For its review published in the New England Journal of Medicine, CDC scientists led by Dr. Sonja Rasmussen subjected available evidence to two separate criteria to determine the relationship of Zika virus to the spikes in microcephaly cases seen in countries where Zika is spreading. Shepard’s criteria were used to prove teratogenicity, and the Bradford Hill criteria were used to show evidence of causation.

The CDC has not made any changes to its guidance on Zika virus prevention, which includes advising pregnant women to avoid travel to regions where Zika transmission is occurring, take steps to prevent infection if they live in areas where Zika virus is present, and use condoms to prevent sexual transmission of Zika from a partner. On April 13, the CDC added St. Lucia to its growing list of countries to be avoided by pregnant women.

The full spectrum of defects caused by congenital Zika infection is still poorly understood. Additional studies are underway at CDC, Dr. Frieden said, to better understand the severe phenotype of microcephaly seen in babies born to Zika-infected mothers and “to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain.”

Officials at the Centers for Disease Control and Prevention have determined that Zika virus infection is a cause of microcephaly in babies born to infected mothers, following a systematic review of the latest research on Zika virus.

The CDC released findings from that review in a peer-reviewed special report published online April 13 in the New England Journal of Medicine (2016. doi: 10.1056/NEJMsr1604338). The report, CDC officials said, incorporated evidence from as recently as the past week.

Sumaia Villela/Agência Brasil/CC BY 3.0 BR

In a press conference in April, CDC director Tom Frieden said there was “no longer any doubt” that Zika virus causes microcephaly. Dr. Frieden’s statements reflect what appears to be a growing scientific consensus. On March 31, the World Health Organization reported that there was a “strong” consensus that Zika virus can cause microcephaly, Guillain-Barré syndrome, and other neurological disorders. New microcephaly cases in Colombia – with 32 reported by the end of March – are among the findings cited by both the WHO and the CDC.

Dr. Frieden stressed that no single piece of evidence was seen to provide conclusive proof of causation, but that the CDC scientists’ conclusions were based on “a thorough review of the best available evidence” subjected to established criteria.

For its review published in the New England Journal of Medicine, CDC scientists led by Dr. Sonja Rasmussen subjected available evidence to two separate criteria to determine the relationship of Zika virus to the spikes in microcephaly cases seen in countries where Zika is spreading. Shepard’s criteria were used to prove teratogenicity, and the Bradford Hill criteria were used to show evidence of causation.

The CDC has not made any changes to its guidance on Zika virus prevention, which includes advising pregnant women to avoid travel to regions where Zika transmission is occurring, take steps to prevent infection if they live in areas where Zika virus is present, and use condoms to prevent sexual transmission of Zika from a partner. On April 13, the CDC added St. Lucia to its growing list of countries to be avoided by pregnant women.

The full spectrum of defects caused by congenital Zika infection is still poorly understood. Additional studies are underway at CDC, Dr. Frieden said, to better understand the severe phenotype of microcephaly seen in babies born to Zika-infected mothers and “to determine whether children who have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what we could see in damaging effects on the brain.”

Patient-controlled epidural analgesia achieves pain control similar to that of patient-controlled intravenous analgesia after spinal fusion surgery, but is associated with a higher incidence of pruritus and paresthesia, a meta-analysis published in BMC Musculoskeletal Disorders has found.

The analysis of eight randomized controlled trials involving 482 patients found that patient-controlled epidural analgesia was associated with significantly better analgesic effects on day 1 and 2 after surgery (mean difference in visual analog scale scores of −0.47 and −0.66, respectively), but this difference was no longer statistically significant on day 3.

Thomas Northcut/ ©Thinkstock

The study, conducted by Dr. Peng Tian of Tianjin (China) Hospital and colleagues showed that patient-controlled epidural analgesia was associated with a significant 53% higher incidence of pruritus and a threefold increase in paresthesia, compared with patient-controlled intravenous analgesia, although there were no significant differences in the rates of nausea or vomiting (BMC Musculoskeletal Disorders 2015 Dec 15. doi: 10.1186/s12891-015-0849-y).

Researchers noted that patient-controlled epidural analgesia achieves a faster analgesic effect than does patient-controlled intravenous analgesia because it acts directly on the near-operative region, but the analgesic effect of the intravenous administration lasts longer.

“The most important findings of the present meta-analysis are that the application of PCEA [patient-controlled epidural analgesia] does not more effectively relieve” pain in 3 postoperative days compared with patient-controlled intravenous analgesia, “meanwhile increasing the incidence of some complications such as pruritus and paresthesia,” wrote the investigators.

The National Natural Science Foundation of China supported the study. No conflicts of interest were declared.

Patient-controlled epidural analgesia achieves pain control similar to that of patient-controlled intravenous analgesia after spinal fusion surgery, but is associated with a higher incidence of pruritus and paresthesia, a meta-analysis published in BMC Musculoskeletal Disorders has found.

The analysis of eight randomized controlled trials involving 482 patients found that patient-controlled epidural analgesia was associated with significantly better analgesic effects on day 1 and 2 after surgery (mean difference in visual analog scale scores of −0.47 and −0.66, respectively), but this difference was no longer statistically significant on day 3.

Thomas Northcut/ ©Thinkstock

The study, conducted by Dr. Peng Tian of Tianjin (China) Hospital and colleagues showed that patient-controlled epidural analgesia was associated with a significant 53% higher incidence of pruritus and a threefold increase in paresthesia, compared with patient-controlled intravenous analgesia, although there were no significant differences in the rates of nausea or vomiting (BMC Musculoskeletal Disorders 2015 Dec 15. doi: 10.1186/s12891-015-0849-y).

Researchers noted that patient-controlled epidural analgesia achieves a faster analgesic effect than does patient-controlled intravenous analgesia because it acts directly on the near-operative region, but the analgesic effect of the intravenous administration lasts longer.

“The most important findings of the present meta-analysis are that the application of PCEA [patient-controlled epidural analgesia] does not more effectively relieve” pain in 3 postoperative days compared with patient-controlled intravenous analgesia, “meanwhile increasing the incidence of some complications such as pruritus and paresthesia,” wrote the investigators.

The National Natural Science Foundation of China supported the study. No conflicts of interest were declared.

Patient-controlled epidural analgesia achieves pain control similar to that of patient-controlled intravenous analgesia after spinal fusion surgery, but is associated with a higher incidence of pruritus and paresthesia, a meta-analysis published in BMC Musculoskeletal Disorders has found.

The analysis of eight randomized controlled trials involving 482 patients found that patient-controlled epidural analgesia was associated with significantly better analgesic effects on day 1 and 2 after surgery (mean difference in visual analog scale scores of −0.47 and −0.66, respectively), but this difference was no longer statistically significant on day 3.

Thomas Northcut/ ©Thinkstock

The study, conducted by Dr. Peng Tian of Tianjin (China) Hospital and colleagues showed that patient-controlled epidural analgesia was associated with a significant 53% higher incidence of pruritus and a threefold increase in paresthesia, compared with patient-controlled intravenous analgesia, although there were no significant differences in the rates of nausea or vomiting (BMC Musculoskeletal Disorders 2015 Dec 15. doi: 10.1186/s12891-015-0849-y).

Researchers noted that patient-controlled epidural analgesia achieves a faster analgesic effect than does patient-controlled intravenous analgesia because it acts directly on the near-operative region, but the analgesic effect of the intravenous administration lasts longer.

“The most important findings of the present meta-analysis are that the application of PCEA [patient-controlled epidural analgesia] does not more effectively relieve” pain in 3 postoperative days compared with patient-controlled intravenous analgesia, “meanwhile increasing the incidence of some complications such as pruritus and paresthesia,” wrote the investigators.

The National Natural Science Foundation of China supported the study. No conflicts of interest were declared.

Sometimes, you come across an article that makes you cringe. After this initial reaction – and if we are up for the challenge – we realize that this information can help us grow by pushing our clinical approach in new directions.

This is the experience I had with an article by Dr. Daniel Bouland and colleagues that explored the ways in which people struggling with addiction obtain prescription medications (J Addict Med. 2015 Jul-Aug;9[4]:281-5).

In this semiquantitative qualitative study, investigators interviewed 36 patients in a residential addiction treatment program who obtained prescriptions from clinicians in support of an addiction. Types of medications obtained by respondents were opioids (97.2%), sedative hypnotics (47.4%), and amphetamines (5.5%).

Patients reported obtaining prescriptions from clinicians because it was perceived to be “legal” – even though 75% of them faked symptoms, several falsified MRI images of an injury, and some used old or forged prescriptions. One patient paid a physician outright for the medication.

Eight percent of patients physically harmed themselves to obtain prescriptions by doing things such as cutting themselves to put blood in the urine, hitting their head against the wall to the point of unconsciousness, and undergoing unnecessary surgery.

Primary care clinicians and pain specialists were viewed as the easiest sources of medication. Most patients used “mom and pop” pharmacies, visited multiple pharmacies, and paid in cash. Importantly, 67% of patients said that an intervention could have changed their behaviors.

I think I knew this, but it challenged me to see it in writing. I appreciated the honesty of these individuals and was struck by the fact that almost two-thirds suggested that an intervention could have transformed them.

But how to start this conversation?

The last time I expressed concern about a patient’s allergy to any pain medication – except oxycodone and the potentially toxic doses of ibuprofen and acetaminophen that didn’t “touch it” – I was the recipient of seething rage and hostility.

Addiction treatment is hard, diagnosing addiction in daily primary care practice is harder, and holding up a mirror to a patient’s prescription drug habits requires protective body armor. That’s why not many of us do it.

So, now that we have guidelines for chronic opioids, we need best practices for acute visits presenting with x-rays of broken animal bones labeled with their name handwritten on duct tape.

Are we up for urine drug screens for every controlled substance prescription on nonestablished patients every time? Probably not, but we have to start somewhere.

At least it might start a conversation when we can say: “We do this for all of our patients, we are not singling you out. Is there anything you would like to talk about before we complete this test?”

Most importantly, once we make a diagnosis of prescription drug abuse, we need resources to which to refer them and health insurance to help cover the cost for this care.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.

Sometimes, you come across an article that makes you cringe. After this initial reaction – and if we are up for the challenge – we realize that this information can help us grow by pushing our clinical approach in new directions.

This is the experience I had with an article by Dr. Daniel Bouland and colleagues that explored the ways in which people struggling with addiction obtain prescription medications (J Addict Med. 2015 Jul-Aug;9[4]:281-5).

In this semiquantitative qualitative study, investigators interviewed 36 patients in a residential addiction treatment program who obtained prescriptions from clinicians in support of an addiction. Types of medications obtained by respondents were opioids (97.2%), sedative hypnotics (47.4%), and amphetamines (5.5%).

Patients reported obtaining prescriptions from clinicians because it was perceived to be “legal” – even though 75% of them faked symptoms, several falsified MRI images of an injury, and some used old or forged prescriptions. One patient paid a physician outright for the medication.

Eight percent of patients physically harmed themselves to obtain prescriptions by doing things such as cutting themselves to put blood in the urine, hitting their head against the wall to the point of unconsciousness, and undergoing unnecessary surgery.

Primary care clinicians and pain specialists were viewed as the easiest sources of medication. Most patients used “mom and pop” pharmacies, visited multiple pharmacies, and paid in cash. Importantly, 67% of patients said that an intervention could have changed their behaviors.

I think I knew this, but it challenged me to see it in writing. I appreciated the honesty of these individuals and was struck by the fact that almost two-thirds suggested that an intervention could have transformed them.

But how to start this conversation?

The last time I expressed concern about a patient’s allergy to any pain medication – except oxycodone and the potentially toxic doses of ibuprofen and acetaminophen that didn’t “touch it” – I was the recipient of seething rage and hostility.

Addiction treatment is hard, diagnosing addiction in daily primary care practice is harder, and holding up a mirror to a patient’s prescription drug habits requires protective body armor. That’s why not many of us do it.

So, now that we have guidelines for chronic opioids, we need best practices for acute visits presenting with x-rays of broken animal bones labeled with their name handwritten on duct tape.

Are we up for urine drug screens for every controlled substance prescription on nonestablished patients every time? Probably not, but we have to start somewhere.

At least it might start a conversation when we can say: “We do this for all of our patients, we are not singling you out. Is there anything you would like to talk about before we complete this test?”

Most importantly, once we make a diagnosis of prescription drug abuse, we need resources to which to refer them and health insurance to help cover the cost for this care.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.

Sometimes, you come across an article that makes you cringe. After this initial reaction – and if we are up for the challenge – we realize that this information can help us grow by pushing our clinical approach in new directions.

This is the experience I had with an article by Dr. Daniel Bouland and colleagues that explored the ways in which people struggling with addiction obtain prescription medications (J Addict Med. 2015 Jul-Aug;9[4]:281-5).

In this semiquantitative qualitative study, investigators interviewed 36 patients in a residential addiction treatment program who obtained prescriptions from clinicians in support of an addiction. Types of medications obtained by respondents were opioids (97.2%), sedative hypnotics (47.4%), and amphetamines (5.5%).

Patients reported obtaining prescriptions from clinicians because it was perceived to be “legal” – even though 75% of them faked symptoms, several falsified MRI images of an injury, and some used old or forged prescriptions. One patient paid a physician outright for the medication.

Eight percent of patients physically harmed themselves to obtain prescriptions by doing things such as cutting themselves to put blood in the urine, hitting their head against the wall to the point of unconsciousness, and undergoing unnecessary surgery.

Primary care clinicians and pain specialists were viewed as the easiest sources of medication. Most patients used “mom and pop” pharmacies, visited multiple pharmacies, and paid in cash. Importantly, 67% of patients said that an intervention could have changed their behaviors.

I think I knew this, but it challenged me to see it in writing. I appreciated the honesty of these individuals and was struck by the fact that almost two-thirds suggested that an intervention could have transformed them.

But how to start this conversation?

The last time I expressed concern about a patient’s allergy to any pain medication – except oxycodone and the potentially toxic doses of ibuprofen and acetaminophen that didn’t “touch it” – I was the recipient of seething rage and hostility.

Addiction treatment is hard, diagnosing addiction in daily primary care practice is harder, and holding up a mirror to a patient’s prescription drug habits requires protective body armor. That’s why not many of us do it.

So, now that we have guidelines for chronic opioids, we need best practices for acute visits presenting with x-rays of broken animal bones labeled with their name handwritten on duct tape.

Are we up for urine drug screens for every controlled substance prescription on nonestablished patients every time? Probably not, but we have to start somewhere.

At least it might start a conversation when we can say: “We do this for all of our patients, we are not singling you out. Is there anything you would like to talk about before we complete this test?”

Most importantly, once we make a diagnosis of prescription drug abuse, we need resources to which to refer them and health insurance to help cover the cost for this care.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.

Many more physicians seeking to subspecialize in addiction medicine will now have the official blessing of the American Board of Medical Specialties.

ABMS announced March 14 its approval of an addiction medicine subspecialty that the American Board of Preventive Medicine (ABPM) will sponsor.

Physicians who are certified by any of the 24 ABMS member boards can apply for the addiction medicine certification. The American Board of Psychiatry and Neurology offers certification in addiction psychiatry, but only to psychiatrists.

ABPM hasn’t set a date for the addiction medicine subspecialty’s first board certification exam, which the board will develop. ABPM will post updates on its website, www.theabpm.org.

“Increasing the number of well-trained and certified specialists in addiction medicine will significantly increase access to care for those in need of intervention and treatment,” said ABPM’s board chair, Dr. Denece O. Kesler, in a statement.

One in seven Americans older than 12 years meets medical criteria for an addiction to nicotine, alcohol, or other drugs, according to statistics from the National Center on Addiction and Substance Abuse. But only 11% of those who need treatment are able to receive it, in part because of a lack of addiction medicine providers.

The American Board of Addiction Medicine (ABAM) hailed the new subspecialty. “This is a great day for addiction medicine,” Dr. Robert J. Sokol, president of ABAM and the Addiction Medicine Foundation (AMF), said in a statement. “This landmark event, more than any other, recognizes addiction as a preventable and treatable disease.”

ABAM has certified 3,902 physicians, according to the organization, which is not an ABMS member board. There are 40 AMF-sponsored fellowship training programs nationally, with a commitment to establish 125 more by 2025. AMF expects the ABMS recognition will lead to the fellowships gaining the imprimatur of the Accreditation Council on Graduate Medical Education.

“This is a positive development that has the potential to address a serious public health problem,” Dr. Daniel Lieberman, vice chairman of the psychiatry and behavioral health department at George Washington University, Washington, said in an interview. “This action will reassure doctors who are interested in addiction medicine that the time and effort they put into obtaining additional training will give them the status of a subspecialist with recognized expertise. It may also encourage young doctors to consider addiction medicine as a career path.”

Meanwhile, a package of mental health reforms moving in the U.S. Senate could improve patients’ access to addiction medicine providers. One of the bills, the TREAT Act, would increase the number of substance use detoxification patients that a qualified provider is legally allowed to treat annually, from 30 patients to 100 patients. The legislation also would allow those practitioners to request permission to annually treat unlimited numbers of patients thereafter.

[email protected]

On Twitter @whitneymcknight

Many more physicians seeking to subspecialize in addiction medicine will now have the official blessing of the American Board of Medical Specialties.

ABMS announced March 14 its approval of an addiction medicine subspecialty that the American Board of Preventive Medicine (ABPM) will sponsor.

Physicians who are certified by any of the 24 ABMS member boards can apply for the addiction medicine certification. The American Board of Psychiatry and Neurology offers certification in addiction psychiatry, but only to psychiatrists.

ABPM hasn’t set a date for the addiction medicine subspecialty’s first board certification exam, which the board will develop. ABPM will post updates on its website, www.theabpm.org.

“Increasing the number of well-trained and certified specialists in addiction medicine will significantly increase access to care for those in need of intervention and treatment,” said ABPM’s board chair, Dr. Denece O. Kesler, in a statement.

One in seven Americans older than 12 years meets medical criteria for an addiction to nicotine, alcohol, or other drugs, according to statistics from the National Center on Addiction and Substance Abuse. But only 11% of those who need treatment are able to receive it, in part because of a lack of addiction medicine providers.

The American Board of Addiction Medicine (ABAM) hailed the new subspecialty. “This is a great day for addiction medicine,” Dr. Robert J. Sokol, president of ABAM and the Addiction Medicine Foundation (AMF), said in a statement. “This landmark event, more than any other, recognizes addiction as a preventable and treatable disease.”

ABAM has certified 3,902 physicians, according to the organization, which is not an ABMS member board. There are 40 AMF-sponsored fellowship training programs nationally, with a commitment to establish 125 more by 2025. AMF expects the ABMS recognition will lead to the fellowships gaining the imprimatur of the Accreditation Council on Graduate Medical Education.

“This is a positive development that has the potential to address a serious public health problem,” Dr. Daniel Lieberman, vice chairman of the psychiatry and behavioral health department at George Washington University, Washington, said in an interview. “This action will reassure doctors who are interested in addiction medicine that the time and effort they put into obtaining additional training will give them the status of a subspecialist with recognized expertise. It may also encourage young doctors to consider addiction medicine as a career path.”

Meanwhile, a package of mental health reforms moving in the U.S. Senate could improve patients’ access to addiction medicine providers. One of the bills, the TREAT Act, would increase the number of substance use detoxification patients that a qualified provider is legally allowed to treat annually, from 30 patients to 100 patients. The legislation also would allow those practitioners to request permission to annually treat unlimited numbers of patients thereafter.

[email protected]

On Twitter @whitneymcknight

Many more physicians seeking to subspecialize in addiction medicine will now have the official blessing of the American Board of Medical Specialties.

ABMS announced March 14 its approval of an addiction medicine subspecialty that the American Board of Preventive Medicine (ABPM) will sponsor.

Physicians who are certified by any of the 24 ABMS member boards can apply for the addiction medicine certification. The American Board of Psychiatry and Neurology offers certification in addiction psychiatry, but only to psychiatrists.

ABPM hasn’t set a date for the addiction medicine subspecialty’s first board certification exam, which the board will develop. ABPM will post updates on its website, www.theabpm.org.

“Increasing the number of well-trained and certified specialists in addiction medicine will significantly increase access to care for those in need of intervention and treatment,” said ABPM’s board chair, Dr. Denece O. Kesler, in a statement.

One in seven Americans older than 12 years meets medical criteria for an addiction to nicotine, alcohol, or other drugs, according to statistics from the National Center on Addiction and Substance Abuse. But only 11% of those who need treatment are able to receive it, in part because of a lack of addiction medicine providers.

The American Board of Addiction Medicine (ABAM) hailed the new subspecialty. “This is a great day for addiction medicine,” Dr. Robert J. Sokol, president of ABAM and the Addiction Medicine Foundation (AMF), said in a statement. “This landmark event, more than any other, recognizes addiction as a preventable and treatable disease.”

ABAM has certified 3,902 physicians, according to the organization, which is not an ABMS member board. There are 40 AMF-sponsored fellowship training programs nationally, with a commitment to establish 125 more by 2025. AMF expects the ABMS recognition will lead to the fellowships gaining the imprimatur of the Accreditation Council on Graduate Medical Education.

“This is a positive development that has the potential to address a serious public health problem,” Dr. Daniel Lieberman, vice chairman of the psychiatry and behavioral health department at George Washington University, Washington, said in an interview. “This action will reassure doctors who are interested in addiction medicine that the time and effort they put into obtaining additional training will give them the status of a subspecialist with recognized expertise. It may also encourage young doctors to consider addiction medicine as a career path.”

Meanwhile, a package of mental health reforms moving in the U.S. Senate could improve patients’ access to addiction medicine providers. One of the bills, the TREAT Act, would increase the number of substance use detoxification patients that a qualified provider is legally allowed to treat annually, from 30 patients to 100 patients. The legislation also would allow those practitioners to request permission to annually treat unlimited numbers of patients thereafter.

[email protected]

On Twitter @whitneymcknight

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 today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline 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 U.S. 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. 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.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

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 – 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 nonpharmacologic 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, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

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 today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline 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 U.S. 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. 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.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

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 – 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 nonpharmacologic 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, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

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 today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline 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 U.S. 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. 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.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

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 – 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 nonpharmacologic 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, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Serological evidence from French Polynesia links an outbreak of Zika virus to a spike in cases of Guillain-Barré syndrome seen there in 2013-2014.

The research, published online Feb. 29 in The Lancet, is the first to use a case-control design to demonstrate that Zika, a mosquito-borne flavivirus, is associated with Guillain-Barré syndrome (Lancet. 2016 Feb 29. doi: 10.1016/S0140-6736(16)00562-6).

Guillain-Barré syndrome (GBS) is an immune-mediated flaccid paralysis that can follow viral or bacterial infections. Most patients with GBS recover with intensive care in hospitals, although the syndrome can be permanently debilitating or, in rare cases, fatal.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

As a large outbreak of Zika continues in Central and South America, hospitals should be prepared for excess GBS cases, the authors of the study say, and assure adequate intensive-care capacity to treat them. Based on the 66% attack rate of Zika during the French Polynesia outbreak, investigators estimated the incidence of GBS at 0.24 per 1,000 Zika infections, but noted that it could be different in the current outbreak.

Dr. Van-Mai Cao-Lormeau of the Unit of Emerging Infectious Diseases at Institut Louis Malardé in Papeete, French Polynesia, alongside colleagues in France and French Polynesia, used a case-control design to compare serological samples from 42 patients (74% male) diagnosed at a Tahiti hospital with GBS with samples from age-and sex-matched patients who presented at the same hospital, also during the time of the outbreak, with a nonfebrile illness (n = 98) or with acute Zika disease without neurological symptoms (n = 70).

The investigators found that all but one patient with GBS had Zika virus antibodies, and all of them had neutralizing antibodies to Zika virus. By comparison, only 56% (n = 54) of the control group admitted with nonfebrile illness had neutralizing antibodies (P less than .0001).

Also, 93% of the GBS patients had Zika virus immunoglobulin M (IgM) and 88% reported symptoms consistent with Zika infection a mean of 6 days before onset of neurological symptoms. Acute Zika infection is usually characterized by rash, fever, and conjunctivitis.

Past dengue virus infection, which had been considered a possible risk factor for Zika-mediated GBS, did not differ significantly between patients in the control groups and those with GBS.

The investigators were also able to subtype the clinical characteristics of the GBS cases as consistent with acute motor axonal neuropathy, or AMAN, phenotype. However, the antibodies typically seen associated with AMAN were not seen in these patients, leading investigators to suspect that a different biological pathway was responsible.

More than a third of the GBS patients in the study required intensive care, most of these also with respiratory support, though none died.

The government of France, the European Union, and the Wellcome Trust funded the study. The researchers declared that they had no competing interests.

Serological evidence from French Polynesia links an outbreak of Zika virus to a spike in cases of Guillain-Barré syndrome seen there in 2013-2014.

The research, published online Feb. 29 in The Lancet, is the first to use a case-control design to demonstrate that Zika, a mosquito-borne flavivirus, is associated with Guillain-Barré syndrome (Lancet. 2016 Feb 29. doi: 10.1016/S0140-6736(16)00562-6).

Guillain-Barré syndrome (GBS) is an immune-mediated flaccid paralysis that can follow viral or bacterial infections. Most patients with GBS recover with intensive care in hospitals, although the syndrome can be permanently debilitating or, in rare cases, fatal.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

As a large outbreak of Zika continues in Central and South America, hospitals should be prepared for excess GBS cases, the authors of the study say, and assure adequate intensive-care capacity to treat them. Based on the 66% attack rate of Zika during the French Polynesia outbreak, investigators estimated the incidence of GBS at 0.24 per 1,000 Zika infections, but noted that it could be different in the current outbreak.

Dr. Van-Mai Cao-Lormeau of the Unit of Emerging Infectious Diseases at Institut Louis Malardé in Papeete, French Polynesia, alongside colleagues in France and French Polynesia, used a case-control design to compare serological samples from 42 patients (74% male) diagnosed at a Tahiti hospital with GBS with samples from age-and sex-matched patients who presented at the same hospital, also during the time of the outbreak, with a nonfebrile illness (n = 98) or with acute Zika disease without neurological symptoms (n = 70).

The investigators found that all but one patient with GBS had Zika virus antibodies, and all of them had neutralizing antibodies to Zika virus. By comparison, only 56% (n = 54) of the control group admitted with nonfebrile illness had neutralizing antibodies (P less than .0001).

Also, 93% of the GBS patients had Zika virus immunoglobulin M (IgM) and 88% reported symptoms consistent with Zika infection a mean of 6 days before onset of neurological symptoms. Acute Zika infection is usually characterized by rash, fever, and conjunctivitis.

Past dengue virus infection, which had been considered a possible risk factor for Zika-mediated GBS, did not differ significantly between patients in the control groups and those with GBS.

The investigators were also able to subtype the clinical characteristics of the GBS cases as consistent with acute motor axonal neuropathy, or AMAN, phenotype. However, the antibodies typically seen associated with AMAN were not seen in these patients, leading investigators to suspect that a different biological pathway was responsible.

More than a third of the GBS patients in the study required intensive care, most of these also with respiratory support, though none died.

The government of France, the European Union, and the Wellcome Trust funded the study. The researchers declared that they had no competing interests.

Serological evidence from French Polynesia links an outbreak of Zika virus to a spike in cases of Guillain-Barré syndrome seen there in 2013-2014.

The research, published online Feb. 29 in The Lancet, is the first to use a case-control design to demonstrate that Zika, a mosquito-borne flavivirus, is associated with Guillain-Barré syndrome (Lancet. 2016 Feb 29. doi: 10.1016/S0140-6736(16)00562-6).

Guillain-Barré syndrome (GBS) is an immune-mediated flaccid paralysis that can follow viral or bacterial infections. Most patients with GBS recover with intensive care in hospitals, although the syndrome can be permanently debilitating or, in rare cases, fatal.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

As a large outbreak of Zika continues in Central and South America, hospitals should be prepared for excess GBS cases, the authors of the study say, and assure adequate intensive-care capacity to treat them. Based on the 66% attack rate of Zika during the French Polynesia outbreak, investigators estimated the incidence of GBS at 0.24 per 1,000 Zika infections, but noted that it could be different in the current outbreak.

Dr. Van-Mai Cao-Lormeau of the Unit of Emerging Infectious Diseases at Institut Louis Malardé in Papeete, French Polynesia, alongside colleagues in France and French Polynesia, used a case-control design to compare serological samples from 42 patients (74% male) diagnosed at a Tahiti hospital with GBS with samples from age-and sex-matched patients who presented at the same hospital, also during the time of the outbreak, with a nonfebrile illness (n = 98) or with acute Zika disease without neurological symptoms (n = 70).

The investigators found that all but one patient with GBS had Zika virus antibodies, and all of them had neutralizing antibodies to Zika virus. By comparison, only 56% (n = 54) of the control group admitted with nonfebrile illness had neutralizing antibodies (P less than .0001).

Also, 93% of the GBS patients had Zika virus immunoglobulin M (IgM) and 88% reported symptoms consistent with Zika infection a mean of 6 days before onset of neurological symptoms. Acute Zika infection is usually characterized by rash, fever, and conjunctivitis.

Past dengue virus infection, which had been considered a possible risk factor for Zika-mediated GBS, did not differ significantly between patients in the control groups and those with GBS.

The investigators were also able to subtype the clinical characteristics of the GBS cases as consistent with acute motor axonal neuropathy, or AMAN, phenotype. However, the antibodies typically seen associated with AMAN were not seen in these patients, leading investigators to suspect that a different biological pathway was responsible.

More than a third of the GBS patients in the study required intensive care, most of these also with respiratory support, though none died.

The government of France, the European Union, and the Wellcome Trust funded the study. The researchers declared that they had no competing interests.

A consensus study of the scientific underpinnings of human gene editing technologies is underway, and the committee of experts behind the effort will independently review potential applications for those technologies, as well as the clinical, ethical, legal, and social implications of their use.

The multidisciplinary committee met Feb. 11 to receive input from select stakeholders as it launches its review, the results of which will represent the official views of the National Academy of Sciences and the National Academy of Medicine.

©Thinkstock.com

Among those stakeholders were representatives from several companies commercializing gene editing, a representative from the National Institutes of Health, and patient advocacy groups.

With some caveats, participants lobbied to maintain the existing regulatory framework related to gene therapy.

Michael Werner, cofounder and executive director of the Alliance for Regenerative Medicine, which advocates globally for regenerative medicine and advanced therapies, said his organization believes “the existing regulatory framework overall works for these technologies.”

“We don’t believe the [Food and Drug Administration], for example, needs to create a whole separate oversight process in addition to the process we already have now for gene therapy,” he said, adding that “the ultimate goal here is not to have regulatory action or legislative action that will hinder or delay the development of these technologies.”

The consensus study follows an International Summit on Human Gene Editing held in December, and is the next component of the Human Gene Editing Initiative. The committee will study the potential for gene editing in biomedical research and medicine – including human germline editing – although representatives from each of the companies represented at the meeting noted that they are not currently focused on germline applications.

Rather, the commercial focus is on other areas, such as correcting genes in somatic cells.

“We start with medical need. We want to work on things where there is not currently a therapy that addresses adequately the medical need, and we need the ability to generate a differentiated product,” said Vic Myer, Ph.D., of Editas Medicine in Cambridge, Mass.

The company has projects underway for opthalmologic applications, sickle cell anemia, beta-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, alpha₁-antitrypsin deficiency in the liver, and others.

“We are working on a number of different types of edits in a number of different tissues with a number of delivery modalities,” Dr. Myer said, noting that some programs will move quickly, while others will not.

Similarly, Intellia Therapeutics, also of Cambridge, Mass., is “focusing very much on what we hope will be curative products for somatic gene-based disorders,” said Dr. John Leonard, the company’s chief medical officer.

“We limit our work to somatic cells. We thought very carefully about that and that is what we do,” he added, noting that a recently launched division of Intellia is focused on autoimmune oncology opportunities (ex vivo), and on liver disease (in vivo).

The committee of experts conducting the consensus study, which began its information-gathering process in December at the International Summit on Human Gene Editing, will take these and other views expressed at the meeting into consideration during its work over the next year. The study will include a literature review and data gathering via meetings in the United States and abroad. The committee will continue to seek input from researchers, clinicians, policy makers, and the public.

“The committee will also monitor in real time the latest scientific achievements of importance in this rapidly developing field,” according to information from the National Academies.

The field has enormous potential, according to Mr. Werner, who explained that combined, the various types of gene editing technology available are “pretty powerful” in terms of an approach for targeting and changing DNA sequences in human cells.

“We’re talking about the potential to durably treat and potentially even cure diseases that currently represent unmet medical needs,” he said. “We could, in theory, be talking about millions of patients worldwide.”

[email protected]

A consensus study of the scientific underpinnings of human gene editing technologies is underway, and the committee of experts behind the effort will independently review potential applications for those technologies, as well as the clinical, ethical, legal, and social implications of their use.

The multidisciplinary committee met Feb. 11 to receive input from select stakeholders as it launches its review, the results of which will represent the official views of the National Academy of Sciences and the National Academy of Medicine.

©Thinkstock.com

Among those stakeholders were representatives from several companies commercializing gene editing, a representative from the National Institutes of Health, and patient advocacy groups.

With some caveats, participants lobbied to maintain the existing regulatory framework related to gene therapy.

Michael Werner, cofounder and executive director of the Alliance for Regenerative Medicine, which advocates globally for regenerative medicine and advanced therapies, said his organization believes “the existing regulatory framework overall works for these technologies.”

“We don’t believe the [Food and Drug Administration], for example, needs to create a whole separate oversight process in addition to the process we already have now for gene therapy,” he said, adding that “the ultimate goal here is not to have regulatory action or legislative action that will hinder or delay the development of these technologies.”

The consensus study follows an International Summit on Human Gene Editing held in December, and is the next component of the Human Gene Editing Initiative. The committee will study the potential for gene editing in biomedical research and medicine – including human germline editing – although representatives from each of the companies represented at the meeting noted that they are not currently focused on germline applications.

Rather, the commercial focus is on other areas, such as correcting genes in somatic cells.

“We start with medical need. We want to work on things where there is not currently a therapy that addresses adequately the medical need, and we need the ability to generate a differentiated product,” said Vic Myer, Ph.D., of Editas Medicine in Cambridge, Mass.

The company has projects underway for opthalmologic applications, sickle cell anemia, beta-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, alpha₁-antitrypsin deficiency in the liver, and others.

“We are working on a number of different types of edits in a number of different tissues with a number of delivery modalities,” Dr. Myer said, noting that some programs will move quickly, while others will not.

Similarly, Intellia Therapeutics, also of Cambridge, Mass., is “focusing very much on what we hope will be curative products for somatic gene-based disorders,” said Dr. John Leonard, the company’s chief medical officer.

“We limit our work to somatic cells. We thought very carefully about that and that is what we do,” he added, noting that a recently launched division of Intellia is focused on autoimmune oncology opportunities (ex vivo), and on liver disease (in vivo).

The committee of experts conducting the consensus study, which began its information-gathering process in December at the International Summit on Human Gene Editing, will take these and other views expressed at the meeting into consideration during its work over the next year. The study will include a literature review and data gathering via meetings in the United States and abroad. The committee will continue to seek input from researchers, clinicians, policy makers, and the public.

“The committee will also monitor in real time the latest scientific achievements of importance in this rapidly developing field,” according to information from the National Academies.

The field has enormous potential, according to Mr. Werner, who explained that combined, the various types of gene editing technology available are “pretty powerful” in terms of an approach for targeting and changing DNA sequences in human cells.

“We’re talking about the potential to durably treat and potentially even cure diseases that currently represent unmet medical needs,” he said. “We could, in theory, be talking about millions of patients worldwide.”

[email protected]

A consensus study of the scientific underpinnings of human gene editing technologies is underway, and the committee of experts behind the effort will independently review potential applications for those technologies, as well as the clinical, ethical, legal, and social implications of their use.

The multidisciplinary committee met Feb. 11 to receive input from select stakeholders as it launches its review, the results of which will represent the official views of the National Academy of Sciences and the National Academy of Medicine.

©Thinkstock.com

Among those stakeholders were representatives from several companies commercializing gene editing, a representative from the National Institutes of Health, and patient advocacy groups.

With some caveats, participants lobbied to maintain the existing regulatory framework related to gene therapy.

Michael Werner, cofounder and executive director of the Alliance for Regenerative Medicine, which advocates globally for regenerative medicine and advanced therapies, said his organization believes “the existing regulatory framework overall works for these technologies.”

“We don’t believe the [Food and Drug Administration], for example, needs to create a whole separate oversight process in addition to the process we already have now for gene therapy,” he said, adding that “the ultimate goal here is not to have regulatory action or legislative action that will hinder or delay the development of these technologies.”

The consensus study follows an International Summit on Human Gene Editing held in December, and is the next component of the Human Gene Editing Initiative. The committee will study the potential for gene editing in biomedical research and medicine – including human germline editing – although representatives from each of the companies represented at the meeting noted that they are not currently focused on germline applications.

Rather, the commercial focus is on other areas, such as correcting genes in somatic cells.

“We start with medical need. We want to work on things where there is not currently a therapy that addresses adequately the medical need, and we need the ability to generate a differentiated product,” said Vic Myer, Ph.D., of Editas Medicine in Cambridge, Mass.

The company has projects underway for opthalmologic applications, sickle cell anemia, beta-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, alpha₁-antitrypsin deficiency in the liver, and others.

“We are working on a number of different types of edits in a number of different tissues with a number of delivery modalities,” Dr. Myer said, noting that some programs will move quickly, while others will not.

Similarly, Intellia Therapeutics, also of Cambridge, Mass., is “focusing very much on what we hope will be curative products for somatic gene-based disorders,” said Dr. John Leonard, the company’s chief medical officer.

“We limit our work to somatic cells. We thought very carefully about that and that is what we do,” he added, noting that a recently launched division of Intellia is focused on autoimmune oncology opportunities (ex vivo), and on liver disease (in vivo).

The committee of experts conducting the consensus study, which began its information-gathering process in December at the International Summit on Human Gene Editing, will take these and other views expressed at the meeting into consideration during its work over the next year. The study will include a literature review and data gathering via meetings in the United States and abroad. The committee will continue to seek input from researchers, clinicians, policy makers, and the public.

“The committee will also monitor in real time the latest scientific achievements of importance in this rapidly developing field,” according to information from the National Academies.

The field has enormous potential, according to Mr. Werner, who explained that combined, the various types of gene editing technology available are “pretty powerful” in terms of an approach for targeting and changing DNA sequences in human cells.

“We’re talking about the potential to durably treat and potentially even cure diseases that currently represent unmet medical needs,” he said. “We could, in theory, be talking about millions of patients worldwide.”

[email protected]

Clonal immunoglobulin reactive to lyso-glucosylceramide (LGL1), which is elevated in Gaucher disease, was found in patients with Gaucher disease as well as in one third of patients with sporadic monoclonal gammopathies.

Antigen-specific immunoblots showed that 17 of 20 patients with Gaucher disease had clonal immunoglobulin against LGL1, researchers reported (N Engl J Med. 2016 Feb 10).

Analysis of immunoglobulin gene mutations has provided evidence for antigen-driven clonal expansion of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), but the underlying antigens remained unknown. Myeloma risk is increased with lipid disorders such as Gaucher disease and obesity, suggesting lipid involvement in pathogenesis.

“These studies set the stage for newer approaches to lower the levels of these lipids in patients with Gaucher disease and others with precursors for myeloma. Potentially, this could be achieved with drugs or lifestyle changes to reduce the levels of lipids to lower the risk of cancer,” senior author Dr. Madhav Dhodapkar, chief of hematology at Yale Cancer Center, New Haven, Conn., said in a press release.

All six mouse models with Gaucher-like disease had clonal immunoglobulin against LGL1. Gaucher disease–associated gammopathy in mouse models can be targeted by the reduction of the underlying antigen. Feeding eliglustat to the mice with clonal immunoglobulins reduced anti-LGL1 antibodies detected by immunoblot and reduced clonal immunoglobulin in vivo.

Dysregulated lipids are sometimes present in sporadic myeloma, and M spikes on LGL1-specific blotting were LGL1-reactive in 22 of 66 patients (33%). These clonal immunoglobulins also were cross reactive to lysophosphatidylcholine. Patients with polyclonal gammopathies not associated with Gaucher disease did not react to the lysolipids.

“Understanding the antigenic reactivity of clonal immunoglobulin not only has direct implications for antigenic origins of myeloma but also may lead to new strategies to prevent or treat clinical cancer by targeting the underlying antigen,” wrote Shiny Nair, Ph.D., of Yale University and colleagues.

Clonal immunoglobulin reactive to lyso-glucosylceramide (LGL1), which is elevated in Gaucher disease, was found in patients with Gaucher disease as well as in one third of patients with sporadic monoclonal gammopathies.

Antigen-specific immunoblots showed that 17 of 20 patients with Gaucher disease had clonal immunoglobulin against LGL1, researchers reported (N Engl J Med. 2016 Feb 10).

Analysis of immunoglobulin gene mutations has provided evidence for antigen-driven clonal expansion of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), but the underlying antigens remained unknown. Myeloma risk is increased with lipid disorders such as Gaucher disease and obesity, suggesting lipid involvement in pathogenesis.

“These studies set the stage for newer approaches to lower the levels of these lipids in patients with Gaucher disease and others with precursors for myeloma. Potentially, this could be achieved with drugs or lifestyle changes to reduce the levels of lipids to lower the risk of cancer,” senior author Dr. Madhav Dhodapkar, chief of hematology at Yale Cancer Center, New Haven, Conn., said in a press release.

All six mouse models with Gaucher-like disease had clonal immunoglobulin against LGL1. Gaucher disease–associated gammopathy in mouse models can be targeted by the reduction of the underlying antigen. Feeding eliglustat to the mice with clonal immunoglobulins reduced anti-LGL1 antibodies detected by immunoblot and reduced clonal immunoglobulin in vivo.

Dysregulated lipids are sometimes present in sporadic myeloma, and M spikes on LGL1-specific blotting were LGL1-reactive in 22 of 66 patients (33%). These clonal immunoglobulins also were cross reactive to lysophosphatidylcholine. Patients with polyclonal gammopathies not associated with Gaucher disease did not react to the lysolipids.

“Understanding the antigenic reactivity of clonal immunoglobulin not only has direct implications for antigenic origins of myeloma but also may lead to new strategies to prevent or treat clinical cancer by targeting the underlying antigen,” wrote Shiny Nair, Ph.D., of Yale University and colleagues.

Clonal immunoglobulin reactive to lyso-glucosylceramide (LGL1), which is elevated in Gaucher disease, was found in patients with Gaucher disease as well as in one third of patients with sporadic monoclonal gammopathies.

Antigen-specific immunoblots showed that 17 of 20 patients with Gaucher disease had clonal immunoglobulin against LGL1, researchers reported (N Engl J Med. 2016 Feb 10).

Analysis of immunoglobulin gene mutations has provided evidence for antigen-driven clonal expansion of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), but the underlying antigens remained unknown. Myeloma risk is increased with lipid disorders such as Gaucher disease and obesity, suggesting lipid involvement in pathogenesis.

“These studies set the stage for newer approaches to lower the levels of these lipids in patients with Gaucher disease and others with precursors for myeloma. Potentially, this could be achieved with drugs or lifestyle changes to reduce the levels of lipids to lower the risk of cancer,” senior author Dr. Madhav Dhodapkar, chief of hematology at Yale Cancer Center, New Haven, Conn., said in a press release.

All six mouse models with Gaucher-like disease had clonal immunoglobulin against LGL1. Gaucher disease–associated gammopathy in mouse models can be targeted by the reduction of the underlying antigen. Feeding eliglustat to the mice with clonal immunoglobulins reduced anti-LGL1 antibodies detected by immunoblot and reduced clonal immunoglobulin in vivo.

Dysregulated lipids are sometimes present in sporadic myeloma, and M spikes on LGL1-specific blotting were LGL1-reactive in 22 of 66 patients (33%). These clonal immunoglobulins also were cross reactive to lysophosphatidylcholine. Patients with polyclonal gammopathies not associated with Gaucher disease did not react to the lysolipids.

“Understanding the antigenic reactivity of clonal immunoglobulin not only has direct implications for antigenic origins of myeloma but also may lead to new strategies to prevent or treat clinical cancer by targeting the underlying antigen,” wrote Shiny Nair, Ph.D., of Yale University and colleagues.

A test for ocular vestibular evoked myogenic potentials (oVEMP) had a sensitivity of 89% and a specificity of 64% for detecting myasthenia gravis (MG), according to a case-control study of 55 adults published online in Neurology.

“The presence of an oVEMP decrement is a sensitive and specific marker for MG,” said Dr. Yulia Valko at University Hospital Zurich in Switzerland and her associates. “This test allows direct and noninvasive examination of extraocular muscle activity, with similarly good diagnostic accuracy in ocular and generalized MG.”

Myasthenia gravis usually manifests first in the eyes, and early diagnosis and treatment can limit generalization. But nearly half of patients remain undiagnosed a year after onset, partly because standard tests often fail to detect isolated ocular MG, the researchers noted. The recently developed oVEMP test directly measures the activity of the extraocular inferior oblique muscle in response to repeated bursts of vibratory stimulation to the forehead. A decreased response, or decrement, indicates failed neuromuscular transmission, as with standard repetitive nerve stimulation. The researchers evaluated the test in 13 patients with isolated ocular MG, 14 patients with generalized MG, and 28 healthy controls. They defined the oVEMP decrement as the decrease between the second stimulus and the average of the fifth through ninth stimuli (Neurology. 2016 Jan 20. doi: 10.1212/WNL.0000000000002383).

A repetition rate of 20 Hz best differentiated between cases (average decrement, –21.5% plus or minus 29.6%) and controls (–2.8% plus or minus 16.9%), the researchers reported. When at least one eye showed a decrement, the ideal cutoff was a drop of at least 15.2%, which detected MG with a sensitivity of 89% and a sensitivity of 64%. When both eyes were affected, the ideal cutoff for the smallest of the two decrements was at least 20.4%, which yielded a sensitivity of 100% and a specificity of 63%. For both cutoffs, the test was similarly sensitive for detecting ocular and generalized MG, the investigators noted. For the unilateral cutoff, the sensitivity was 92% for patients with isolated ocular MG and 86% for patients with generalized MG. For the bilateral cutoff, specificity was 62% in ocular MG and 64% in generalized MG.

The results provide class III evidence that oVEMP can distinguish between patients with MG and healthy controls, “but future studies will need to confirm its diagnostic utility in clinical practice, where the main challenge is differentiation from patients with other neuro-opthalmologic conditions,” the researchers said. “The possibility to apply fast repetition rates is one important advantage of oVEMP, which is not possible by measuring voluntary saccadic eye movements. As a consequence, oVEMP allowed us to unmask myasthenic decrements even in clinically asymptomatic eyes,” they added.

Because the study used a confirmed diagnosis of MG as a benchmark, all patients were already being treated with cholinesterase inhibitors, the investigators noted. Although they underwent oVEMP testing in the morning before their first dose of medication, the test needs further study in drug-naïve patients, as well as in patients with worse limitations in their upward gaze, they added.

The study was funded by the University of Zurich, the Betty and David Koetser Foundation for Brain Research, the Albert Bruppacher Foundation for Eye Research, and the OPOS Foundation. The investigators had no relevant disclosures.

A test for ocular vestibular evoked myogenic potentials (oVEMP) had a sensitivity of 89% and a specificity of 64% for detecting myasthenia gravis (MG), according to a case-control study of 55 adults published online in Neurology.

“The presence of an oVEMP decrement is a sensitive and specific marker for MG,” said Dr. Yulia Valko at University Hospital Zurich in Switzerland and her associates. “This test allows direct and noninvasive examination of extraocular muscle activity, with similarly good diagnostic accuracy in ocular and generalized MG.”

Myasthenia gravis usually manifests first in the eyes, and early diagnosis and treatment can limit generalization. But nearly half of patients remain undiagnosed a year after onset, partly because standard tests often fail to detect isolated ocular MG, the researchers noted. The recently developed oVEMP test directly measures the activity of the extraocular inferior oblique muscle in response to repeated bursts of vibratory stimulation to the forehead. A decreased response, or decrement, indicates failed neuromuscular transmission, as with standard repetitive nerve stimulation. The researchers evaluated the test in 13 patients with isolated ocular MG, 14 patients with generalized MG, and 28 healthy controls. They defined the oVEMP decrement as the decrease between the second stimulus and the average of the fifth through ninth stimuli (Neurology. 2016 Jan 20. doi: 10.1212/WNL.0000000000002383).

A repetition rate of 20 Hz best differentiated between cases (average decrement, –21.5% plus or minus 29.6%) and controls (–2.8% plus or minus 16.9%), the researchers reported. When at least one eye showed a decrement, the ideal cutoff was a drop of at least 15.2%, which detected MG with a sensitivity of 89% and a sensitivity of 64%. When both eyes were affected, the ideal cutoff for the smallest of the two decrements was at least 20.4%, which yielded a sensitivity of 100% and a specificity of 63%. For both cutoffs, the test was similarly sensitive for detecting ocular and generalized MG, the investigators noted. For the unilateral cutoff, the sensitivity was 92% for patients with isolated ocular MG and 86% for patients with generalized MG. For the bilateral cutoff, specificity was 62% in ocular MG and 64% in generalized MG.

The results provide class III evidence that oVEMP can distinguish between patients with MG and healthy controls, “but future studies will need to confirm its diagnostic utility in clinical practice, where the main challenge is differentiation from patients with other neuro-opthalmologic conditions,” the researchers said. “The possibility to apply fast repetition rates is one important advantage of oVEMP, which is not possible by measuring voluntary saccadic eye movements. As a consequence, oVEMP allowed us to unmask myasthenic decrements even in clinically asymptomatic eyes,” they added.

Because the study used a confirmed diagnosis of MG as a benchmark, all patients were already being treated with cholinesterase inhibitors, the investigators noted. Although they underwent oVEMP testing in the morning before their first dose of medication, the test needs further study in drug-naïve patients, as well as in patients with worse limitations in their upward gaze, they added.

The study was funded by the University of Zurich, the Betty and David Koetser Foundation for Brain Research, the Albert Bruppacher Foundation for Eye Research, and the OPOS Foundation. The investigators had no relevant disclosures.

A test for ocular vestibular evoked myogenic potentials (oVEMP) had a sensitivity of 89% and a specificity of 64% for detecting myasthenia gravis (MG), according to a case-control study of 55 adults published online in Neurology.

“The presence of an oVEMP decrement is a sensitive and specific marker for MG,” said Dr. Yulia Valko at University Hospital Zurich in Switzerland and her associates. “This test allows direct and noninvasive examination of extraocular muscle activity, with similarly good diagnostic accuracy in ocular and generalized MG.”

Myasthenia gravis usually manifests first in the eyes, and early diagnosis and treatment can limit generalization. But nearly half of patients remain undiagnosed a year after onset, partly because standard tests often fail to detect isolated ocular MG, the researchers noted. The recently developed oVEMP test directly measures the activity of the extraocular inferior oblique muscle in response to repeated bursts of vibratory stimulation to the forehead. A decreased response, or decrement, indicates failed neuromuscular transmission, as with standard repetitive nerve stimulation. The researchers evaluated the test in 13 patients with isolated ocular MG, 14 patients with generalized MG, and 28 healthy controls. They defined the oVEMP decrement as the decrease between the second stimulus and the average of the fifth through ninth stimuli (Neurology. 2016 Jan 20. doi: 10.1212/WNL.0000000000002383).

A repetition rate of 20 Hz best differentiated between cases (average decrement, –21.5% plus or minus 29.6%) and controls (–2.8% plus or minus 16.9%), the researchers reported. When at least one eye showed a decrement, the ideal cutoff was a drop of at least 15.2%, which detected MG with a sensitivity of 89% and a sensitivity of 64%. When both eyes were affected, the ideal cutoff for the smallest of the two decrements was at least 20.4%, which yielded a sensitivity of 100% and a specificity of 63%. For both cutoffs, the test was similarly sensitive for detecting ocular and generalized MG, the investigators noted. For the unilateral cutoff, the sensitivity was 92% for patients with isolated ocular MG and 86% for patients with generalized MG. For the bilateral cutoff, specificity was 62% in ocular MG and 64% in generalized MG.

The results provide class III evidence that oVEMP can distinguish between patients with MG and healthy controls, “but future studies will need to confirm its diagnostic utility in clinical practice, where the main challenge is differentiation from patients with other neuro-opthalmologic conditions,” the researchers said. “The possibility to apply fast repetition rates is one important advantage of oVEMP, which is not possible by measuring voluntary saccadic eye movements. As a consequence, oVEMP allowed us to unmask myasthenic decrements even in clinically asymptomatic eyes,” they added.

Because the study used a confirmed diagnosis of MG as a benchmark, all patients were already being treated with cholinesterase inhibitors, the investigators noted. Although they underwent oVEMP testing in the morning before their first dose of medication, the test needs further study in drug-naïve patients, as well as in patients with worse limitations in their upward gaze, they added.

The study was funded by the University of Zurich, the Betty and David Koetser Foundation for Brain Research, the Albert Bruppacher Foundation for Eye Research, and the OPOS Foundation. The investigators had no relevant disclosures.